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
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
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
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 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
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
Objective:To explore the anti-obesity effects and the mechanism of action of Monascus pilosus(M.pilosus)-fermented black soybean(MFBS)extracts(MFBSE)and MFBS powders(MFBSP)in adipocytes and high-fat diet(HFD)-induced ...Objective:To explore the anti-obesity effects and the mechanism of action of Monascus pilosus(M.pilosus)-fermented black soybean(MFBS)extracts(MFBSE)and MFBS powders(MFBSP)in adipocytes and high-fat diet(HFD)-induced obese mice,respectively.Methods:Black soybean was fermented with M.pilosus,and the main constituents in MFBS were analyzed by HPLC analysis.In vitro,MFBSE were examined for anti-adipogenic effects using Oil-Red O staining.In vivo,mice were fed a normal-fat diet(NFD)control,HFD control or HFD containing 1 g/kg MFBSP for 12 weeks,and then body weight gain and tissues weight measured.Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects.Results:MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity.MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice.MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes,such as peroxisome proliferator-activated receptorγ(PPARγ),fatty acid-binding protein 4(FABP4),and fatty acid synthase(FAS),in adipocytes and in white adipose tissue(WAT)of HFD-induced obese mice.Conclusions:These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFDinduced obese mice.展开更多
Modified Si-Miao-San(mS MS) is composed of Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Coptidis Semen Coicis and Atractylodes Rhizome. The prescription is used for the management of diabetes and insulin resistance ...Modified Si-Miao-San(mS MS) is composed of Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Coptidis Semen Coicis and Atractylodes Rhizome. The prescription is used for the management of diabetes and insulin resistance in the clinic. This study aims to investigate its regulation of glucose disposal in adipocytes. Differentiated 3T3-L1 adipocytes were stimulated with conditioned medium derived from activated macrophages to induce insulin resistance and observed the effects of Mac-CM on insulin-mediated glucose uptake along the insulin receptor substrate-1/PI3K/Akt signaling pathway. Moreover, its regulation of AMPK phosphorylation was also investigated. mS MS enhanced AMPK phosphorylation and promoted basal glucose uptake in adipocytes; mS MS inhibited NF-κB activation by reducing P65 phosphorylation and improved insulin-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to the restoration of insulin-mediated glucose uptake when cells were exposed to inflammatory stimulation. These beneficial effects were diminished in the presence of the AMPK inhibitor compound C. mS MS positively regulated AMPK activity, and this action contributed to improving insulin PI3 K signaling by the beneficial regulation of IRS-1 function through inhibition of inflammation in adipocytes.展开更多
Background:Meat quality is largely driven by fat deposition,which is regulated by several genes and signaling pathways.The cyclic adenosine monophosphate(cAMP)-regulated transcriptional coactivator 3(CRTC3)is a coacti...Background:Meat quality is largely driven by fat deposition,which is regulated by several genes and signaling pathways.The cyclic adenosine monophosphate(cAMP)-regulated transcriptional coactivator 3(CRTC3)is a coactivator of cAMP response element binding protein(CREB)that mediates the function of protein kinase A(PKA)signaling pathway and is involved in various biological processes including lipid and energy metabolism.However,the effects of CRTC3 on the metabolome and transcriptome of porcine subcutaneous adipocytes have not been studied yet.Here,we tested whether porcine CRTC3 expression would be related to fat deposition in Heigai pigs(a local fatty breed in China)and Duroc×Landrace×Yorkshire(DLY,a lean breed)pigs in vivo.The effects of adenovirus-induced CRTC3 overexpression on the metabolomic and transcriptomic profiles of subcutaneous adipocytes were also determined in vitro by performing mass spectrometry-based metabolomics combined with RNA sequencing(RNA-seq).Results:Porcine CRTC3 expression is associated with fat deposition in vivo.In addition,CRTC3 overexpression increased lipid accumulation and the expression of mature adipocyte-related genes in cultured porcine subcutaneous adipocytes.According to the metabolomic analysis,CRTC3 overexpression induced significant changes in adipocyte lipid,amino acid and nucleotide metabolites in vitro.The RNA-seq analysis suggested that CRTC3 overexpression alters the expression of genes and pathways involved in adipogenesis,fatty acid metabolism and glycerophospholipid metabolism in vitro.Conclusions:We identified significant alterations in the metabolite composition and the expression of genes and pathways involved in lipid metabolism in CRTC3-overexpressing adipocytes.Our results suggest that CRTC3 might play an important regulatory role in lipid metabolism and thus affects lipid accumulation in porcine subcutaneous adipocytes.展开更多
Objective: To examine whether Caulerpa okamurae ethanolic extract(COE) could inhibit obesitymediated inflammation, improve glucose metabolism and increase insulin sensitivity, using in vitro cell models of RAW 264.7 m...Objective: To examine whether Caulerpa okamurae ethanolic extract(COE) could inhibit obesitymediated inflammation, improve glucose metabolism and increase insulin sensitivity, using in vitro cell models of RAW 264.7 macrophages and 3 T3-L1 adipocytes.Methods: We cocultured 3 T3-L1 adipocytes in direct contact with lipopolysaccharide-stimulated RAW264.7 macrophages and induced insulin resistance in 3 T3-L1 adipocytes with tumor necrosis factor-a(TNF-a) in the presence or absence of 250 mg/m L of COE. We investigated various markers of inflammation, glucose regulation and insulin sensitivity in these models using Griess reagent to measure nitric oxide(NO) production, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose to measure glucose uptake, Western blot analysis to quantify protein expression and reverse transcriptasepolymerase chain reaction to evaluate m RNA expression.Results: We found that COE(250 mg/m L) significantly inhibited the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages by downregulating NO production, nitric oxide synthase 2 expression and nuclear translocation of nuclear factor-j B. COE also showed similar anti-inflammatory activity in coculture, along with decreased TNF-a, interleukin-6 and monocyte chemoattractant protein m RNA expression. In addition, COE also improved glucose uptake in coculture by upregulating glucose transporter-4(GLUT-4) and adiponectin and reducing serine phosphorylation of insulin receptor substrate-1(IRS1). In the TNF-a-induced insulin resistance model of 3 T3-L1 adipocytes, COE significantly improved both basal and insulin-stimulated glucose uptake, accompanied by phosphorylation of IRS1 at tyrosine 632, phospho-50 adenosine monophosphate-activated protein kinase a and glycogen synthase kinase-3 b(Ser9) as well as upregulation of GLUT-4.Conclusion: Together, these findings suggest that COE has potential to treat or prevent obesity-induced metabolic disorders.展开更多
Ligustri lucidi Fructus is a traditional Chinese medicine and possesses various bioactivities,including hypoglycemic effect.Ligustrum lucidum Ait flowers are poorly investigated.Thus,we hypothesized that L.lucidum flo...Ligustri lucidi Fructus is a traditional Chinese medicine and possesses various bioactivities,including hypoglycemic effect.Ligustrum lucidum Ait flowers are poorly investigated.Thus,we hypothesized that L.lucidum flowers also could have hypoglycemic effect.Chemical composition and glucose uptake effect of L.lucidum flowers on 3T3-L1 adipocytes were investigated.In this study,the components of L.lucidum flowers were investigated by various chromatographic and spectroscopic methods and the effects of L.lucidum flowers on the induction of glucose uptake were investigated by 3T3-L1 adipocytes.Seven compounds were isolated and identified from L.lucidum flowers,including ursolic acid(1),kaempferol-7-O-α-Lrhamnoside(2,KR),β-sitosterol(3),β-daucosterol(4),kaempferitrin(5,KF),10-hydroxy oleuropein(6,HO),and kaempferol-3-O-β-D-glucopyranoside-7-α-L-rhamnopyranoside(7,KGR).The results of glucose uptake showed that total extract(TE),KR,KF and HO from L.lucidum flowers significantly enhanced glucose uptake.This study demonstrated that compounds 2,5-7 were isolated for the first time from this plant and compounds 2 and 7 were isolated for the first time in genus Ligustrum,L.lucidum flowers,KR,KF and HO may possess potential hypoglycemic effect.展开更多
BACKGROUND When combined with vanadium salts,catecholamines strongly activate glucose uptake in rat and mouse adipocytes.AIM To test whether catecholamines activate glucose transport in human adipocytes.METHODS The up...BACKGROUND When combined with vanadium salts,catecholamines strongly activate glucose uptake in rat and mouse adipocytes.AIM To test whether catecholamines activate glucose transport in human adipocytes.METHODS The uptake of 2-deoxyglucose(2-DG)was measured in adipocytes isolated from pieces of abdominal subcutaneous tissue removed from women undergoing reconstructive surgery.Pharmacological approaches with amine oxidase inhibitors,adrenoreceptor agonists and antioxidants were performed to unravel the mechanisms of action of noradrenaline or adrenaline(also named epinephrine).RESULTS In human adipocytes,45-min incubation with 100μmol/L adrenaline or noradrenaline activated 2-DG uptake up to more than one-third of the maximal response to insulin.This stimulation was not reproduced with millimolar doses of dopamine or serotonin and was not enhanced by addition of vanadate to the incubation medium.Among various natural amines and adrenergic agonists tested,no other molecule was more efficient than adrenaline and noradrenaline in stimulating 2-DG uptake.The effect of the catecholamines was not impaired by pargyline and semicarbazide,contrarily to that of benzylamine or methylamine,which are recognized substrates of semicarbazide-sensitive amine oxidase.Hydrogen peroxide at 1 mmol/L activated hexose uptake but not pyrocatechol or benzoquinone,and only the former was potentiated by vanadate.Catalase and the phosphoinositide 3-kinase inhibitor wortmannin inhibited adrenaline-induced activation of 2-DG uptake.CONCLUSION High doses of catecholamines exert insulin-like actions on glucose transport in human adipocytes.At submillimolar doses,vanadium did not enhance this catecholamine activation of glucose transport.Consequently,this dismantles our previous suggestion to combine the metal ion with catecholamines to improve the benefit/risk ratio of vanadium-based antidiabetic approaches.展开更多
Objective： The leaves of Chromolaena odorata, a highly invasive shrub found growing wild worldwide, are traditionally used for wound healing. Due to its high flavonoid contents, we aimed to find a new appli- cation f...Objective： The leaves of Chromolaena odorata, a highly invasive shrub found growing wild worldwide, are traditionally used for wound healing. Due to its high flavonoid contents, we aimed to find a new appli- cation for this plant. Preliminary tests using its ethanolic leaf extract showed that it could suppress the accumulation of lipids in adipocytes. We therefore studied the anti-adipogenic effect of several C. odorata leaf extracts and the relationship between molecular structure and bio-activity of its isolated flavonoid constituents using 3T3-LI preadipocytes/adipocytes as a model. Methods： Three leaf extracts and thirteen flavonoids isolated from C odorata were tested for their effect on lipid accumulation in 3T3-L1 adipocytes using AdipoRed reagent, with quercetin as the positive con- trol. The effects of active flavonoids on the adipocytes were confirmed by oil red O staining and visualized under a light microscope.Results： n-Hexane and ethyl acetate extracts of C odorata leaves displayed anti-adipogenic activity. The latter extract was the more potent one, especially at 40 μg/mL. Four flavonoids, pectolinarigenin, kaemp- feride, 4,2＇-dihydroxy-4＇,5＇,6＇-trimethoxychalcone and dillenetin, exhibited significant, concentration- dependent inhibitory effects on lipid accumulation in 3T3-L1 adipocytes. The most potent flavonoid obtained in this study was 4,2＇-dihydroxy-4＇,5＇,6＇-trimethoxychalcone, which caused 75% and 90% inhi- bition of cellular lipid accumulation at 30 and 50μmol/L, respectively. Both kaempferide and 4,2＇-dihy droxy-4＇,5＇,6＇-trimethoxychalcone were major constituents in the ethyl acetate extract of this plant.Conclusion： C odorata leaves contained several flavonoids with anti-adipogenic effects against lipid accu- mulation in 3T3-L1 adipocytes. The plant, normally considered a useless weed, may actually provide an abundant source of biologically active flavonoids.展开更多
Mesenchymal stem cells(MSCs) derived from human induced pluripotent stem cells(hiPSCs) provide a novel source for generating adipocytes, thus opening new avenues for fundamental research and clinical medicine. We pres...Mesenchymal stem cells(MSCs) derived from human induced pluripotent stem cells(hiPSCs) provide a novel source for generating adipocytes, thus opening new avenues for fundamental research and clinical medicine. We present the adipogenic potential of hiPSCs and the various methods to derive hiPSC-MSCs. We discuss the main characteristic of hiPSC-MSCs, which is their low adipogenic capacity as compared to adult-MSCs. Finally, we propose several hypotheses to explanation this feature, underlying a potential critical role of the micro-environment. We favour the hypothesis that the range of factors or culture conditions required to induce adipocyte differentiation of MSCs derived from adult tissues and from embryonic-like cells could differ.展开更多
AIM To study complete dose-dependent effects of obestatin on lipolytic and glucose transport activities in human adipocyte preparations highly responsive to insulin.METHODS Adipocytes were prepared by liberase digesti...AIM To study complete dose-dependent effects of obestatin on lipolytic and glucose transport activities in human adipocyte preparations highly responsive to insulin.METHODS Adipocytes were prepared by liberase digestion from subcutaneous abdominal adipose tissue obtained from overweight subjects undergoing plastic surgery. The index of lipolytic activity was the glycerol released in the incubation medium, while glucose transport was assessed by [~3H]-2-deoxyglucose uptake assay.RESULTS When tested from 0.1 nmol/L to 1 μmol/L, obestatin did not stimulate glycerol release; it did not inhibit the lipolytic effect of isoprenaline and did not alter the insulin antilipolytic effect. Obestatin hardly activated glucose transport at 1 μmol/L only. Moreover, the obestatin stimulation effect was clearly lower than the threefold increase induced by insulin 100 nmol/L.CONCLUSION Low doses of obestatin cannot directly influence lipolysis and glucose uptake in human fat cells.展开更多
Objective:To investigate the crude extracts of Ichnacarpus frutescens(I.frutescens) for antiobesity effect.Methods:Leaves of I.frutescens were sequentially extracted with hexane,ethyl acetate, and methanol and their e...Objective:To investigate the crude extracts of Ichnacarpus frutescens(I.frutescens) for antiobesity effect.Methods:Leaves of I.frutescens were sequentially extracted with hexane,ethyl acetate, and methanol and their effect on viability of 3T3-L1 preadipocytes were evaluated.Based on this the apoptosis on preadipocytes was confirmed by DMA fragmentation and LDH(Lactate dehydrogenase) leakage assays.Anti-adipogenesis was performed by oil red O(ORO) staining and free glycerol release in the medium of differentiated adipocytes.Results:The hexane extract of I.frutescens(IFHE) inhibited cell viability in a time- and dose-related manner.An increased release of LDH.as a marker of membrane integrity,was observed at a dose of 200μg/mL The discontinuous DMA fragments on agarose gel electrophoresis showed the apoptotic effect of the IFHE.Morphological observations of cells stained with ORG showed a decrease in cellular lipid content at the concentrations tested compared to the induced control cells.In the experiment of lipolytic activity,treatment with IFHE enhanced glycerol secretion with the rates of approximately 28%.55%,and 46%at the concentrations of 100,200 and 300μg/mL,respectively.Conclusions: The observed properties clearly revealed the medicinal property of I.frulescens in the treatment of obesity.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
Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained wi...Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained with OilRed-O staining to confirm adipogenesis.The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay,intracellular reactive oxygen species generation through flow cytometry,and morphologically through confocal microscopy using propidium iodide,4,6-diamino-2-phenylindol dihydrochloride,and 2’,7’-dichlorofluorescein diacetate dyes.The uptake of fluorescent glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy.Results:MTT assay showed that the cell survival rate was(28.00±3.00)%,(92.33±2.60)%,and(71.34±2.10)%in the presence of 2 mM H2O2,AbPI alone,and AbPI and H2O2 both,respectively,in comparison to the control.Oil-Red-O staining indicated that Ab PI enhanced adipogenesis.AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone,and showed insulinsensitizing effect in the presence of insulin,but failed to stimulate the uptake in the absence of insulin.Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon Ab PI treatment.Confocal microscopy showed that the damaged cell population rose to 3.50%,117.84%,and 261.50%in the presence of Ab PI alone,AbPI with H2O2,and H2O2 alone,respectively.Conclusions:The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.展开更多
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 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 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 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.
基金the support of the "Cooperative Research Program for Agriculture Science & Technology Development (Project No.PJ009582)" of the Rural Development Administration.Republic of Korea
文摘Objective:To explore the anti-obesity effects and the mechanism of action of Monascus pilosus(M.pilosus)-fermented black soybean(MFBS)extracts(MFBSE)and MFBS powders(MFBSP)in adipocytes and high-fat diet(HFD)-induced obese mice,respectively.Methods:Black soybean was fermented with M.pilosus,and the main constituents in MFBS were analyzed by HPLC analysis.In vitro,MFBSE were examined for anti-adipogenic effects using Oil-Red O staining.In vivo,mice were fed a normal-fat diet(NFD)control,HFD control or HFD containing 1 g/kg MFBSP for 12 weeks,and then body weight gain and tissues weight measured.Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects.Results:MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity.MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice.MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes,such as peroxisome proliferator-activated receptorγ(PPARγ),fatty acid-binding protein 4(FABP4),and fatty acid synthase(FAS),in adipocytes and in white adipose tissue(WAT)of HFD-induced obese mice.Conclusions:These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFDinduced obese mice.
基金supported by the National Natural Science Foundation of China(Nos.81072976,81173623)
文摘Modified Si-Miao-San(mS MS) is composed of Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Coptidis Semen Coicis and Atractylodes Rhizome. The prescription is used for the management of diabetes and insulin resistance in the clinic. This study aims to investigate its regulation of glucose disposal in adipocytes. Differentiated 3T3-L1 adipocytes were stimulated with conditioned medium derived from activated macrophages to induce insulin resistance and observed the effects of Mac-CM on insulin-mediated glucose uptake along the insulin receptor substrate-1/PI3K/Akt signaling pathway. Moreover, its regulation of AMPK phosphorylation was also investigated. mS MS enhanced AMPK phosphorylation and promoted basal glucose uptake in adipocytes; mS MS inhibited NF-κB activation by reducing P65 phosphorylation and improved insulin-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to the restoration of insulin-mediated glucose uptake when cells were exposed to inflammatory stimulation. These beneficial effects were diminished in the presence of the AMPK inhibitor compound C. mS MS positively regulated AMPK activity, and this action contributed to improving insulin PI3 K signaling by the beneficial regulation of IRS-1 function through inhibition of inflammation in adipocytes.
基金The project was partially supported by the National Natural Science Foundation of China(31722053,31672427)the Natural Science Foundation of Zhejiang Province(LR17C170001)the“Hundred Talents Program”funding from Zhejiang University awarded to TZS.
文摘Background:Meat quality is largely driven by fat deposition,which is regulated by several genes and signaling pathways.The cyclic adenosine monophosphate(cAMP)-regulated transcriptional coactivator 3(CRTC3)is a coactivator of cAMP response element binding protein(CREB)that mediates the function of protein kinase A(PKA)signaling pathway and is involved in various biological processes including lipid and energy metabolism.However,the effects of CRTC3 on the metabolome and transcriptome of porcine subcutaneous adipocytes have not been studied yet.Here,we tested whether porcine CRTC3 expression would be related to fat deposition in Heigai pigs(a local fatty breed in China)and Duroc×Landrace×Yorkshire(DLY,a lean breed)pigs in vivo.The effects of adenovirus-induced CRTC3 overexpression on the metabolomic and transcriptomic profiles of subcutaneous adipocytes were also determined in vitro by performing mass spectrometry-based metabolomics combined with RNA sequencing(RNA-seq).Results:Porcine CRTC3 expression is associated with fat deposition in vivo.In addition,CRTC3 overexpression increased lipid accumulation and the expression of mature adipocyte-related genes in cultured porcine subcutaneous adipocytes.According to the metabolomic analysis,CRTC3 overexpression induced significant changes in adipocyte lipid,amino acid and nucleotide metabolites in vitro.The RNA-seq analysis suggested that CRTC3 overexpression alters the expression of genes and pathways involved in adipogenesis,fatty acid metabolism and glycerophospholipid metabolism in vitro.Conclusions:We identified significant alterations in the metabolite composition and the expression of genes and pathways involved in lipid metabolism in CRTC3-overexpressing adipocytes.Our results suggest that CRTC3 might play an important regulatory role in lipid metabolism and thus affects lipid accumulation in porcine subcutaneous adipocytes.
基金supported by a grant from the Basic Science Research Program(2015R1D1A1A09060557)through the National Research Foundation(NRF)funded by the Ministry of Education,Science and Technology,Republic of Korea.
文摘Objective: To examine whether Caulerpa okamurae ethanolic extract(COE) could inhibit obesitymediated inflammation, improve glucose metabolism and increase insulin sensitivity, using in vitro cell models of RAW 264.7 macrophages and 3 T3-L1 adipocytes.Methods: We cocultured 3 T3-L1 adipocytes in direct contact with lipopolysaccharide-stimulated RAW264.7 macrophages and induced insulin resistance in 3 T3-L1 adipocytes with tumor necrosis factor-a(TNF-a) in the presence or absence of 250 mg/m L of COE. We investigated various markers of inflammation, glucose regulation and insulin sensitivity in these models using Griess reagent to measure nitric oxide(NO) production, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose to measure glucose uptake, Western blot analysis to quantify protein expression and reverse transcriptasepolymerase chain reaction to evaluate m RNA expression.Results: We found that COE(250 mg/m L) significantly inhibited the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages by downregulating NO production, nitric oxide synthase 2 expression and nuclear translocation of nuclear factor-j B. COE also showed similar anti-inflammatory activity in coculture, along with decreased TNF-a, interleukin-6 and monocyte chemoattractant protein m RNA expression. In addition, COE also improved glucose uptake in coculture by upregulating glucose transporter-4(GLUT-4) and adiponectin and reducing serine phosphorylation of insulin receptor substrate-1(IRS1). In the TNF-a-induced insulin resistance model of 3 T3-L1 adipocytes, COE significantly improved both basal and insulin-stimulated glucose uptake, accompanied by phosphorylation of IRS1 at tyrosine 632, phospho-50 adenosine monophosphate-activated protein kinase a and glycogen synthase kinase-3 b(Ser9) as well as upregulation of GLUT-4.Conclusion: Together, these findings suggest that COE has potential to treat or prevent obesity-induced metabolic disorders.
基金This work was supported by National Natural Science Foundation of China(31900292)Key Project in Science and Technology Agency of Henan Province(182102410083).
文摘Ligustri lucidi Fructus is a traditional Chinese medicine and possesses various bioactivities,including hypoglycemic effect.Ligustrum lucidum Ait flowers are poorly investigated.Thus,we hypothesized that L.lucidum flowers also could have hypoglycemic effect.Chemical composition and glucose uptake effect of L.lucidum flowers on 3T3-L1 adipocytes were investigated.In this study,the components of L.lucidum flowers were investigated by various chromatographic and spectroscopic methods and the effects of L.lucidum flowers on the induction of glucose uptake were investigated by 3T3-L1 adipocytes.Seven compounds were isolated and identified from L.lucidum flowers,including ursolic acid(1),kaempferol-7-O-α-Lrhamnoside(2,KR),β-sitosterol(3),β-daucosterol(4),kaempferitrin(5,KF),10-hydroxy oleuropein(6,HO),and kaempferol-3-O-β-D-glucopyranoside-7-α-L-rhamnopyranoside(7,KGR).The results of glucose uptake showed that total extract(TE),KR,KF and HO from L.lucidum flowers significantly enhanced glucose uptake.This study demonstrated that compounds 2,5-7 were isolated for the first time from this plant and compounds 2 and 7 were isolated for the first time in genus Ligustrum,L.lucidum flowers,KR,KF and HO may possess potential hypoglycemic effect.
文摘BACKGROUND When combined with vanadium salts,catecholamines strongly activate glucose uptake in rat and mouse adipocytes.AIM To test whether catecholamines activate glucose transport in human adipocytes.METHODS The uptake of 2-deoxyglucose(2-DG)was measured in adipocytes isolated from pieces of abdominal subcutaneous tissue removed from women undergoing reconstructive surgery.Pharmacological approaches with amine oxidase inhibitors,adrenoreceptor agonists and antioxidants were performed to unravel the mechanisms of action of noradrenaline or adrenaline(also named epinephrine).RESULTS In human adipocytes,45-min incubation with 100μmol/L adrenaline or noradrenaline activated 2-DG uptake up to more than one-third of the maximal response to insulin.This stimulation was not reproduced with millimolar doses of dopamine or serotonin and was not enhanced by addition of vanadate to the incubation medium.Among various natural amines and adrenergic agonists tested,no other molecule was more efficient than adrenaline and noradrenaline in stimulating 2-DG uptake.The effect of the catecholamines was not impaired by pargyline and semicarbazide,contrarily to that of benzylamine or methylamine,which are recognized substrates of semicarbazide-sensitive amine oxidase.Hydrogen peroxide at 1 mmol/L activated hexose uptake but not pyrocatechol or benzoquinone,and only the former was potentiated by vanadate.Catalase and the phosphoinositide 3-kinase inhibitor wortmannin inhibited adrenaline-induced activation of 2-DG uptake.CONCLUSION High doses of catecholamines exert insulin-like actions on glucose transport in human adipocytes.At submillimolar doses,vanadium did not enhance this catecholamine activation of glucose transport.Consequently,this dismantles our previous suggestion to combine the metal ion with catecholamines to improve the benefit/risk ratio of vanadium-based antidiabetic approaches.
基金supported by a grant from Thailand Graduate Institute of Science and Technology(TGIST)(grant number:01-54-007)Nano-Cosmeceuticals Laboratory,National Nan-otechnology Center(NANOTEC)National Science and Technology Development Agency(NSTDA),Thailand
文摘Objective： The leaves of Chromolaena odorata, a highly invasive shrub found growing wild worldwide, are traditionally used for wound healing. Due to its high flavonoid contents, we aimed to find a new appli- cation for this plant. Preliminary tests using its ethanolic leaf extract showed that it could suppress the accumulation of lipids in adipocytes. We therefore studied the anti-adipogenic effect of several C. odorata leaf extracts and the relationship between molecular structure and bio-activity of its isolated flavonoid constituents using 3T3-LI preadipocytes/adipocytes as a model. Methods： Three leaf extracts and thirteen flavonoids isolated from C odorata were tested for their effect on lipid accumulation in 3T3-L1 adipocytes using AdipoRed reagent, with quercetin as the positive con- trol. The effects of active flavonoids on the adipocytes were confirmed by oil red O staining and visualized under a light microscope.Results： n-Hexane and ethyl acetate extracts of C odorata leaves displayed anti-adipogenic activity. The latter extract was the more potent one, especially at 40 μg/mL. Four flavonoids, pectolinarigenin, kaemp- feride, 4,2＇-dihydroxy-4＇,5＇,6＇-trimethoxychalcone and dillenetin, exhibited significant, concentration- dependent inhibitory effects on lipid accumulation in 3T3-L1 adipocytes. The most potent flavonoid obtained in this study was 4,2＇-dihydroxy-4＇,5＇,6＇-trimethoxychalcone, which caused 75% and 90% inhi- bition of cellular lipid accumulation at 30 and 50μmol/L, respectively. Both kaempferide and 4,2＇-dihy droxy-4＇,5＇,6＇-trimethoxychalcone were major constituents in the ethyl acetate extract of this plant.Conclusion： C odorata leaves contained several flavonoids with anti-adipogenic effects against lipid accu- mulation in 3T3-L1 adipocytes. The plant, normally considered a useless weed, may actually provide an abundant source of biologically active flavonoids.
文摘Mesenchymal stem cells(MSCs) derived from human induced pluripotent stem cells(hiPSCs) provide a novel source for generating adipocytes, thus opening new avenues for fundamental research and clinical medicine. We present the adipogenic potential of hiPSCs and the various methods to derive hiPSC-MSCs. We discuss the main characteristic of hiPSC-MSCs, which is their low adipogenic capacity as compared to adult-MSCs. Finally, we propose several hypotheses to explanation this feature, underlying a potential critical role of the micro-environment. We favour the hypothesis that the range of factors or culture conditions required to induce adipocyte differentiation of MSCs derived from adult tissues and from embryonic-like cells could differ.
文摘AIM To study complete dose-dependent effects of obestatin on lipolytic and glucose transport activities in human adipocyte preparations highly responsive to insulin.METHODS Adipocytes were prepared by liberase digestion from subcutaneous abdominal adipose tissue obtained from overweight subjects undergoing plastic surgery. The index of lipolytic activity was the glycerol released in the incubation medium, while glucose transport was assessed by [~3H]-2-deoxyglucose uptake assay.RESULTS When tested from 0.1 nmol/L to 1 μmol/L, obestatin did not stimulate glycerol release; it did not inhibit the lipolytic effect of isoprenaline and did not alter the insulin antilipolytic effect. Obestatin hardly activated glucose transport at 1 μmol/L only. Moreover, the obestatin stimulation effect was clearly lower than the threefold increase induced by insulin 100 nmol/L.CONCLUSION Low doses of obestatin cannot directly influence lipolysis and glucose uptake in human fat cells.
文摘Objective:To investigate the crude extracts of Ichnacarpus frutescens(I.frutescens) for antiobesity effect.Methods:Leaves of I.frutescens were sequentially extracted with hexane,ethyl acetate, and methanol and their effect on viability of 3T3-L1 preadipocytes were evaluated.Based on this the apoptosis on preadipocytes was confirmed by DMA fragmentation and LDH(Lactate dehydrogenase) leakage assays.Anti-adipogenesis was performed by oil red O(ORO) staining and free glycerol release in the medium of differentiated adipocytes.Results:The hexane extract of I.frutescens(IFHE) inhibited cell viability in a time- and dose-related manner.An increased release of LDH.as a marker of membrane integrity,was observed at a dose of 200μg/mL The discontinuous DMA fragments on agarose gel electrophoresis showed the apoptotic effect of the IFHE.Morphological observations of cells stained with ORG showed a decrease in cellular lipid content at the concentrations tested compared to the induced control cells.In the experiment of lipolytic activity,treatment with IFHE enhanced glycerol secretion with the rates of approximately 28%.55%,and 46%at the concentrations of 100,200 and 300μg/mL,respectively.Conclusions: The observed properties clearly revealed the medicinal property of I.frulescens in the treatment of obesity.
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Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained with OilRed-O staining to confirm adipogenesis.The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay,intracellular reactive oxygen species generation through flow cytometry,and morphologically through confocal microscopy using propidium iodide,4,6-diamino-2-phenylindol dihydrochloride,and 2’,7’-dichlorofluorescein diacetate dyes.The uptake of fluorescent glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy.Results:MTT assay showed that the cell survival rate was(28.00±3.00)%,(92.33±2.60)%,and(71.34±2.10)%in the presence of 2 mM H2O2,AbPI alone,and AbPI and H2O2 both,respectively,in comparison to the control.Oil-Red-O staining indicated that Ab PI enhanced adipogenesis.AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone,and showed insulinsensitizing effect in the presence of insulin,but failed to stimulate the uptake in the absence of insulin.Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon Ab PI treatment.Confocal microscopy showed that the damaged cell population rose to 3.50%,117.84%,and 261.50%in the presence of Ab PI alone,AbPI with H2O2,and H2O2 alone,respectively.Conclusions:The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.
