Adipocyte-secreted extracellular vesicles(EVs)and adipose-derived stem cells(ADSCs)regulate physiological and pathological processes by delivering nucleic acids,proteins,and lipids.Both adipocyte-and ADSC-derived EVs ...Adipocyte-secreted extracellular vesicles(EVs)and adipose-derived stem cells(ADSCs)regulate physiological and pathological processes by delivering nucleic acids,proteins,and lipids.Both adipocyte-and ADSC-derived EVs regulate local inflammatory levels,tumor progression,and insulin sensitivity.These two types of EVs also have significant therapeutic effects on damage repair,including wound healing,angiogenesis,myocardial damage,vessel re-endothelialization,bone and cartilage regeneration,muscle repair,and nerve repair.With regard to wound healing,microRNA-21,microRNA-126,microRNA-31,and long non-coding RNA-H19 accelerate the proliferation and migration of fibroblasts,human immortalized keratinocytes,and endothelial cells via the PI3K/Akt/ERK pathway or fibrillin 1.ADSC-derived EVs contain various growth factors that are beneficial for wound healing.Numerous miRNAs in ADSC-derived EVs and β3-adrenergic receptors on brown adipocytes exhibit protective effects against myocardial infarction.Proteins in adipocyte-and ADSC-derived EVs play a role in promoting vessel re-endothelialization and regulating vasodilation.Angiogenesis is beneficial for the regeneration and repair of injured bone,cartilage,muscle,and nerves.Compared with adipocyte EVs,ADSC-EVs contain a greater variety of miRNAs and proteins that promote tissue regeneration.EV therapy is a promising cell-free therapy,and EV-loaded materials have been used for wound healing and myocardial damage.Future research will focus on identifying the molecules in EVs and the repair mechanisms that contribute to damage repair and regeneration.In addition,we aim to discover materials designed for slow release and specificity to facilitate tissue repair and optimize EV transportation.展开更多
BACKGROUND Radiation resistance limits radiotherapy efficacy in esophageal squamous cell carcinoma(ESCC).The tumor microenvironment,particularly adipocytes,plays a role in promoting cancer progression.Extracellular ve...BACKGROUND Radiation resistance limits radiotherapy efficacy in esophageal squamous cell carcinoma(ESCC).The tumor microenvironment,particularly adipocytes,plays a role in promoting cancer progression.Extracellular vesicles and microRNAs(miRNAs)regulate gene expression and hold prognostic potential for esophageal carcinoma.Elucidating radioresistance mechanisms and identifying radiosensitization targets can help enhance radiotherapy efficacy for esophageal cancer.AIM To investigate the potential role of miRNAs derived from adipocyte exosomes as prognostic markers for radiotherapy efficacy in ESCC.METHODS Free adipocytes were isolated from human thoracic adipose tissue.A co-culture model of adipocytes and ESCC cells was established to observe colony formation and cell survival post-irradiation.ESCC cell apoptosis was assessed by flow cytometry.Western Blot and immunofluorescence assays were performed to evaluate DNA damage in ESCC cells post-irradiation.Adipocyte-derived exosomes were isolated by ultracentrifugation and identified by electron microscopy.A similar set of experiments was performed on ESCC cells to analyze cell survival,apoptosis,and DNA damage post-radiation exposure.Exosomes from adipose tissue and serum exosomes from ESCC patients pre-and post-radiotherapy were subjected to high-throughput miRNA-sequencing and validated using real-time quantitative polymerase chain reaction.The correlation between potential target miRNAs and the short-term prognosis of radiotherapy in ESCC was evaluated by receiver operating characteristic curve analysis.RESULTS Co-culturing adipocytes with ESCC cells enhanced radioresistance,as evidenced by increased colony formation.Adipocyte co-culture reduced ESCC cell apoptosis and DNA damage post-radiation.Adipocyte-derived exosomes similarly conferred radioresistance in ESCC cells,decreasing apoptosis and DNA damage post-irradiation.Highthroughput miRNA-sequencing identified miR-660-5p in serum and adipose tissue exosomes.Patients with high expression of serum exosome miR-660-5p showed poor prognosis after radiotherapy.CONCLUSION Adipocyte-derived exosomal miR-660-5p is a potential biomarker for evaluating radiotherapy efficacy in ESCC.展开更多
BACKGROUND Adipocytes,especially adipocytes within tumor tissue known as cancer-associated adipocytes,have been increasingly recognized for their pivotal role in the tumor microenvironment of gastric cancer(GC).Their ...BACKGROUND Adipocytes,especially adipocytes within tumor tissue known as cancer-associated adipocytes,have been increasingly recognized for their pivotal role in the tumor microenvironment of gastric cancer(GC).Their influence on tumor progression and patient prognosis has sparked significant interest in recent research.The main objectives of this study were to investigate adipocyte infiltration,assess its correlation with clinical pathological features,develop a prognostic prediction model based on independent prognostic factors,evaluate the impact of adipocytes on immune cell infiltration and tumor invasiveness in GC,and identify and validate genes associated with high adipocyte expression,exploring their potential diagnostic and prognostic value.AIM To explore the relationship between increased adipocytes within tumor tissue and prognosis in GC patients as well as the associated mechanisms and potential biomarkers,using public databases and clinical data.METHODS Using mRNA microarray datasets from the Gene Expression Omnibus database and clinical samples from Jiangsu Provincial Hospital,survival and regression analyses were conducted to determine the relevant prognostic factors in GC.Feature gene selection was performed using least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms,followed by differential gene expression analysis,gene ontology,pathway analysis,and Gene Set Enrichment Analysis.Immune cell infiltration was analyzed using the CIBERSORT algorithm.RESULTS Tumor adipocyte infiltration correlated with poor prognosis in GC,leading to the development of a highly accurate and discriminative prognostic prediction model.Key genes,ADH1B,SFRP1,PLAC9,and FABP4,were identified as associated with high adipocyte expression in GC.The diagnostic and prognostic potential of these identified genes was validated using independent datasets.Downregulation of immune cells was observed in GC with high adipocyte expression.CONCLUSION GC with high intratumoral adipocyte expression demonstrated aggressive tumor biology and a poorer prognosis.The genes ADH1B,SFRP1,PLAC9,and FABP4 have been identified as holding diagnostic and prognostic significance in GC.These findings strongly support the use of adipocyte expression as a valuable indicator of tumor invasiveness and anticipated patient outcomes in GC.展开更多
Background Pork quality is affected by the type of muscle fibers, which is closely related to meat color, tenderness and juiciness. Exosomes are tiny vesicles with a diameter of approximately 30–150 nm that are secre...Background Pork quality is affected by the type of muscle fibers, which is closely related to meat color, tenderness and juiciness. Exosomes are tiny vesicles with a diameter of approximately 30–150 nm that are secreted by cells and taken up by recipient cells to mediate communication. Exosome-mediated muscle-fat tissue crosstalk is a newly discovered mechanism that may have an important effect on intramuscular fat deposition and with that on meat quality. Various of adipose tissue-derived exosomes have been discovered and identified, but the identification and function of muscle exosomes, especially porcine fast/slow myotube exosomes, remain unclear. Here, we first isolated and identified exosomes secreted from porcine extensor digitorum longus(EDL) and soleus(SOL), which represent fast and slow muscle, respectively, and further explored their effects on lipid accumulation in longissimus dorsi adipocytes.Results Porcine SOL-derived exosomes(SOL-EXO) and EDL-derived exosomes(EDL-EXO) were first identified and their average particle sizes were approximately 84 nm with double-membrane disc-shapes as observed via transmission electron microscopy and scanning electron microscopy. Moreover, the intramuscular fat content of the SOL was greater than that of the EDL at 180 days of age, because SOL intramuscular adipocytes had a stronger lipid-accumulating capacity than those of the EDL. Raman spectral analysis revealed that SOL-EXO protein content was much greater than that of EDL-EXO. Proteomic sequencing identified 72 proteins that were significantly differentially expressed between SOL-EXO and EDL-EXO, 31 of which were downregulated and 41 of which were upregulated in SOL-EXO.Conclusions Our findings suggest that muscle-fat tissue interactions occur partly via SOL-EXO promoting adipogenic activity of intramuscular adipocytes.展开更多
Probiotics crosstalk immunity to improve host glycolipid metabolism,which is a new strategy for obesity.This study aimed to explore the functions of Lacticaseibacillus paracasei K56(K56),in regulating the lipid metabo...Probiotics crosstalk immunity to improve host glycolipid metabolism,which is a new strategy for obesity.This study aimed to explore the functions of Lacticaseibacillus paracasei K56(K56),in regulating the lipid metabolism of adipocytes and its immune regulation mechanisms.We co-cultured RAW264.7 macrophages with K56,and the K56-stimulated RAW264.7-conditioned medium(K56-CM)was collected and treated with 3T3-L1 pre-adipocytes.The expression of lipid metabolism-related markers of adipocytes,and the content of cytokines in CMs were detected.The results demonstrated that K56-CM promoted the expression of peroxisome proliferator-activated receptor-γ(PPAR-γ),CCAAT/enhancer binding proteinα(C/EBPα),and other adipogenesis-related markers,which resulted in the upregulation of lipolysis markers,such as hormone-sensitive lipase(HSL),adipose triglyceride lipase(ATGL).The activation of lipolysis enhanced the expression of fatty acidβ-oxidation-related and mitochondrial biogenesis-related markers and reduced lipid accumulation in adipocytes.The glycolipid metabolism pattern of K56 may be due to its immunomodulatory characteristics,which stimulated macrophages to secrete fewer TNF-α,thereby promoting the expression of lipolysis-related markers,and TNF-αsynergized with lipase to promote lipolysis.It has not been reported that L.paracasei modulated lipid metabolism via the lipolysis pathway,which suggested that K56 may regulate glycolipid metabolism of the host by maintaining immune homeostasis.展开更多
Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on ...Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes.Results Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages(d 90 of gestation, G90;d 0 after lactation, L0;d 20 after lactation, L20;2 d post natural involution, PI2;7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation(G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation(L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution(PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells to maintain the lactation potential of mammary glands for the next lactation cycle.Conclusion The molecular mechanisms of dedifferentiation, proliferation and redifferentiation of adipocytes and epithelial cells were revealed from late pregnancy to natural involution. This cell transcriptomic profile constitutes an essential reference for future studies in the development and remodeling of the mammary gland at different stages.展开更多
Colorectal cancer(CRC)is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells.It is increasingly recognized that tumour progression is also regulated by tu...Colorectal cancer(CRC)is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells.It is increasingly recognized that tumour progression is also regulated by tumour microenvironment(TME).The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis.Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors(angiogenic/inflammatory/immune)which contribute to cancer cell proliferation,invasion,neoangiogenesis,evasion of immune surveillance and therapy resistance.Furthermore,adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells.Interestingly,a relationship between obesity and molecular variants in CRC has recently been identified.Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored.This editorial highlights the major findings related to crosstalk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression.Furthermore,we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells.This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression.展开更多
6a-Hydroxylup-20(29)-en-3-on-28-oic acid(1),a natural triterpenoid,was found to possess the ability in a dose-dependent manner inhibiting hormone-induced adipocyte differentiation in 3T3-L1 preadipocytes,and restoring...6a-Hydroxylup-20(29)-en-3-on-28-oic acid(1),a natural triterpenoid,was found to possess the ability in a dose-dependent manner inhibiting hormone-induced adipocyte differentiation in 3T3-L1 preadipocytes,and restoring glucose consuming ability in dexamethasone(DXM)-induced insulin resistant 3T3-L1 adipocytes.Compound 1 was also found to ameliorate DXM-induced adipocyte dysfunction in lipolysis and adipokine secretion.Mechanistic studies revealed that 1 inhibited adipocyte differentiation in 3T3-L1 preadipocytes via down-regulating hormone-stimulated gene transcription of peroxisome proliferator-activated receptor c and CCAAT-enhancer-binding protein alpha which are key factors in lipogenesis,and restored DXM-impaired glucose consuming ability in differentiated 3T3-L1 adipocytes via repairing insulin signaling pathway and activating down-stream signaling transduction by phosphorylation of signaling molecules PI3K/p85,Akt2 and AS160,thus leading to increased translocation of glucose transporter type 4 and transportation of glucose.展开更多
Conjugated linoleic acids （CLAs） are a generic term for linoleic acid isomers and have a variety of biological functions. After rat preadi- pocytes were incubated in CLAs-supplemented media, their proliferation and ...Conjugated linoleic acids （CLAs） are a generic term for linoleic acid isomers and have a variety of biological functions. After rat preadi- pocytes were incubated in CLAs-supplemented media, their proliferation and differentiation were observed by the cell count and the oil red O stai- ning. The results showed that the CLAs at different concentrations inhibited proliferation of the rat preadipocytes in a time- and dose-dependent manner. And the CLAs greatly decreased intracellular lipid content in mature adipocytes. Moreover, lipogenesis was inhibited by the CLAs in a dose-dependent manner. Therefore, the CLAs inhibit the lipogenesis by reducing the number of preadipocytes and decreasing the intracellular lipid展开更多
Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus（T2DM）, and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as dr...Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus（T2DM）, and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as drug candidates for diabetes based on their insulin-like action. However, few studies focus on their antilipolytic effect. In the present study, we established an insulin-resistant model in 3T3-L1 adipocytes to mimic pathological conditions of T2DM according to a well-established method by the treatment of high concentrations of glucose and insulin, which was validated by oil red O staining and the decreased levels of phosphorylated Akt, AS160 and GSK3 after insulin treatment. The results demonstrated that bis（acetylacetonato）-oxidovanadium（Ⅳ）（VO（acac）_2） could inhibit isoproterenol-stimulated lipolysis through the reduction of the phosphorylated HSL and perilipin levels in both insulin-sensitive and insulin-resistant 3T3-L1 adipocytes. Moreover, although the levels of phosphorylated Akt induced by VO（acac）_2 were decreased, the rates of lipolytic inhibition were not significantly altered compared with those under insulin-sensitive condition, indicating that the anti-lipolytic effect of VO（acac）_2 might also function in an Akt-independent way in insulin-resistant adipocytes. Our work here help elucidate the anti-diabetic effects of vanadium compounds. It may not only shed light on the utility of vanadium-based compounds as potential anti-diabetic drugs but also serve as a useful screening model for new anti-diabetic drugs.展开更多
Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, mo...Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis. Recently, brownlike adipocytes were discovered in WAT. These brownlike adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expressionpattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation(adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.展开更多
Objective To investigate the attenuating effect of curcumin, an anti-inflammatory compound derived from dietary spice turmeric （Curcuma longa） on the pro-inflammatory insulin-resistant state in 3T3-L1 adipocytes. Me...Objective To investigate the attenuating effect of curcumin, an anti-inflammatory compound derived from dietary spice turmeric （Curcuma longa） on the pro-inflammatory insulin-resistant state in 3T3-L1 adipocytes. Methods Glucose uptake rate was determined with the [3H] 2-deoxyglucose uptake method. Expressions of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were measured by quantitative RT-PCR analysis and ELISA. Nuclear transcription factor kappaB p65 （NF-r,B p65） and mitogen-activated protein kinase （MAPKs） were detected by Western blot assay. Results The basal glucose uptake was not altered, and curcumin increased the insulin-stimulated glucose uptake in 3T3-L1 cells. Curcumin suppressed the transcription and secretion of TNF-α and IL-6 induced by palmitate in a concentration-dependent manner. Palmitate induced nuclear translocation of NF-kB. The activities of Jun NH2-terminal kinase ONK）, extracellular signal-regulated kinasel/2 （ERKI/2） and p38MAPK decreased in the presence of curcumin. Moreover, pretreatment with SP600125 （inhibitor of JNK） instead of PD98059 or SB203580 （inhibitor of ERKI/2 or p38MAPK, respectively） decreased the up-regulation of TNF-α induced by palmitate. Conelusion Curcumin reverses palmitate-induced insulin resistance state in 3T3-L1 adipocytes through the NF-kB and JNK pathway.展开更多
AIM： To detect plasma levels of new adipocyte derived hormone adiponectin and resistin in type 2 diabetes patients and to explore their potential roles in insulin resistance in type 2 diabetes. METHODS： According to...AIM： To detect plasma levels of new adipocyte derived hormone adiponectin and resistin in type 2 diabetes patients and to explore their potential roles in insulin resistance in type 2 diabetes. METHODS： According to the body mass index （BMI）, 60 type 2 diabetes patients were divided into two groups, one group was non-obese diabetes patients with BMI 〈 25Kg/M^2 （30 cases） and the other group was obese diabetes patients with BMI 〉25Kg/M^2 （30 cases）. There were 28 healthy persons in the control group. EUSA technique was employed to determine the plasma adiponectin and resistin concentrations. The fasting blood glucose, insulin and blood lipid were detected respectively by electrocheminescence immunoassay and immunoturbidimetric assay. Insulin resistance index and insulin sensitive index were calculated by the homeostasis model assessment （HOMO）. RESULTS： The levels of plasma adiponectin were decreased significantly in diabetes group compared to that in control group （non-obese： 8.58±0.86, obese： 6.22±1.34 vs 10.53±1.47 P〈0.05）; moreover, adiponectin concentration in obese diabetes group was significantly decreased compared to that in non-obese diabetes group （6.22±1.34 vs 8.58±0.86, P〈 0.05）. The levels of plasma resistin were increased significantly in diabetes group compared to that in control group （obese： 18.64 ± 4.65, non-obese： 24.05±9.07 vs 14.16±5.25, P〈0.05,P〈0.05）; furthermore, the levels of resistin in obese diabetes group were increased significantly compared to that in non-obese diabetes group （P〈 0.05）. Plasma adiponectin was correlated negatively with BMI, blood glucose, insulin resistance index and triglyceride （respectively, r=-0.55, P〈0.01; r=-0.51, P〈0.05; r=-0.52, P〈 0.05： r=-0.39, P〈 0.05）, while it was positively correlated with insulin sensitive index （r=0.45, P〈0.05）. Conversely, plasma resistin correlated positively with BMI, blood glucose, triglyceride and insulin resistance index （respectively, r=0.40, P〈 0.05; r= 0.52, P〈0.05; r= 0.46, P〈 0.01; r= 0.27, P〈 0.05）, and negatively correlated with insulin sensitive index （r=-0.32, P〈 0.05）. CONCLUSION： Plasma adiponectin and resistin are associatecl with the disorder of metabolism of glucose and lipid in diabetes. The relationship between these hormone and insulin sensitivity suggests that they may take part in the development of insulin resistance of type 2 diabetes.展开更多
Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free...Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free system.Then,interleukin-1βand interferon-γinduced cell death and insulin secretion were measured in rat insulinoma(RIN)cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA kit,respectively.Glucose uptake and glucose transporter expression were measured by fluorometry and western blotting,using 3T3-Ll adipocytes.Results:C.lentillifera extract significantly decreased dipeptidyl peptidase-IV and a-glucosidase enzyme activities,and effectively inhibited cell death and iNOS expression in interleukin-1βand interfcron-γinduced RIK cells.Furthermore,C.lntillifera extract significantly enhanced insulin secretion in RTN cells and glucose transporter expression and glucose uptake in 3T3-L1adipocytes.Conclusions:Thus,our results suggest that C.lentillifera could be used as a potential antidiabetic agenl.展开更多
In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and gluc...In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and glucose metabolism using differentiated 3T3L1 adipocytes as a model system. By confocal laser scanning microscopy, we found that VO（acac）2 induced ROS generation under high glucose stimulation, and the pretreatment of NADPH oxidase inhibitors could significantly reduce the elevated ROS level. Meanwhile, the decreased phosphorylated levels of AKT and the two key modulators of lipolysis（HSL and perilipin） were observed by western blot analysis. We also found that the contents of glycerol release were further reduced as well. In addition, the levels of key regulatory proteins, AS160 and GSK3β, in glucose metabolism pathway were correspondingly reduced. These findings demonstrated that ROS induced by vanadium compounds could act as a metabolic signal to activate AKT pathway to inhibit lipolysis and promote glucose transport and glycogen synthesis rather than by direct action by themselves. Our study contributed to elucidate the anti-diabetic effects of vanadium compounds and provided a theoretical basis for the further development of new vanadium complexes in the prevention and therapeutics of diabetes.展开更多
Age-related osteoporosis is associated with the reduced capacity of bone marrow mesenchymal stem cells （BMSCs） to differentiate into osteoblasts instead of adipocytes. However, the molecular mechanisms that decide t...Age-related osteoporosis is associated with the reduced capacity of bone marrow mesenchymal stem cells （BMSCs） to differentiate into osteoblasts instead of adipocytes. However, the molecular mechanisms that decide the fate of BMSCs remain unclear. In our study, microRNA-23a, and microRNA-23b （miR-23a/b） were found to be markedly downregulated in BMSCs of aged mice and humans. The overexpression of miR-23a/b in BMSCs promoted osteogenic differentiation, whereas the inhibition of miR-23a/b increased adipogenic differentiation. Transmembrane protein 64 （Tmem64）, which has expression levels inversely related to those of miR-23a/b in aged and young mice, was identified as a major target of miR-23a/b during BMSC differentiation. In conclusion, our study suggests that miR-23a/b has a critical role in the regulation of mesenchymal lineage differentiation through the suppression of Tmem64.展开更多
Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem ce...Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells(BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2(Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling.RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging.展开更多
Objective:Obesity is closely associated with metastasis in breast cancer patients.Secreted frizzled-related protein 5(SFRP5),one of the novel adipokines with anti-inflammatory properties,is associated with obesity.Thi...Objective:Obesity is closely associated with metastasis in breast cancer patients.Secreted frizzled-related protein 5(SFRP5),one of the novel adipokines with anti-inflammatory properties,is associated with obesity.This study aims to study the role of SFRP5 in the crosstalk between obesity and breast cancer metastasis and identify the underlying mechanism.Methods:3T3-L1 pre-adipocytes were differentiated to mature adipocytes and a hypertrophic adipocyte model was induced with palmitic acid(PA).Cell motility was measured in MDA-MB-231 and MCF-7 breast cancer cells co-cultured with adipocytes conditioned medium(CM)with or without SFRP5 protein.Wnt and epithelialmesenchymal transition(EMT)signal pathways were investigated by western blot.Circulating SFRP5 level in 218 breast cancer patients and the association with clinicopathologic characteristics of breast cancer were further determined.Online databases ENCORI and PREDICT Plus were used to exam the link between SFRP5 and prognosis.Results:Reduced SFRP5 level was detected in the hypertrophic adipocyte model.Recombinant SFRP5 protein inhibited MDA-MB-231 and MCF-7 cells invasion and migration induced by PA-treated adipocyte CM,and SFRP5 inhibition by specific antibody reversed the effect of SFRP5.Furthermore,SFRP5 significantly inhibited Wnt and downstream EMT in breast cancer cells.Low circulating SFRP5 level correlated with body mass index(BMI),lymph node(LN)metastasis,TNM stage and high Ki67 expression in breast cancer patients.Increased SFRP5 level was associated with favorable predicted survival.Kaplan-Meier curves showed high SFRP5 level in tumor tissue was associated with better outcome of breast cancer patients.Conclusions:Our findings demonstrated SFRP5 is a vital adipokine that mediates the crosslink between obesity and the metastatic potential of breast cancer.Promotion of SFRP5 expression in the adipose microenvironment may represent a novel approach for preventing breast cancer metastasis.展开更多
Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic s...Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.展开更多
We investigated the ability of fetal mesenchymal stem cells （fMSCs） to differentiate into brown and white adi- pocytes and compared the expression of a number of marker genes and key regulatory factors. We showed th...We investigated the ability of fetal mesenchymal stem cells （fMSCs） to differentiate into brown and white adi- pocytes and compared the expression of a number of marker genes and key regulatory factors. We showed that the expression of key adipocyte regulators and markers during differentiation is similar to that in other human and mu- rine adipocyte models, including induction of PPARy2 and FABP4. Notably, we found that the preadipocyte marker, Pref-1, is induced early in differentiation and then declines markedly as the process continues, suggesting that fMSCs first acquire preadipocyte characteristics as they commit to the adipogenic lineage, prior to their differentiation into mature adipocytes. After adipogenic induction, some stem cell isolates differentiated into cells resembling brown adi- pocytes and others into white adipocytes. Detailed investigation of one isolate showed that the novel brown fat-deter- mining factor PRDM16 is expressed both before and after differentiation. Importantly, these cells exhibited elevated basal UCP-1 expression, which was dependent on the activity of the orphan nuclear receptor ERRa, highlighting a novel role for ERRa in human brown fat. Thus fMSCs represent a useful in vitro model for human adipogenesis, and provide opportunities to study the stages prior to commitment to the adipocyte lineage. They also offer invaluable in- sights into the characteristics of human brown fat.展开更多
基金supported by the National Natural Science Foundation of China(grant no.82272287).
文摘Adipocyte-secreted extracellular vesicles(EVs)and adipose-derived stem cells(ADSCs)regulate physiological and pathological processes by delivering nucleic acids,proteins,and lipids.Both adipocyte-and ADSC-derived EVs regulate local inflammatory levels,tumor progression,and insulin sensitivity.These two types of EVs also have significant therapeutic effects on damage repair,including wound healing,angiogenesis,myocardial damage,vessel re-endothelialization,bone and cartilage regeneration,muscle repair,and nerve repair.With regard to wound healing,microRNA-21,microRNA-126,microRNA-31,and long non-coding RNA-H19 accelerate the proliferation and migration of fibroblasts,human immortalized keratinocytes,and endothelial cells via the PI3K/Akt/ERK pathway or fibrillin 1.ADSC-derived EVs contain various growth factors that are beneficial for wound healing.Numerous miRNAs in ADSC-derived EVs and β3-adrenergic receptors on brown adipocytes exhibit protective effects against myocardial infarction.Proteins in adipocyte-and ADSC-derived EVs play a role in promoting vessel re-endothelialization and regulating vasodilation.Angiogenesis is beneficial for the regeneration and repair of injured bone,cartilage,muscle,and nerves.Compared with adipocyte EVs,ADSC-EVs contain a greater variety of miRNAs and proteins that promote tissue regeneration.EV therapy is a promising cell-free therapy,and EV-loaded materials have been used for wound healing and myocardial damage.Future research will focus on identifying the molecules in EVs and the repair mechanisms that contribute to damage repair and regeneration.In addition,we aim to discover materials designed for slow release and specificity to facilitate tissue repair and optimize EV transportation.
基金Supported by the National Natural Science Foundation of China,No.81602792 and No.12205215and Science and Technology Program of Nantong,No.JC12022103.
文摘BACKGROUND Radiation resistance limits radiotherapy efficacy in esophageal squamous cell carcinoma(ESCC).The tumor microenvironment,particularly adipocytes,plays a role in promoting cancer progression.Extracellular vesicles and microRNAs(miRNAs)regulate gene expression and hold prognostic potential for esophageal carcinoma.Elucidating radioresistance mechanisms and identifying radiosensitization targets can help enhance radiotherapy efficacy for esophageal cancer.AIM To investigate the potential role of miRNAs derived from adipocyte exosomes as prognostic markers for radiotherapy efficacy in ESCC.METHODS Free adipocytes were isolated from human thoracic adipose tissue.A co-culture model of adipocytes and ESCC cells was established to observe colony formation and cell survival post-irradiation.ESCC cell apoptosis was assessed by flow cytometry.Western Blot and immunofluorescence assays were performed to evaluate DNA damage in ESCC cells post-irradiation.Adipocyte-derived exosomes were isolated by ultracentrifugation and identified by electron microscopy.A similar set of experiments was performed on ESCC cells to analyze cell survival,apoptosis,and DNA damage post-radiation exposure.Exosomes from adipose tissue and serum exosomes from ESCC patients pre-and post-radiotherapy were subjected to high-throughput miRNA-sequencing and validated using real-time quantitative polymerase chain reaction.The correlation between potential target miRNAs and the short-term prognosis of radiotherapy in ESCC was evaluated by receiver operating characteristic curve analysis.RESULTS Co-culturing adipocytes with ESCC cells enhanced radioresistance,as evidenced by increased colony formation.Adipocyte co-culture reduced ESCC cell apoptosis and DNA damage post-radiation.Adipocyte-derived exosomes similarly conferred radioresistance in ESCC cells,decreasing apoptosis and DNA damage post-irradiation.Highthroughput miRNA-sequencing identified miR-660-5p in serum and adipose tissue exosomes.Patients with high expression of serum exosome miR-660-5p showed poor prognosis after radiotherapy.CONCLUSION Adipocyte-derived exosomal miR-660-5p is a potential biomarker for evaluating radiotherapy efficacy in ESCC.
基金Supported by National Traditional Chinese Medicine Inheritance and Innovation Platform Construction Project by National Administration of Traditional Chinese Medicine,No.Y2020CX57Jiangsu Provincial Administration of Traditional Chinese Medicine,No.MS2023014Jiangsu Graduate Student Research and Practice Innovation Program,No.SJCX23_0799。
文摘BACKGROUND Adipocytes,especially adipocytes within tumor tissue known as cancer-associated adipocytes,have been increasingly recognized for their pivotal role in the tumor microenvironment of gastric cancer(GC).Their influence on tumor progression and patient prognosis has sparked significant interest in recent research.The main objectives of this study were to investigate adipocyte infiltration,assess its correlation with clinical pathological features,develop a prognostic prediction model based on independent prognostic factors,evaluate the impact of adipocytes on immune cell infiltration and tumor invasiveness in GC,and identify and validate genes associated with high adipocyte expression,exploring their potential diagnostic and prognostic value.AIM To explore the relationship between increased adipocytes within tumor tissue and prognosis in GC patients as well as the associated mechanisms and potential biomarkers,using public databases and clinical data.METHODS Using mRNA microarray datasets from the Gene Expression Omnibus database and clinical samples from Jiangsu Provincial Hospital,survival and regression analyses were conducted to determine the relevant prognostic factors in GC.Feature gene selection was performed using least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms,followed by differential gene expression analysis,gene ontology,pathway analysis,and Gene Set Enrichment Analysis.Immune cell infiltration was analyzed using the CIBERSORT algorithm.RESULTS Tumor adipocyte infiltration correlated with poor prognosis in GC,leading to the development of a highly accurate and discriminative prognostic prediction model.Key genes,ADH1B,SFRP1,PLAC9,and FABP4,were identified as associated with high adipocyte expression in GC.The diagnostic and prognostic potential of these identified genes was validated using independent datasets.Downregulation of immune cells was observed in GC with high adipocyte expression.CONCLUSION GC with high intratumoral adipocyte expression demonstrated aggressive tumor biology and a poorer prognosis.The genes ADH1B,SFRP1,PLAC9,and FABP4 have been identified as holding diagnostic and prognostic significance in GC.These findings strongly support the use of adipocyte expression as a valuable indicator of tumor invasiveness and anticipated patient outcomes in GC.
基金supported by the National Natural Science Foundation of China (32272847, U22A20516)the Key Research and Development Program of Shaanxi Province (2022ZDLNY01-04)the China Agriculture Research System of MOF and MARA (CARS-35)。
文摘Background Pork quality is affected by the type of muscle fibers, which is closely related to meat color, tenderness and juiciness. Exosomes are tiny vesicles with a diameter of approximately 30–150 nm that are secreted by cells and taken up by recipient cells to mediate communication. Exosome-mediated muscle-fat tissue crosstalk is a newly discovered mechanism that may have an important effect on intramuscular fat deposition and with that on meat quality. Various of adipose tissue-derived exosomes have been discovered and identified, but the identification and function of muscle exosomes, especially porcine fast/slow myotube exosomes, remain unclear. Here, we first isolated and identified exosomes secreted from porcine extensor digitorum longus(EDL) and soleus(SOL), which represent fast and slow muscle, respectively, and further explored their effects on lipid accumulation in longissimus dorsi adipocytes.Results Porcine SOL-derived exosomes(SOL-EXO) and EDL-derived exosomes(EDL-EXO) were first identified and their average particle sizes were approximately 84 nm with double-membrane disc-shapes as observed via transmission electron microscopy and scanning electron microscopy. Moreover, the intramuscular fat content of the SOL was greater than that of the EDL at 180 days of age, because SOL intramuscular adipocytes had a stronger lipid-accumulating capacity than those of the EDL. Raman spectral analysis revealed that SOL-EXO protein content was much greater than that of EDL-EXO. Proteomic sequencing identified 72 proteins that were significantly differentially expressed between SOL-EXO and EDL-EXO, 31 of which were downregulated and 41 of which were upregulated in SOL-EXO.Conclusions Our findings suggest that muscle-fat tissue interactions occur partly via SOL-EXO promoting adipogenic activity of intramuscular adipocytes.
基金supported by the Yili Industrial Group Co., Ltd., and National Natural Science Foundation of China (81973042).
文摘Probiotics crosstalk immunity to improve host glycolipid metabolism,which is a new strategy for obesity.This study aimed to explore the functions of Lacticaseibacillus paracasei K56(K56),in regulating the lipid metabolism of adipocytes and its immune regulation mechanisms.We co-cultured RAW264.7 macrophages with K56,and the K56-stimulated RAW264.7-conditioned medium(K56-CM)was collected and treated with 3T3-L1 pre-adipocytes.The expression of lipid metabolism-related markers of adipocytes,and the content of cytokines in CMs were detected.The results demonstrated that K56-CM promoted the expression of peroxisome proliferator-activated receptor-γ(PPAR-γ),CCAAT/enhancer binding proteinα(C/EBPα),and other adipogenesis-related markers,which resulted in the upregulation of lipolysis markers,such as hormone-sensitive lipase(HSL),adipose triglyceride lipase(ATGL).The activation of lipolysis enhanced the expression of fatty acidβ-oxidation-related and mitochondrial biogenesis-related markers and reduced lipid accumulation in adipocytes.The glycolipid metabolism pattern of K56 may be due to its immunomodulatory characteristics,which stimulated macrophages to secrete fewer TNF-α,thereby promoting the expression of lipolysis-related markers,and TNF-αsynergized with lipase to promote lipolysis.It has not been reported that L.paracasei modulated lipid metabolism via the lipolysis pathway,which suggested that K56 may regulate glycolipid metabolism of the host by maintaining immune homeostasis.
基金supported by the National Key R&D Program of China (2020YFA0509500,2021YFD1301101 and 2021YFA0805903)the Sichuan Science and Technology Program+3 种基金(2023YFN0088 and 2021YFYZ0030)the National Center of Technology Innovation for Pigs (SCCXTD-2023-08)the National Natural Science Foundation of China (32272837 and 32225046)Tianfu Agricultural Master Project。
文摘Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes.Results Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages(d 90 of gestation, G90;d 0 after lactation, L0;d 20 after lactation, L20;2 d post natural involution, PI2;7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation(G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation(L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution(PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells to maintain the lactation potential of mammary glands for the next lactation cycle.Conclusion The molecular mechanisms of dedifferentiation, proliferation and redifferentiation of adipocytes and epithelial cells were revealed from late pregnancy to natural involution. This cell transcriptomic profile constitutes an essential reference for future studies in the development and remodeling of the mammary gland at different stages.
文摘Colorectal cancer(CRC)is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells.It is increasingly recognized that tumour progression is also regulated by tumour microenvironment(TME).The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis.Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors(angiogenic/inflammatory/immune)which contribute to cancer cell proliferation,invasion,neoangiogenesis,evasion of immune surveillance and therapy resistance.Furthermore,adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells.Interestingly,a relationship between obesity and molecular variants in CRC has recently been identified.Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored.This editorial highlights the major findings related to crosstalk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression.Furthermore,we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells.This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression.
基金China National Major Projects of Science&Technology(2014ZX100050022009ZX09103-436)+1 种基金the Young Academic Leader Raising Foundation of Yunnan Province(No.2009CI073)the foundation from Chinese Academy of Sciences to Gang Xu,and the Program for Research Team in South China Chinese Medicine Collaborative Innovation Center of Guangdong,China(A1-AFD01514A07).
文摘6a-Hydroxylup-20(29)-en-3-on-28-oic acid(1),a natural triterpenoid,was found to possess the ability in a dose-dependent manner inhibiting hormone-induced adipocyte differentiation in 3T3-L1 preadipocytes,and restoring glucose consuming ability in dexamethasone(DXM)-induced insulin resistant 3T3-L1 adipocytes.Compound 1 was also found to ameliorate DXM-induced adipocyte dysfunction in lipolysis and adipokine secretion.Mechanistic studies revealed that 1 inhibited adipocyte differentiation in 3T3-L1 preadipocytes via down-regulating hormone-stimulated gene transcription of peroxisome proliferator-activated receptor c and CCAAT-enhancer-binding protein alpha which are key factors in lipogenesis,and restored DXM-impaired glucose consuming ability in differentiated 3T3-L1 adipocytes via repairing insulin signaling pathway and activating down-stream signaling transduction by phosphorylation of signaling molecules PI3K/p85,Akt2 and AS160,thus leading to increased translocation of glucose transporter type 4 and transportation of glucose.
基金funded by Scientific and Technological Research Project of Chongqing Municipal Education Commission (KJ080827)National Natural Science Foundation of China (30800843)the Key Disciplines of Zoology of chongqing, chongqing Normal University
文摘Conjugated linoleic acids （CLAs） are a generic term for linoleic acid isomers and have a variety of biological functions. After rat preadi- pocytes were incubated in CLAs-supplemented media, their proliferation and differentiation were observed by the cell count and the oil red O stai- ning. The results showed that the CLAs at different concentrations inhibited proliferation of the rat preadipocytes in a time- and dose-dependent manner. And the CLAs greatly decreased intracellular lipid content in mature adipocytes. Moreover, lipogenesis was inhibited by the CLAs in a dose-dependent manner. Therefore, the CLAs inhibit the lipogenesis by reducing the number of preadipocytes and decreasing the intracellular lipid
基金supported by National Natural Science Foundation of China(Grant No.21171011 and 21671009)
文摘Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus（T2DM）, and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as drug candidates for diabetes based on their insulin-like action. However, few studies focus on their antilipolytic effect. In the present study, we established an insulin-resistant model in 3T3-L1 adipocytes to mimic pathological conditions of T2DM according to a well-established method by the treatment of high concentrations of glucose and insulin, which was validated by oil red O staining and the decreased levels of phosphorylated Akt, AS160 and GSK3 after insulin treatment. The results demonstrated that bis（acetylacetonato）-oxidovanadium（Ⅳ）（VO（acac）_2） could inhibit isoproterenol-stimulated lipolysis through the reduction of the phosphorylated HSL and perilipin levels in both insulin-sensitive and insulin-resistant 3T3-L1 adipocytes. Moreover, although the levels of phosphorylated Akt induced by VO（acac）_2 were decreased, the rates of lipolytic inhibition were not significantly altered compared with those under insulin-sensitive condition, indicating that the anti-lipolytic effect of VO（acac）_2 might also function in an Akt-independent way in insulin-resistant adipocytes. Our work here help elucidate the anti-diabetic effects of vanadium compounds. It may not only shed light on the utility of vanadium-based compounds as potential anti-diabetic drugs but also serve as a useful screening model for new anti-diabetic drugs.
基金Supported by Grants from the National Research of Foundation of the South Korea,No.2012M3A9C7050101,No.2011-0030028 and No.2006-2004112
文摘Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis. Recently, brownlike adipocytes were discovered in WAT. These brownlike adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expressionpattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation(adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.
基金supported by the Projects in the National Science & Technology Pillar Program during the Eleventh Five-year Plan Period:Research and Industrialization of Functional Foods in Reducing Blood Lipid,Pressure and Glucose(2006-2010.No.2006BAD27B05).
文摘Objective To investigate the attenuating effect of curcumin, an anti-inflammatory compound derived from dietary spice turmeric （Curcuma longa） on the pro-inflammatory insulin-resistant state in 3T3-L1 adipocytes. Methods Glucose uptake rate was determined with the [3H] 2-deoxyglucose uptake method. Expressions of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were measured by quantitative RT-PCR analysis and ELISA. Nuclear transcription factor kappaB p65 （NF-r,B p65） and mitogen-activated protein kinase （MAPKs） were detected by Western blot assay. Results The basal glucose uptake was not altered, and curcumin increased the insulin-stimulated glucose uptake in 3T3-L1 cells. Curcumin suppressed the transcription and secretion of TNF-α and IL-6 induced by palmitate in a concentration-dependent manner. Palmitate induced nuclear translocation of NF-kB. The activities of Jun NH2-terminal kinase ONK）, extracellular signal-regulated kinasel/2 （ERKI/2） and p38MAPK decreased in the presence of curcumin. Moreover, pretreatment with SP600125 （inhibitor of JNK） instead of PD98059 or SB203580 （inhibitor of ERKI/2 or p38MAPK, respectively） decreased the up-regulation of TNF-α induced by palmitate. Conelusion Curcumin reverses palmitate-induced insulin resistance state in 3T3-L1 adipocytes through the NF-kB and JNK pathway.
基金Supported by the National Natural Science Foundation of China, No. 30170442
文摘AIM： To detect plasma levels of new adipocyte derived hormone adiponectin and resistin in type 2 diabetes patients and to explore their potential roles in insulin resistance in type 2 diabetes. METHODS： According to the body mass index （BMI）, 60 type 2 diabetes patients were divided into two groups, one group was non-obese diabetes patients with BMI 〈 25Kg/M^2 （30 cases） and the other group was obese diabetes patients with BMI 〉25Kg/M^2 （30 cases）. There were 28 healthy persons in the control group. EUSA technique was employed to determine the plasma adiponectin and resistin concentrations. The fasting blood glucose, insulin and blood lipid were detected respectively by electrocheminescence immunoassay and immunoturbidimetric assay. Insulin resistance index and insulin sensitive index were calculated by the homeostasis model assessment （HOMO）. RESULTS： The levels of plasma adiponectin were decreased significantly in diabetes group compared to that in control group （non-obese： 8.58±0.86, obese： 6.22±1.34 vs 10.53±1.47 P〈0.05）; moreover, adiponectin concentration in obese diabetes group was significantly decreased compared to that in non-obese diabetes group （6.22±1.34 vs 8.58±0.86, P〈 0.05）. The levels of plasma resistin were increased significantly in diabetes group compared to that in control group （obese： 18.64 ± 4.65, non-obese： 24.05±9.07 vs 14.16±5.25, P〈0.05,P〈0.05）; furthermore, the levels of resistin in obese diabetes group were increased significantly compared to that in non-obese diabetes group （P〈 0.05）. Plasma adiponectin was correlated negatively with BMI, blood glucose, insulin resistance index and triglyceride （respectively, r=-0.55, P〈0.01; r=-0.51, P〈0.05; r=-0.52, P〈 0.05： r=-0.39, P〈 0.05）, while it was positively correlated with insulin sensitive index （r=0.45, P〈0.05）. Conversely, plasma resistin correlated positively with BMI, blood glucose, triglyceride and insulin resistance index （respectively, r=0.40, P〈 0.05; r= 0.52, P〈0.05; r= 0.46, P〈 0.01; r= 0.27, P〈 0.05）, and negatively correlated with insulin sensitive index （r=-0.32, P〈 0.05）. CONCLUSION： Plasma adiponectin and resistin are associatecl with the disorder of metabolism of glucose and lipid in diabetes. The relationship between these hormone and insulin sensitivity suggests that they may take part in the development of insulin resistance of type 2 diabetes.
基金Supported by the Ministry of Education.Science and Technology (Grant No.2012RTAL2009172)
文摘Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free system.Then,interleukin-1βand interferon-γinduced cell death and insulin secretion were measured in rat insulinoma(RIN)cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA kit,respectively.Glucose uptake and glucose transporter expression were measured by fluorometry and western blotting,using 3T3-Ll adipocytes.Results:C.lentillifera extract significantly decreased dipeptidyl peptidase-IV and a-glucosidase enzyme activities,and effectively inhibited cell death and iNOS expression in interleukin-1βand interfcron-γinduced RIK cells.Furthermore,C.lntillifera extract significantly enhanced insulin secretion in RTN cells and glucose transporter expression and glucose uptake in 3T3-L1adipocytes.Conclusions:Thus,our results suggest that C.lentillifera could be used as a potential antidiabetic agenl.
基金National Natural Science Foundation of China(Grant No.20871008 and 21171011)
文摘In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and glucose metabolism using differentiated 3T3L1 adipocytes as a model system. By confocal laser scanning microscopy, we found that VO（acac）2 induced ROS generation under high glucose stimulation, and the pretreatment of NADPH oxidase inhibitors could significantly reduce the elevated ROS level. Meanwhile, the decreased phosphorylated levels of AKT and the two key modulators of lipolysis（HSL and perilipin） were observed by western blot analysis. We also found that the contents of glycerol release were further reduced as well. In addition, the levels of key regulatory proteins, AS160 and GSK3β, in glucose metabolism pathway were correspondingly reduced. These findings demonstrated that ROS induced by vanadium compounds could act as a metabolic signal to activate AKT pathway to inhibit lipolysis and promote glucose transport and glycogen synthesis rather than by direct action by themselves. Our study contributed to elucidate the anti-diabetic effects of vanadium compounds and provided a theoretical basis for the further development of new vanadium complexes in the prevention and therapeutics of diabetes.
文摘Age-related osteoporosis is associated with the reduced capacity of bone marrow mesenchymal stem cells （BMSCs） to differentiate into osteoblasts instead of adipocytes. However, the molecular mechanisms that decide the fate of BMSCs remain unclear. In our study, microRNA-23a, and microRNA-23b （miR-23a/b） were found to be markedly downregulated in BMSCs of aged mice and humans. The overexpression of miR-23a/b in BMSCs promoted osteogenic differentiation, whereas the inhibition of miR-23a/b increased adipogenic differentiation. Transmembrane protein 64 （Tmem64）, which has expression levels inversely related to those of miR-23a/b in aged and young mice, was identified as a major target of miR-23a/b during BMSC differentiation. In conclusion, our study suggests that miR-23a/b has a critical role in the regulation of mesenchymal lineage differentiation through the suppression of Tmem64.
基金supported by the National Natural Science Foundation of China(NSFC)[81672119 and 81725010 to W.Z.]W Z is a scholar of‘the National Science Fund for Distinguished Young Scholars’(NSFC)[81725010]+4 种基金the Strategic Priority Research Program of the Chinese Academy of Science(XDA16020400 to P.H.)Ministry of Science and Technology of China(2017YFA0102700 to P.H.)National Natural Science Foundation of China(32170804 to PH)P.H.the fellowship of China Postdoctoral Science Foundation(2021TQ0207,2021M702184 to J.S.)the‘Basic research project of Shanghai Sixth People’s Hospital’(ynqn202102 to J.S.)。
文摘Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells(BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2(Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling.RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging.
基金the Major Scientific and Technological Innovation Project of Shandong Province(No.2017CXGC1212)National Natural Science Foundation of China(No.31701258)the National Key Research and Development Program of China(No.2016YFC0901300)。
文摘Objective:Obesity is closely associated with metastasis in breast cancer patients.Secreted frizzled-related protein 5(SFRP5),one of the novel adipokines with anti-inflammatory properties,is associated with obesity.This study aims to study the role of SFRP5 in the crosstalk between obesity and breast cancer metastasis and identify the underlying mechanism.Methods:3T3-L1 pre-adipocytes were differentiated to mature adipocytes and a hypertrophic adipocyte model was induced with palmitic acid(PA).Cell motility was measured in MDA-MB-231 and MCF-7 breast cancer cells co-cultured with adipocytes conditioned medium(CM)with or without SFRP5 protein.Wnt and epithelialmesenchymal transition(EMT)signal pathways were investigated by western blot.Circulating SFRP5 level in 218 breast cancer patients and the association with clinicopathologic characteristics of breast cancer were further determined.Online databases ENCORI and PREDICT Plus were used to exam the link between SFRP5 and prognosis.Results:Reduced SFRP5 level was detected in the hypertrophic adipocyte model.Recombinant SFRP5 protein inhibited MDA-MB-231 and MCF-7 cells invasion and migration induced by PA-treated adipocyte CM,and SFRP5 inhibition by specific antibody reversed the effect of SFRP5.Furthermore,SFRP5 significantly inhibited Wnt and downstream EMT in breast cancer cells.Low circulating SFRP5 level correlated with body mass index(BMI),lymph node(LN)metastasis,TNM stage and high Ki67 expression in breast cancer patients.Increased SFRP5 level was associated with favorable predicted survival.Kaplan-Meier curves showed high SFRP5 level in tumor tissue was associated with better outcome of breast cancer patients.Conclusions:Our findings demonstrated SFRP5 is a vital adipokine that mediates the crosslink between obesity and the metastatic potential of breast cancer.Promotion of SFRP5 expression in the adipose microenvironment may represent a novel approach for preventing breast cancer metastasis.
文摘Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.
文摘We investigated the ability of fetal mesenchymal stem cells （fMSCs） to differentiate into brown and white adi- pocytes and compared the expression of a number of marker genes and key regulatory factors. We showed that the expression of key adipocyte regulators and markers during differentiation is similar to that in other human and mu- rine adipocyte models, including induction of PPARy2 and FABP4. Notably, we found that the preadipocyte marker, Pref-1, is induced early in differentiation and then declines markedly as the process continues, suggesting that fMSCs first acquire preadipocyte characteristics as they commit to the adipogenic lineage, prior to their differentiation into mature adipocytes. After adipogenic induction, some stem cell isolates differentiated into cells resembling brown adi- pocytes and others into white adipocytes. Detailed investigation of one isolate showed that the novel brown fat-deter- mining factor PRDM16 is expressed both before and after differentiation. Importantly, these cells exhibited elevated basal UCP-1 expression, which was dependent on the activity of the orphan nuclear receptor ERRa, highlighting a novel role for ERRa in human brown fat. Thus fMSCs represent a useful in vitro model for human adipogenesis, and provide opportunities to study the stages prior to commitment to the adipocyte lineage. They also offer invaluable in- sights into the characteristics of human brown fat.
