An increasing number of studies have characterized the bone as an endocrine organ,and that bone secreted factors may not only regulate local bone remodeling,but also other tissues and whole-body metabolic functions.Th...An increasing number of studies have characterized the bone as an endocrine organ,and that bone secreted factors may not only regulate local bone remodeling,but also other tissues and whole-body metabolic functions.The precise nature of these regulatory factors and their roles at bridging the bone,bone marrow adipose tissue,extramedullary body fat and whole-body energy homeostasis are being explored.In this study,we report that KIAA1199,a secreted factor produced from bone and bone marrow,previously described as an inhibitor of bone formation,also plays a role at promoting adipogenesis.KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue,subcutaneous and visceral fat tissue mass,blood cholesterol,triglycerides,free fatty acids and glycerol,as well as improved insulin sensitivity in skeletal muscle,liver and fat.Moreover,these mice are protected from the detrimental effects of high-fat diet feeding,with decreased obesity,lower blood glucose and glucose tolerance,as well as decreased adipose tissue inflammation,insulin resistance and hepatic steatosis.In human studies,plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol,triglycerides,free fatty acids,glycerol,fasting glucose and HOMA-IR.Mechanistically,KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT/ERK signaling.These findings provide evidence for the role of bone secreted factors on coupling bone,fat and whole-body energy homeostasis.展开更多
Adipose-derived mesenchymal stem cells(ADSCs)represent a readily accessible and important source of mesenchymal stem cells(MSCs)capable of multilineage differentiation.The Hippo signaling pathway effector YAP has emer...Adipose-derived mesenchymal stem cells(ADSCs)represent a readily accessible and important source of mesenchymal stem cells(MSCs)capable of multilineage differentiation.The Hippo signaling pathway effector YAP has emerged as a pivotal regulator of stem cell fate,yet the specific molecular mechanism by which it modulates lipogenic differentiation of ADSCs has not been clearly defined.In this study,goat ADSCs(gADSCs)isolated from Albas goats in Inner Mongolia were used to investigate the role of YAP1 in adipogenic differentiation.Overexpression of YAP1 significantly promoted the differentiation of ADSCs into adipocytes,an effect accompanied by up-regulation of LATS2 and activation of the negative feedback loop of the Hippo signaling pathway.Elevated LATS2 expression induced YAP phosphorylation,leading to reduced nuclear levels of YAP and TAZ and their subsequent accumulation in the cytoplasm.YAP1 overexpression up-regulated LATS2 expression,which,in turn,enhanced the adipogenic differentiation of ADSCs.This pro-adipogenic effect of YAP1 was dependent on LATS2 kinase activity.These findings indicate that overexpression of YAP1 promotes ADSC adipogenesis by inducing LATS2 expression and activating the Hippo pathway negative feedback loop.Elucidating the molecular role of YAP in ADSC lipogenic differentiation holds great significance for regulating stem cell fate,treating metabolic disorders,and promoting hair follicle growth.展开更多
Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs r...Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear.Lysine 2-hydroxyisobutyrylation(Khib),is a novel protein post-translational modification(PTM),which play an important role in transcription,energy metabolism and metastasis of cancer cells,but its role in adipogenesis and fat accumulation has not been shown.Results In this study,we first analyzed the modification levels of acetylation(Kac),Khib,crotonylation(Kcr)and succinylation(Ksu)of fibro-adipogenic progenitors(FAPs),myogenic precursors(Myo)and mesenchymal stem cells(MSCs)with varied differentiation potential,and found that only Khib modification in FAPs was significantly higher than that in MSCs.Consistently,in parallel with its regulatory enzymes lysine acetyltransferase 5(KAT5)and histone deacetylase 2(HDAC2)protein levels,the Khib levels increased quadratically(P<0.01)during adipogenic differentiation of FAPs.KAT5 knockdown in FAPs inhibited adipogenic differentiation,while HDAC2 knockdown enhanced adipogenic differentiation.We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs(Laiwu pigs)and lean-type pigs(Duroc pigs),respectively.Accordingly,the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese-and lean-type pigs.Conclusions From the perspective of protein translational modification,we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs,and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.展开更多
Objective:Pelvic organ prolapse(POP)is a common condition in postmenopausal women,with an increasing prevalence due to aging.Some women experience POP recurrence after surgical treatment,significantly affecting their ...Objective:Pelvic organ prolapse(POP)is a common condition in postmenopausal women,with an increasing prevalence due to aging.Some women experience POP recurrence after surgical treatment,significantly affecting their physical and mental health.The uterosacral ligament is a critical pelvic support structure.This study aims to investigate the molecular pathological changes in the uterosacral ligament of postmenopausal women with recurrent POP using transcriptomic analysis.Methods:Transcriptomic data of uterosacral ligament tissues were obtained from the public dataset GSE28660,which includes samples from 4 postmenopausal women with recurrent POP,4 with primary POP,and 4 without POP.Differentially expressed genes(DEGs)were identified between recurrent POP and both primary and non-POP groups.Further analysis included intersection analysis of DEGs,gene ontology enrichment,protein protein interaction(PPI)network construction,gene set enrichment analysis(GSEA),single-sample GSEA,and xCell immune cell infiltration analysis to explore molecular pathological changes in recurrent POP.Additionally,histological and molecular differences in the uterosacral ligament were compared between simulated vaginal delivery(SVD)rat models with and without ovariectomy.Results:Compared with primary POP and non-POP groups,recurrent POP exhibited activation of adipogenesis and inflammation-related pathways,while pathways related to muscle proliferation and contraction were downregulated in the uterosacral ligament.Nine key DEGs(ADIPOQ,FABP4,IL-6,LIPE,LPL,PCK1,PLIN1,PPARG,and CD36)were identified,with most enriched in the peroxisome proliferator-activated receptor(PPAR)signaling pathway.These genes were significantly correlated with lipid accumulation,monocyte infiltration,and neutrophil infiltration in the uterosacral ligament.Urodynamic testing revealed that the bladder leak point pressure was significantly higher in ovariectomized SVD rats,both of which had higher values than the sham group.Masson staining showed pronounced adipogenesis in the uterosacral ligament of ovariectomized SVD rats,along with reduced collagen and muscle fibers compared to the sham and non ovariectomized SVD groups.Furthermore,real-time RT-PCR confirmed significantly elevated expression of key DEGs,including ADIPOQ,IL-6,PCK1,and PLIN1,in the uterosacral ligaments of ovariectomized SVD rats.Conclusion:Adipogenesis and inflammation in the uterosacral ligament may contribute to its reduced supportive function,potentially leading to recurrence POP in postmenopausal women.展开更多
Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential r...Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential role. To explore the function of Dnmt1, its expression was first profiled during the course of adipocyte differentiation of 3T3-L1 cells. The results revealed a dynamic regulation of its expression at the initiation stage. Knockdown of Dnmt1 compromised the differentiation process and decreased lipid production within the cells. To the aspect of epigenetic regulation, promoter methylation of Cdkn1a was significantly increased at the initiation stage of the differentiation, accompanied by decreased Cdkn1a expression. Furthermore, knockdown of Dnmt1 led to an increased Cdkn1a expression, indicating that Dnmt1 inhibits Cdkn1a expression by promoter methylation. Furthermore, we found that knockdown of Cdkn1a up-regulated the expression of PPARγ and resulted in enhanced adipocyte differentiation. In summary, our results demonstrated that Dnmt1 regulated the process of adipogenesis by methylation of Cdkn1a promoter, suggesting that Cdkn1a played a fundamental role in the prevention of adipocyte hyperplasia.展开更多
Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation...Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation of 3T3-L1 cells requires two processes： the licensing of an adipogenesis gene-expression program within a particular growth-arrest stage, i.e., the contact-inhibition stage, and then the execution of this program in a cell-cycle-independent manner, by which the licensed progenitors are differentiated into adipocytes in the presence of inducing factors. Our results showed that differentiation licensing of 3T3-L1 cells during the contact-inhibition stage involved epigenetic modifications such as DNA methylation and histone modifications, whereas disturbing these epigenetic modifications by DNA methylation inhibitors or RNAi during the contact-inhibition stage significantly reduced adipogenesis efficiency. More importantly, when these licensed 3T3-L1 cells were re-cultured under non-differentiating conditions or treated only with insulin, this adipogenesis commitment could be maintained from one cell generation to the next, whereby the licensed program could be activated in a cell-cycle-independent manner once these cells were subjected to adipo- genesis-inducing conditions. This result suggests that differentiation licensing and differentiation execution can be uncoupled and disparately linked to cell proliferation. Our findings deliver a new concept that cell-fate decision can be subdivided into at least two stages, licensing and execution, which might have different regulatory relationships with cell proliferation. In addition, this new concept may provide a clue for developing new strategies against obesity.展开更多
SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-bin...SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-binding protein a （C/EBPa） during adipocyte differentiation. C/EBPa, but not C/EBPap30, activated SIRT1 promoter in both HeLa cells and 3T3-L1 preadipocytes. Furthermore, C/EBPa upregulated SIRT1 mRNA and protein levels in HeLa cells and increased SIRT1 expression in a p53-independent manner in Soas2 cells. In preadipocytes, ectopic expression of C/EBPa upregulated SIRT1 protein level and knockdown of C/EBPa led to the decrease of SIRTI pro- tein level. Moreover, by promoter deletion analysis, gel shift assay and chromatin immunoprecipitation, we found that C/EBPa bound to the SIRT1 promoter at a consensus C/EBPα binding site. These data demonstrate that C/ EBPα regulates SIRT1 expression during adipogenesis by directly binding to the SIRT1 promoter.展开更多
Background:Excessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality,feed utilization,and reproduction.Abdominal fat deposition depends on the proliferation of preadipoc...Background:Excessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality,feed utilization,and reproduction.Abdominal fat deposition depends on the proliferation of preadipocytes and their maturation into adipocytes,which involves a cascade of regulatory molecules.Accumulating evidence has shown that microRNAs(miRNAs)serve as post-transcriptional regulators of adipogenic differentiation in mammals.However,the miRNA-mediated molecular mechanisms underlying abdominal fat deposition in chickens are still poorly understood.This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken abdominal adipogenesis.Results:We established a chicken model of abdominal adipocyte differentiation and analyzed miRNA and mRNA expression in abdominal adipocytes at different stages of differentiation(0,12,48,72,and 120 h).A total of 217 differentially expressed miRNAs(DE-miRNAs)and 3520 differentially expressed genes were identified.Target prediction of DE-miRNAs and functional enrichment analysis revealed that the differentially expressed targets were significantly enriched in lipid metabolism-related signaling pathways,including the PPAR signaling and MAPK signaling pathways.A candidate miRNA,gga-miR-106-5p,exhibited decreased expression during the proliferation and differentiation of abdominal preadipocytes and was downregulated in the abdominal adipose tissues of fat chickens compared to that of lean chickens.gga-miR-106-5p was found to inhibit the proliferation and adipogenic differentiation of chicken abdominal preadipocytes.A dual-luciferase reporter assay suggested that the KLF15 gene,which encodes a transcriptional factor,is a direct target of gga-miR-106-5p.gga-miR-106-5p suppressed the posttranscriptional activity of KLF15,which is an activator of abdominal preadipocyte proliferation and differentiation,as determined with gain-and loss-of-function experiments.Conclusions:gga-miR-106-5p functions as an inhibitor of abdominal adipogenesis by targeting the KLF15 gene in chickens.These findings not only improve our understanding of the specific functions of miRNAs in avian adipogenesis but also provide potential targets for the genetic improvement of excessive abdominal fat deposition in poultry.展开更多
Methyl tert-butyl ether (MTBE),as a widely used gasoline additive,is suspected of being environmentally toxic.MTBE accumulates mainly in adipose tissue,but its effect on obesity or obesity-related metabolic disorders ...Methyl tert-butyl ether (MTBE),as a widely used gasoline additive,is suspected of being environmentally toxic.MTBE accumulates mainly in adipose tissue,but its effect on obesity or obesity-related metabolic disorders has not been well understood yet.Therefore,we examined the effect of MTBE on the adipose function and the related metabolic processes with both 3T3-L1 cell line and C57BL/6J mice model.We found that exposure to MTBE at the environmental relevant concentration (100 μmol/L) could significantly induce differentiation of preadipocyte and disturb insulin-stimulated glucose uptake of mature adipocyte.The in vivo observation in male mice showed a positive correlation of visceral white adipose tissue (vWAT) expansion and cell size increase with MTBE treatment in 14 weeks.Glucose tolerance and insulin sensitivity tests demonstrated that MTBE at 1000 μg/(kg·day) disturbed the systemic glucose metabolism in a gender-specific manner,which might be partly attributed to the alterations of gut microbiota community at genus level with respect to Akkermansia,Clostridium XIVb,and Megamonas.In summary,our study characterized the effect of MTBE on adipose tissue function and glucose homeostasis in vitro and in vivo,and revealed that systemic disorders of the glucose metabolism might be modulated by the related gut microbiota.展开更多
It is generally agreed that adipocytes originate from mesenchymal stem cells in what can be divided into two processes:determination and differentiation.In the past decade,many factors associated with epigenetic signa...It is generally agreed that adipocytes originate from mesenchymal stem cells in what can be divided into two processes:determination and differentiation.In the past decade,many factors associated with epigenetic signals have been proved to be pivotal for the appropriate timing of adipogenesis progression.A large number of coregulators at critical gene promoters set up specific patterns of DNA methylation,histone acetylation and methylation,and nucleosome rearrangement,that act as an epigenetic code to modulate the correct progress of adipocyte differentiation and adipogenesis during adipogenesis.In this review,we focus on the functions and roles of epigenetic processes in preadipocyte differentiation and adipogenesis.展开更多
Background Long non-coding RNAs(lncRNAs)regulate numerous biological processes,including adipogenesis.Research on adipogenesis will assist in the treatment of human metabolic diseases and improve meat quality in lives...Background Long non-coding RNAs(lncRNAs)regulate numerous biological processes,including adipogenesis.Research on adipogenesis will assist in the treatment of human metabolic diseases and improve meat quality in livestock,such as the content of intramuscular fat(IMF).However,the significance of lncRNAs in intramuscular adipogenesis remains unclear.This research aimed to reveal the lncRNAs transcriptomic profiles in the process of bovine intramuscular adipogenesis and to identify the lncRNAs involved in the adipogenesis of bovine intramuscular adipocytes.Results In this research,a landscape of lncRNAs was identified with RNA-seq in bovine intramuscular adipocytes at four adipogenesis stages(0 d,3 d,6 d,and 9 d after differentiation).A total of 7035 lncRNAs were detected,including 3396 novel lncRNAs.Based on the results of differential analysis,co-expression analysis,and functional prediction,we focused on the bovine intramuscular adipogenesis-associated long non-coding RNA(BIANCR),a novel lncRNA that may have an important regulatory function.The knockdown of BIANCR inhibited proliferation and promoted apoptosis of intramuscular preadipocytes.Moreover,BIANCR knockdown inhibited intramuscular adipogenesis by regulating the ERK1/2 signaling pathway.Conclusion This study obtained the landscape of lncRNAs during adipogenesis in bovine intramuscular adipocytes.BIANCR plays a crucial role in adipogenesis through the ERK1/2 signaling pathway.The results are noteworthy for improving beef meat quality,molecular breeding,and metabolic disease research.展开更多
Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and...Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and apoptosis,in an MMP-independent manner.This study aimed to examine the role of TIMP-1 in adipogenesis of adipose-derived stem cells(ASCs)and the underlying mechanism.We knocked down the TIMP-1 gene in ASCs through lentiviral vectors encoding TIMP-1 small interfering RNA(siRNA),and then found that the knockdown of TIMP-1 in ASCs promoted the adipogenic differentiation of stem cells and inhibited the Wnt/β-catenin signaling pathway in ASCs.We also noted that mutant TIMP-1 without the inhibitory activity on MMPs promoted the activation of Wnt/β-catenin pathway as well as the recombinant wild type TIMP-1 did,which indicated that the effect of TIMP-1 on Wnt/β-catenin pathway was MMPindependent.Our study suggested that TIMP-1 negatively regulated the adipogenesis of ASCs via the Wnt/β-catenin signaling pathway in an MMP-independent manner.展开更多
Lipid metabolism and adipocyte differentiation are reglulated by networking of transcription factors. It is generally known that three factors, peroxisome proliferator-activated receptor y （PPARγ）, CCAAT/element-bi...Lipid metabolism and adipocyte differentiation are reglulated by networking of transcription factors. It is generally known that three factors, peroxisome proliferator-activated receptor y （PPARγ）, CCAAT/element-binding protein a （C/EBPa） and sterol regulatory element binding protein-1 （SREBP1）, play fundamental roles in metabolic pathways. And they are also important in adipocyte differentiation. Expressions of these factors are regulated by some compounds such as fatty acids or some steroid hormones （insulin） which is stimulated by the nutritional level. Furthermore, these factors are related to some metabolic diseases including type II diabetes and obesity, Lots of researches have focused on relationships between the factors and the genetic diseases. Different functions of factors on inducing the adipocyte differentiation are other hot spots according to previous studies. This paper summarized these studies and gave a limpid description of structures and functions of these genes.展开更多
Aronia melamocarpa (AM) is a rich source of anthocyanins, which are known to help prevent obesity. The cyanidine-3-O-galactoside enriched AM extract (AM-Ex) containing more cyanidine-3-O-galactoside than conventional ...Aronia melamocarpa (AM) is a rich source of anthocyanins, which are known to help prevent obesity. The cyanidine-3-O-galactoside enriched AM extract (AM-Ex) containing more cyanidine-3-O-galactoside than conventional AM extract was recently developed. The objective of this study was to examine the effect of AM-Ex on adipogenesis and its action mechanisms in vitro using 3T3-L1 adipocytes. To examine the anti-obesity effect of AM-Ex, 3T3-L1 cells were induced adipocyte differentiation and incubated with various concentration of AM-Ex. Lipid accumulation, cellular triglyceride content, mRNA expression of transcription factors and adipogenic genes were analyzed. Treatment with 100 - 400 μg/mL of AM-Ex resulted in a dose-dependent decrease in adipocyte differentiation and triglyceride accumulation. mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein α, sterol regulatory element-binding protein 1 were decreased. The level of gene expression of adipogenesis and lipogenesis-related genes, such as adipocyte protein 2, lipoprotein lipase, acetyl-CoA carboxylase, ATP-citrate lyase and fatty acid synthase were decreased. These results suggest that AM-Ex alleviated risk factors related to obesity by modulating multiple pathways associated with adipogenesis.展开更多
Background:N6-methyladenosine(m^(6)A)is an abundant post-transcriptional RNA modification that affects various biological processes.The fat mass and obesity-associated(FTO)protein,a demethylase encoded by the FTO gene...Background:N6-methyladenosine(m^(6)A)is an abundant post-transcriptional RNA modification that affects various biological processes.The fat mass and obesity-associated(FTO)protein,a demethylase encoded by the FTO gene,has been found to regulate adipocyte development in an m^(6)A-dependent manner in multiple species.However,the effects of the m^(6)A methylation and FTO demethylation functions on chicken adipogenesis remain unclear.This study aims to explore the association between m^(6)A modification and chicken adipogenesis and the underlying mechanism by which FTO affects chicken preadipocyte development.Results:The association between m^(6)A modification and chicken lipogenesis was assessed by treating chicken pread-ipocytes with different doses of methyl donor betaine and methylation inhibitor cycloleucine.The results showed that betaine significantly increased methylation levels and inhibited lipogenesis,and the inverse effect was found in preadipocytes after cycloleucine treatment.Overexpression of FTO significantly inhibited m^(6)A levels and promoted proliferation and differentiation of chicken preadipocytes.Silencing FTO showed opposite results.Mechanistically,FTO overexpression increased the expression of catenin beta 1(CTNNB1)by improving RNA stability in an m^(6)A-dependent manner,and we proved that FTO could directly target CTNNB1.Furthermore,CTNNB1 may be a positive regulator of adipogenesis in chicken preadipocytes.Conclusions:m^(6)A methylation of RNA was negatively associated with adipogenesis of chicken preadipocytes.FTO could regulate CTNNB1 expression in a demethylation manner to promote lipogenesis.展开更多
OBJECTIVE： Traditional Korean Chungtaejeon （CTJ） tea is a type of fermented tea, which has received increasing attention in recent years because of its purported health benefits. The present study was designed to i...OBJECTIVE： Traditional Korean Chungtaejeon （CTJ） tea is a type of fermented tea, which has received increasing attention in recent years because of its purported health benefits. The present study was designed to investigate the effect and mechanism of CTJ tea extract on body weight gain using C57BL/6J-Lep ob/ob mice and 3T3-L1 adipocytes, respectively. METHODS： The effects of CTJ on cell viability, lipid accumulation, and expression of protein and mRNA were measured in 3T3-L1 adipocytes by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, oil red O staining, Western blotting, and reverse transcriptase-polymerase chain reaction analyses. C57BL6J-Lep ob/ob mice were administered with CTJ （200 or 400 mg/kg body weight） for ten weeks. Then, body weight, food intake, total cholesterol, and triglyceride were measured in ob/ob mice. RESULTS： CTJ tea extract treated at 250 wg/mL （CTJ250） significantly suppressed lipid accumulation in the differentiated 3T3-L1 adipocytes. Likewise, CTJ250 significantly decreased the protein expression of peroxisome proliferator-activated receptor Y （PPARy）, CCJ^u~,T/enhancer-binding protein a, and adipocyte lipid- binding protein, and regulated the mRNA expression of PPART, sterol regulatory element-binding protein- lc gene, fatty acid synthase, adipocyte lipid-binding protein, hormone-sensitive lipase, carnitine palmitoyl transferase 1, cluster of differentiation 36, and acetyl-CoA carboxylase in the differentiated 3T3-L1 adipocytes. Mice administered with CTJ showed dose-dependent decrease in body weight gain, starting from week 4 of the experiment. CTJ tea extract administered at 400 mg/kg body weight significantly decreased fat mass, food efficacy ratio, and levels of plasma triglyceride and total cholesterol. CONCLUSION： CTJ attenuated weight gain in ob/ob mice and regulated the activity of the molecules involved in adipogenesis and lipolysis in 3T3-L1 adipocytes. CTJ is a potentially valuable herbal therapy for the prevention of obesity and/or obesity-related disorders.展开更多
Adamantane polycyclic polyprenylated acylphloroglucinols(PPAPs)with caged architecture,a special class of hybrid natural products,is specifically rich in the plant family Guttiferae,especially Hypericum or Garcinia ge...Adamantane polycyclic polyprenylated acylphloroglucinols(PPAPs)with caged architecture,a special class of hybrid natural products,is specifically rich in the plant family Guttiferae,especially Hypericum or Garcinia genus.Hypersampsone P is one of Adamantane PPAPs compounds extracted from Hypericum subsessile.Here we have chosen,screened ten PPAPs and identified one of them showed an activity in inhibiting of adipocytes differentiation.Particularly,the compound,hypersamp-sone P,blunted the adipocyte differentiation dose-dependently.Moreover,hypersampsone P down-regulated the expressions of several key regulators for adipogenesis,including PPARγand FABP4.The treatment of cells at the early stage of adipo-genesis by hypersampsone P induced the greatest blunting of adipocyte differentiation and the effect might be involved in the LKB1-AMPK signaling pathway.展开更多
Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life....Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life.Several studies showed that imbalance between the osteogenesis and adipogenesis of bone marrow mesenchymal stem cells(BMSCs)took part in the development of osteoporosis.In previous study,we found MIR22HG regulated the osteogenesis of human BMSCs positively.In this study,we found that MIR22HG was decreased during the adipogenesis of human BMSCs and exerted negative effects on adipogenesis with the involvement of Wnt/β-catenin signaling pathway both in vitro and in vivo.Nitazoxanide could inhibit Wnt signaling and relieve MIR22HG’s suppression on adipogenesis.These findings indicated that MIR22HG had great potential in clinical application for osteoporosis treatment and prevention.展开更多
Obesity is crucially involved in many metabolic diseases,such as type 2 diabetes,cardiovascular disease and cancer.Regulating the number or size of adipocytes has been suggested to be a potential treatment for obesity...Obesity is crucially involved in many metabolic diseases,such as type 2 diabetes,cardiovascular disease and cancer.Regulating the number or size of adipocytes has been suggested to be a potential treatment for obesity.In this study,we investigated the effect of pyrocincholic acid 3β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside(PAQG),a 27-nor-oleanolic acid saponin extracted from Metadina trichotoma,on adipogenesis and lipid metabolism in 3T3-L1 adipocytes.The 3T3-L1 pre-adipocytes were incubated with vehicle or PAQG for 6 days in differentiation process.PAQG significantly reduced the adipogenesis,adiponectin secretion and the expression level of key transcription factors related to adipogenesis,such as PPARc,C/EBPb,C/EBPa,and FABP4.Moreover,PAQG increased the levels of FFA and glycerol in medium and reduced TG level in mature adipocytes.Interestingly,PAQG not only promoted the activation of AMPK and genes involved in fatty oxidation including PDK4 and CPT1a,but also inhibited those genes involved in fatty acid biosynthesis,such as SREBP1c,FAS,ACCa and SCD1.In conclusion,PAQG inhibits the differentiation and regulates lipid metabolism of 3T3-L1 cells via AMPK pathway,suggesting that PAQG may be a novel and promising natural product for the treatment of obesity and hyperlipidemia.展开更多
Citrullus colocynthis, a member of the Cucurbitaceae family, is widely distributed in North Africa. The fruits are recognized for their wide range of medicinal uses and promising pharmaceutical potential. The present ...Citrullus colocynthis, a member of the Cucurbitaceae family, is widely distributed in North Africa. The fruits are recognized for their wide range of medicinal uses and promising pharmaceutical potential. The present study aimed to investigate the anti-obesity effect of the ethanol extract of colocynth flesh (FCEE) in 3T3-L1 cells following treatment at different doses. The viability of 3T3-L1 preadipocytes was analyzed via MTT assay and triglycerides were stained with Oil red O to assess lipid accumulation. Additionally, adipogenesis-related gene expression was quantified via qRT-PCR. FCEE (0 - 150 μg/mL) dose-dependently suppressed intracellular triglyceride accumulation during the adipogenesis by 23% and 66% at 100 and 150 μg/mL, respectively, but did not affect cell viability. Analysis of the time-dependence of the effect of FCEE demonstrated that the greatest anti-adipogenic activity was observed during the early stages of differentiation. FCEE also decreased GPDH activity in a dose-dependent manner, with 98% decrease observed at 150 μg/mL. In addition, at same range of FCEE concentrations, the main transcription factors, including CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator activated receptor γ (PPARγ), and sterol regulatory element-binding protein 1c (SREBP-1c), were downregulated by 90%, 89%, and 89%, respectively at 150 μg/mL. As these are the master regulators of adipogenesis. The inhibition of their downstream target genes was also observed. Colocynth may be useful in the treatment of obesity owing to its powerful effects on fat, which result in changes to adipocyte differentiation and fat mobilization.展开更多
基金supports from Odense University Hospital PhD fellowship(2014)the NovoNordisk Foundations(NNF15OC0016284,NNF19OC0057449)+2 种基金the Innovation Foundation of Denmark(5166-00002B)National Natural Science Foundation of China(No.32060155,82260284)Guangxi Medical and Health Key Discipline Construction Project.
文摘An increasing number of studies have characterized the bone as an endocrine organ,and that bone secreted factors may not only regulate local bone remodeling,but also other tissues and whole-body metabolic functions.The precise nature of these regulatory factors and their roles at bridging the bone,bone marrow adipose tissue,extramedullary body fat and whole-body energy homeostasis are being explored.In this study,we report that KIAA1199,a secreted factor produced from bone and bone marrow,previously described as an inhibitor of bone formation,also plays a role at promoting adipogenesis.KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue,subcutaneous and visceral fat tissue mass,blood cholesterol,triglycerides,free fatty acids and glycerol,as well as improved insulin sensitivity in skeletal muscle,liver and fat.Moreover,these mice are protected from the detrimental effects of high-fat diet feeding,with decreased obesity,lower blood glucose and glucose tolerance,as well as decreased adipose tissue inflammation,insulin resistance and hepatic steatosis.In human studies,plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol,triglycerides,free fatty acids,glycerol,fasting glucose and HOMA-IR.Mechanistically,KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT/ERK signaling.These findings provide evidence for the role of bone secreted factors on coupling bone,fat and whole-body energy homeostasis.
基金supported by the Joint Fund for Regional Innovation and Development of the National Natural Science Foundation of China(U23A20226)Science and Technology Planning Project of Inner Mongolia Autonomous Region(2023KYPT0014)。
文摘Adipose-derived mesenchymal stem cells(ADSCs)represent a readily accessible and important source of mesenchymal stem cells(MSCs)capable of multilineage differentiation.The Hippo signaling pathway effector YAP has emerged as a pivotal regulator of stem cell fate,yet the specific molecular mechanism by which it modulates lipogenic differentiation of ADSCs has not been clearly defined.In this study,goat ADSCs(gADSCs)isolated from Albas goats in Inner Mongolia were used to investigate the role of YAP1 in adipogenic differentiation.Overexpression of YAP1 significantly promoted the differentiation of ADSCs into adipocytes,an effect accompanied by up-regulation of LATS2 and activation of the negative feedback loop of the Hippo signaling pathway.Elevated LATS2 expression induced YAP phosphorylation,leading to reduced nuclear levels of YAP and TAZ and their subsequent accumulation in the cytoplasm.YAP1 overexpression up-regulated LATS2 expression,which,in turn,enhanced the adipogenic differentiation of ADSCs.This pro-adipogenic effect of YAP1 was dependent on LATS2 kinase activity.These findings indicate that overexpression of YAP1 promotes ADSC adipogenesis by inducing LATS2 expression and activating the Hippo pathway negative feedback loop.Elucidating the molecular role of YAP in ADSC lipogenic differentiation holds great significance for regulating stem cell fate,treating metabolic disorders,and promoting hair follicle growth.
基金financially supported by the National Key Research and Development Program of China(Grant No.2023YFD1301300)。
文摘Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear.Lysine 2-hydroxyisobutyrylation(Khib),is a novel protein post-translational modification(PTM),which play an important role in transcription,energy metabolism and metastasis of cancer cells,but its role in adipogenesis and fat accumulation has not been shown.Results In this study,we first analyzed the modification levels of acetylation(Kac),Khib,crotonylation(Kcr)and succinylation(Ksu)of fibro-adipogenic progenitors(FAPs),myogenic precursors(Myo)and mesenchymal stem cells(MSCs)with varied differentiation potential,and found that only Khib modification in FAPs was significantly higher than that in MSCs.Consistently,in parallel with its regulatory enzymes lysine acetyltransferase 5(KAT5)and histone deacetylase 2(HDAC2)protein levels,the Khib levels increased quadratically(P<0.01)during adipogenic differentiation of FAPs.KAT5 knockdown in FAPs inhibited adipogenic differentiation,while HDAC2 knockdown enhanced adipogenic differentiation.We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs(Laiwu pigs)and lean-type pigs(Duroc pigs),respectively.Accordingly,the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese-and lean-type pigs.Conclusions From the perspective of protein translational modification,we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs,and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.
基金supported by the Key Research and Development Program of Hunan Province(2023SK2038)the Natural Science Foundation of Hunan Province(2024JJ8121),China。
文摘Objective:Pelvic organ prolapse(POP)is a common condition in postmenopausal women,with an increasing prevalence due to aging.Some women experience POP recurrence after surgical treatment,significantly affecting their physical and mental health.The uterosacral ligament is a critical pelvic support structure.This study aims to investigate the molecular pathological changes in the uterosacral ligament of postmenopausal women with recurrent POP using transcriptomic analysis.Methods:Transcriptomic data of uterosacral ligament tissues were obtained from the public dataset GSE28660,which includes samples from 4 postmenopausal women with recurrent POP,4 with primary POP,and 4 without POP.Differentially expressed genes(DEGs)were identified between recurrent POP and both primary and non-POP groups.Further analysis included intersection analysis of DEGs,gene ontology enrichment,protein protein interaction(PPI)network construction,gene set enrichment analysis(GSEA),single-sample GSEA,and xCell immune cell infiltration analysis to explore molecular pathological changes in recurrent POP.Additionally,histological and molecular differences in the uterosacral ligament were compared between simulated vaginal delivery(SVD)rat models with and without ovariectomy.Results:Compared with primary POP and non-POP groups,recurrent POP exhibited activation of adipogenesis and inflammation-related pathways,while pathways related to muscle proliferation and contraction were downregulated in the uterosacral ligament.Nine key DEGs(ADIPOQ,FABP4,IL-6,LIPE,LPL,PCK1,PLIN1,PPARG,and CD36)were identified,with most enriched in the peroxisome proliferator-activated receptor(PPAR)signaling pathway.These genes were significantly correlated with lipid accumulation,monocyte infiltration,and neutrophil infiltration in the uterosacral ligament.Urodynamic testing revealed that the bladder leak point pressure was significantly higher in ovariectomized SVD rats,both of which had higher values than the sham group.Masson staining showed pronounced adipogenesis in the uterosacral ligament of ovariectomized SVD rats,along with reduced collagen and muscle fibers compared to the sham and non ovariectomized SVD groups.Furthermore,real-time RT-PCR confirmed significantly elevated expression of key DEGs,including ADIPOQ,IL-6,PCK1,and PLIN1,in the uterosacral ligaments of ovariectomized SVD rats.Conclusion:Adipogenesis and inflammation in the uterosacral ligament may contribute to its reduced supportive function,potentially leading to recurrence POP in postmenopausal women.
基金Beijing Natural Science Foundation(Grant No.2171001)the National Natural Science Foundation of China(Grant No.31571403)the National High-tech R&D Program of China(Grant No.2014AA021103)
文摘Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential role. To explore the function of Dnmt1, its expression was first profiled during the course of adipocyte differentiation of 3T3-L1 cells. The results revealed a dynamic regulation of its expression at the initiation stage. Knockdown of Dnmt1 compromised the differentiation process and decreased lipid production within the cells. To the aspect of epigenetic regulation, promoter methylation of Cdkn1a was significantly increased at the initiation stage of the differentiation, accompanied by decreased Cdkn1a expression. Furthermore, knockdown of Dnmt1 led to an increased Cdkn1a expression, indicating that Dnmt1 inhibits Cdkn1a expression by promoter methylation. Furthermore, we found that knockdown of Cdkn1a up-regulated the expression of PPARγ and resulted in enhanced adipocyte differentiation. In summary, our results demonstrated that Dnmt1 regulated the process of adipogenesis by methylation of Cdkn1a promoter, suggesting that Cdkn1a played a fundamental role in the prevention of adipocyte hyperplasia.
文摘Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation of 3T3-L1 cells requires two processes： the licensing of an adipogenesis gene-expression program within a particular growth-arrest stage, i.e., the contact-inhibition stage, and then the execution of this program in a cell-cycle-independent manner, by which the licensed progenitors are differentiated into adipocytes in the presence of inducing factors. Our results showed that differentiation licensing of 3T3-L1 cells during the contact-inhibition stage involved epigenetic modifications such as DNA methylation and histone modifications, whereas disturbing these epigenetic modifications by DNA methylation inhibitors or RNAi during the contact-inhibition stage significantly reduced adipogenesis efficiency. More importantly, when these licensed 3T3-L1 cells were re-cultured under non-differentiating conditions or treated only with insulin, this adipogenesis commitment could be maintained from one cell generation to the next, whereby the licensed program could be activated in a cell-cycle-independent manner once these cells were subjected to adipo- genesis-inducing conditions. This result suggests that differentiation licensing and differentiation execution can be uncoupled and disparately linked to cell proliferation. Our findings deliver a new concept that cell-fate decision can be subdivided into at least two stages, licensing and execution, which might have different regulatory relationships with cell proliferation. In addition, this new concept may provide a clue for developing new strategies against obesity.
文摘SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-binding protein a （C/EBPa） during adipocyte differentiation. C/EBPa, but not C/EBPap30, activated SIRT1 promoter in both HeLa cells and 3T3-L1 preadipocytes. Furthermore, C/EBPa upregulated SIRT1 mRNA and protein levels in HeLa cells and increased SIRT1 expression in a p53-independent manner in Soas2 cells. In preadipocytes, ectopic expression of C/EBPa upregulated SIRT1 protein level and knockdown of C/EBPa led to the decrease of SIRTI pro- tein level. Moreover, by promoter deletion analysis, gel shift assay and chromatin immunoprecipitation, we found that C/EBPa bound to the SIRT1 promoter at a consensus C/EBPα binding site. These data demonstrate that C/ EBPα regulates SIRT1 expression during adipogenesis by directly binding to the SIRT1 promoter.
基金supported by the National Key Research and Development Program of China(2021YFD1200803)Sanya Yazhou Bay Science and Technology City Administration(SYND-2022-28)China Agriculture Research System of MOF and MARA(CARS-40).
文摘Background:Excessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality,feed utilization,and reproduction.Abdominal fat deposition depends on the proliferation of preadipocytes and their maturation into adipocytes,which involves a cascade of regulatory molecules.Accumulating evidence has shown that microRNAs(miRNAs)serve as post-transcriptional regulators of adipogenic differentiation in mammals.However,the miRNA-mediated molecular mechanisms underlying abdominal fat deposition in chickens are still poorly understood.This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken abdominal adipogenesis.Results:We established a chicken model of abdominal adipocyte differentiation and analyzed miRNA and mRNA expression in abdominal adipocytes at different stages of differentiation(0,12,48,72,and 120 h).A total of 217 differentially expressed miRNAs(DE-miRNAs)and 3520 differentially expressed genes were identified.Target prediction of DE-miRNAs and functional enrichment analysis revealed that the differentially expressed targets were significantly enriched in lipid metabolism-related signaling pathways,including the PPAR signaling and MAPK signaling pathways.A candidate miRNA,gga-miR-106-5p,exhibited decreased expression during the proliferation and differentiation of abdominal preadipocytes and was downregulated in the abdominal adipose tissues of fat chickens compared to that of lean chickens.gga-miR-106-5p was found to inhibit the proliferation and adipogenic differentiation of chicken abdominal preadipocytes.A dual-luciferase reporter assay suggested that the KLF15 gene,which encodes a transcriptional factor,is a direct target of gga-miR-106-5p.gga-miR-106-5p suppressed the posttranscriptional activity of KLF15,which is an activator of abdominal preadipocyte proliferation and differentiation,as determined with gain-and loss-of-function experiments.Conclusions:gga-miR-106-5p functions as an inhibitor of abdominal adipogenesis by targeting the KLF15 gene in chickens.These findings not only improve our understanding of the specific functions of miRNAs in avian adipogenesis but also provide potential targets for the genetic improvement of excessive abdominal fat deposition in poultry.
基金supported by the Strategic Priority Research Program of CAS(No.XDB14040201)National Natural Science Foundation of China(Nos.21806179,21621064 and21672255)
文摘Methyl tert-butyl ether (MTBE),as a widely used gasoline additive,is suspected of being environmentally toxic.MTBE accumulates mainly in adipose tissue,but its effect on obesity or obesity-related metabolic disorders has not been well understood yet.Therefore,we examined the effect of MTBE on the adipose function and the related metabolic processes with both 3T3-L1 cell line and C57BL/6J mice model.We found that exposure to MTBE at the environmental relevant concentration (100 μmol/L) could significantly induce differentiation of preadipocyte and disturb insulin-stimulated glucose uptake of mature adipocyte.The in vivo observation in male mice showed a positive correlation of visceral white adipose tissue (vWAT) expansion and cell size increase with MTBE treatment in 14 weeks.Glucose tolerance and insulin sensitivity tests demonstrated that MTBE at 1000 μg/(kg·day) disturbed the systemic glucose metabolism in a gender-specific manner,which might be partly attributed to the alterations of gut microbiota community at genus level with respect to Akkermansia,Clostridium XIVb,and Megamonas.In summary,our study characterized the effect of MTBE on adipose tissue function and glucose homeostasis in vitro and in vivo,and revealed that systemic disorders of the glucose metabolism might be modulated by the related gut microbiota.
基金Project supported by the National Natural Science Foundation of China (Nos. 31071027 and 30870926)the National Key Technology R&D Program of China (No. 2008BAC39B05)the Fund from Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education and Beijing Key Laboratory of Engineered Drug and Bio-technology,Beijing Normal University,China
文摘It is generally agreed that adipocytes originate from mesenchymal stem cells in what can be divided into two processes:determination and differentiation.In the past decade,many factors associated with epigenetic signals have been proved to be pivotal for the appropriate timing of adipogenesis progression.A large number of coregulators at critical gene promoters set up specific patterns of DNA methylation,histone acetylation and methylation,and nucleosome rearrangement,that act as an epigenetic code to modulate the correct progress of adipocyte differentiation and adipogenesis during adipogenesis.In this review,we focus on the functions and roles of epigenetic processes in preadipocyte differentiation and adipogenesis.
基金funded by the National Natural Science Foundation of China (31972994)Key Research and Development Program of Ningxia Province (2019BEF02004)+1 种基金National Beef and Yak Industrial Technology System (CARS-37)National Key Research and Development Program of China (2018YFD0501700)。
文摘Background Long non-coding RNAs(lncRNAs)regulate numerous biological processes,including adipogenesis.Research on adipogenesis will assist in the treatment of human metabolic diseases and improve meat quality in livestock,such as the content of intramuscular fat(IMF).However,the significance of lncRNAs in intramuscular adipogenesis remains unclear.This research aimed to reveal the lncRNAs transcriptomic profiles in the process of bovine intramuscular adipogenesis and to identify the lncRNAs involved in the adipogenesis of bovine intramuscular adipocytes.Results In this research,a landscape of lncRNAs was identified with RNA-seq in bovine intramuscular adipocytes at four adipogenesis stages(0 d,3 d,6 d,and 9 d after differentiation).A total of 7035 lncRNAs were detected,including 3396 novel lncRNAs.Based on the results of differential analysis,co-expression analysis,and functional prediction,we focused on the bovine intramuscular adipogenesis-associated long non-coding RNA(BIANCR),a novel lncRNA that may have an important regulatory function.The knockdown of BIANCR inhibited proliferation and promoted apoptosis of intramuscular preadipocytes.Moreover,BIANCR knockdown inhibited intramuscular adipogenesis by regulating the ERK1/2 signaling pathway.Conclusion This study obtained the landscape of lncRNAs during adipogenesis in bovine intramuscular adipocytes.BIANCR plays a crucial role in adipogenesis through the ERK1/2 signaling pathway.The results are noteworthy for improving beef meat quality,molecular breeding,and metabolic disease research.
文摘Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and apoptosis,in an MMP-independent manner.This study aimed to examine the role of TIMP-1 in adipogenesis of adipose-derived stem cells(ASCs)and the underlying mechanism.We knocked down the TIMP-1 gene in ASCs through lentiviral vectors encoding TIMP-1 small interfering RNA(siRNA),and then found that the knockdown of TIMP-1 in ASCs promoted the adipogenic differentiation of stem cells and inhibited the Wnt/β-catenin signaling pathway in ASCs.We also noted that mutant TIMP-1 without the inhibitory activity on MMPs promoted the activation of Wnt/β-catenin pathway as well as the recombinant wild type TIMP-1 did,which indicated that the effect of TIMP-1 on Wnt/β-catenin pathway was MMPindependent.Our study suggested that TIMP-1 negatively regulated the adipogenesis of ASCs via the Wnt/β-catenin signaling pathway in an MMP-independent manner.
基金Supported by National Natural Science Foundation Key Project of China(30430510)Natural Science Foundation Key Project of Heilongjiang Province(ZJN0604-01)National 973 Project of China(2006CB102105)
文摘Lipid metabolism and adipocyte differentiation are reglulated by networking of transcription factors. It is generally known that three factors, peroxisome proliferator-activated receptor y （PPARγ）, CCAAT/element-binding protein a （C/EBPa） and sterol regulatory element binding protein-1 （SREBP1）, play fundamental roles in metabolic pathways. And they are also important in adipocyte differentiation. Expressions of these factors are regulated by some compounds such as fatty acids or some steroid hormones （insulin） which is stimulated by the nutritional level. Furthermore, these factors are related to some metabolic diseases including type II diabetes and obesity, Lots of researches have focused on relationships between the factors and the genetic diseases. Different functions of factors on inducing the adipocyte differentiation are other hot spots according to previous studies. This paper summarized these studies and gave a limpid description of structures and functions of these genes.
文摘Aronia melamocarpa (AM) is a rich source of anthocyanins, which are known to help prevent obesity. The cyanidine-3-O-galactoside enriched AM extract (AM-Ex) containing more cyanidine-3-O-galactoside than conventional AM extract was recently developed. The objective of this study was to examine the effect of AM-Ex on adipogenesis and its action mechanisms in vitro using 3T3-L1 adipocytes. To examine the anti-obesity effect of AM-Ex, 3T3-L1 cells were induced adipocyte differentiation and incubated with various concentration of AM-Ex. Lipid accumulation, cellular triglyceride content, mRNA expression of transcription factors and adipogenic genes were analyzed. Treatment with 100 - 400 μg/mL of AM-Ex resulted in a dose-dependent decrease in adipocyte differentiation and triglyceride accumulation. mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein α, sterol regulatory element-binding protein 1 were decreased. The level of gene expression of adipogenesis and lipogenesis-related genes, such as adipocyte protein 2, lipoprotein lipase, acetyl-CoA carboxylase, ATP-citrate lyase and fatty acid synthase were decreased. These results suggest that AM-Ex alleviated risk factors related to obesity by modulating multiple pathways associated with adipogenesis.
基金funded by the Natural Scientific Foundation of China(U1901206)Local Innovative and Research Teams Project of Guangdong Province(2019BT02N630)+4 种基金the Science and Technology Program of Guangdong province,China(2020B1212060060)the Science and Technology Program of Guangzhou,China(202103000084)the Construction Project of Modern Agricultural Science and Technology Innovation Alliance in Guangdong Province(2021KJ128)National Key R&D Program of China(2021YFD1300100)China Agriculture Research System(CARS-41-G03).
文摘Background:N6-methyladenosine(m^(6)A)is an abundant post-transcriptional RNA modification that affects various biological processes.The fat mass and obesity-associated(FTO)protein,a demethylase encoded by the FTO gene,has been found to regulate adipocyte development in an m^(6)A-dependent manner in multiple species.However,the effects of the m^(6)A methylation and FTO demethylation functions on chicken adipogenesis remain unclear.This study aims to explore the association between m^(6)A modification and chicken adipogenesis and the underlying mechanism by which FTO affects chicken preadipocyte development.Results:The association between m^(6)A modification and chicken lipogenesis was assessed by treating chicken pread-ipocytes with different doses of methyl donor betaine and methylation inhibitor cycloleucine.The results showed that betaine significantly increased methylation levels and inhibited lipogenesis,and the inverse effect was found in preadipocytes after cycloleucine treatment.Overexpression of FTO significantly inhibited m^(6)A levels and promoted proliferation and differentiation of chicken preadipocytes.Silencing FTO showed opposite results.Mechanistically,FTO overexpression increased the expression of catenin beta 1(CTNNB1)by improving RNA stability in an m^(6)A-dependent manner,and we proved that FTO could directly target CTNNB1.Furthermore,CTNNB1 may be a positive regulator of adipogenesis in chicken preadipocytes.Conclusions:m^(6)A methylation of RNA was negatively associated with adipogenesis of chicken preadipocytes.FTO could regulate CTNNB1 expression in a demethylation manner to promote lipogenesis.
基金supported by the Technology Development Program for Agriculture and Forestry, Ministry for Agriculture, Forestiy and Fisheries, Republic of Korea
文摘OBJECTIVE： Traditional Korean Chungtaejeon （CTJ） tea is a type of fermented tea, which has received increasing attention in recent years because of its purported health benefits. The present study was designed to investigate the effect and mechanism of CTJ tea extract on body weight gain using C57BL/6J-Lep ob/ob mice and 3T3-L1 adipocytes, respectively. METHODS： The effects of CTJ on cell viability, lipid accumulation, and expression of protein and mRNA were measured in 3T3-L1 adipocytes by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, oil red O staining, Western blotting, and reverse transcriptase-polymerase chain reaction analyses. C57BL6J-Lep ob/ob mice were administered with CTJ （200 or 400 mg/kg body weight） for ten weeks. Then, body weight, food intake, total cholesterol, and triglyceride were measured in ob/ob mice. RESULTS： CTJ tea extract treated at 250 wg/mL （CTJ250） significantly suppressed lipid accumulation in the differentiated 3T3-L1 adipocytes. Likewise, CTJ250 significantly decreased the protein expression of peroxisome proliferator-activated receptor Y （PPARy）, CCJ^u~,T/enhancer-binding protein a, and adipocyte lipid- binding protein, and regulated the mRNA expression of PPART, sterol regulatory element-binding protein- lc gene, fatty acid synthase, adipocyte lipid-binding protein, hormone-sensitive lipase, carnitine palmitoyl transferase 1, cluster of differentiation 36, and acetyl-CoA carboxylase in the differentiated 3T3-L1 adipocytes. Mice administered with CTJ showed dose-dependent decrease in body weight gain, starting from week 4 of the experiment. CTJ tea extract administered at 400 mg/kg body weight significantly decreased fat mass, food efficacy ratio, and levels of plasma triglyceride and total cholesterol. CONCLUSION： CTJ attenuated weight gain in ob/ob mice and regulated the activity of the molecules involved in adipogenesis and lipolysis in 3T3-L1 adipocytes. CTJ is a potentially valuable herbal therapy for the prevention of obesity and/or obesity-related disorders.
基金supported by Yunnan Provincial Science and Technology Department,China(2017FA044)Chongqing Municipal Natural Science Foundation(cstc2018jcyjAX0388).
文摘Adamantane polycyclic polyprenylated acylphloroglucinols(PPAPs)with caged architecture,a special class of hybrid natural products,is specifically rich in the plant family Guttiferae,especially Hypericum or Garcinia genus.Hypersampsone P is one of Adamantane PPAPs compounds extracted from Hypericum subsessile.Here we have chosen,screened ten PPAPs and identified one of them showed an activity in inhibiting of adipocytes differentiation.Particularly,the compound,hypersamp-sone P,blunted the adipocyte differentiation dose-dependently.Moreover,hypersampsone P down-regulated the expressions of several key regulators for adipogenesis,including PPARγand FABP4.The treatment of cells at the early stage of adipo-genesis by hypersampsone P induced the greatest blunting of adipocyte differentiation and the effect might be involved in the LKB1-AMPK signaling pathway.
基金This study was financially supported by grants from the National Natural Science Foundation of China(82071119,82071142,81700938,81772876,81800942).
文摘Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life.Several studies showed that imbalance between the osteogenesis and adipogenesis of bone marrow mesenchymal stem cells(BMSCs)took part in the development of osteoporosis.In previous study,we found MIR22HG regulated the osteogenesis of human BMSCs positively.In this study,we found that MIR22HG was decreased during the adipogenesis of human BMSCs and exerted negative effects on adipogenesis with the involvement of Wnt/β-catenin signaling pathway both in vitro and in vivo.Nitazoxanide could inhibit Wnt signaling and relieve MIR22HG’s suppression on adipogenesis.These findings indicated that MIR22HG had great potential in clinical application for osteoporosis treatment and prevention.
文摘Obesity is crucially involved in many metabolic diseases,such as type 2 diabetes,cardiovascular disease and cancer.Regulating the number or size of adipocytes has been suggested to be a potential treatment for obesity.In this study,we investigated the effect of pyrocincholic acid 3β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside(PAQG),a 27-nor-oleanolic acid saponin extracted from Metadina trichotoma,on adipogenesis and lipid metabolism in 3T3-L1 adipocytes.The 3T3-L1 pre-adipocytes were incubated with vehicle or PAQG for 6 days in differentiation process.PAQG significantly reduced the adipogenesis,adiponectin secretion and the expression level of key transcription factors related to adipogenesis,such as PPARc,C/EBPb,C/EBPa,and FABP4.Moreover,PAQG increased the levels of FFA and glycerol in medium and reduced TG level in mature adipocytes.Interestingly,PAQG not only promoted the activation of AMPK and genes involved in fatty oxidation including PDK4 and CPT1a,but also inhibited those genes involved in fatty acid biosynthesis,such as SREBP1c,FAS,ACCa and SCD1.In conclusion,PAQG inhibits the differentiation and regulates lipid metabolism of 3T3-L1 cells via AMPK pathway,suggesting that PAQG may be a novel and promising natural product for the treatment of obesity and hyperlipidemia.
文摘Citrullus colocynthis, a member of the Cucurbitaceae family, is widely distributed in North Africa. The fruits are recognized for their wide range of medicinal uses and promising pharmaceutical potential. The present study aimed to investigate the anti-obesity effect of the ethanol extract of colocynth flesh (FCEE) in 3T3-L1 cells following treatment at different doses. The viability of 3T3-L1 preadipocytes was analyzed via MTT assay and triglycerides were stained with Oil red O to assess lipid accumulation. Additionally, adipogenesis-related gene expression was quantified via qRT-PCR. FCEE (0 - 150 μg/mL) dose-dependently suppressed intracellular triglyceride accumulation during the adipogenesis by 23% and 66% at 100 and 150 μg/mL, respectively, but did not affect cell viability. Analysis of the time-dependence of the effect of FCEE demonstrated that the greatest anti-adipogenic activity was observed during the early stages of differentiation. FCEE also decreased GPDH activity in a dose-dependent manner, with 98% decrease observed at 150 μg/mL. In addition, at same range of FCEE concentrations, the main transcription factors, including CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator activated receptor γ (PPARγ), and sterol regulatory element-binding protein 1c (SREBP-1c), were downregulated by 90%, 89%, and 89%, respectively at 150 μg/mL. As these are the master regulators of adipogenesis. The inhibition of their downstream target genes was also observed. Colocynth may be useful in the treatment of obesity owing to its powerful effects on fat, which result in changes to adipocyte differentiation and fat mobilization.
