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Intramuscular adipose tissue (IMAT) formation is observed in some pathological conditions such as Duchenne muscular dystrophy (DMD) and sarcopenia. Several studies have suggested that IMAT formation is not only negatively correlated with skeletal muscle mass but also causes decreased muscle contraction in sarcopenia. In the present study, we examined w hether adipocytes affect myogenesis. For this purpose, skeletal muscle progenitor cells were transfected with siRNA of PPARγ (siPPARγ) in an attempt to inhibit adipogenesis. Myosin heavy chain (MHC)-positive myotube formation was promoted in cells transfected with siPPARγ compared to that of cells transfected with control siRNA. To determine whether direct cell-to-cell contact between adipocytes and myoblasts is a prerequisite for adipocytes to affect myogenesis, skeletal muscle progenitor cells were cocultured with pre- or mature adipocytes in a Transwell coculture system. MHC-positive myotube formation was inhibited when skeletal muscle progenitor cells were cocultured with mature adipocytes, but was promoted when they were cocultured with preadipocytes. Similar effects were observed when pre- or mature adipocyte-conditioned medium was used. These results indicate that preadipocytes play an important role in maintaining skeletal muscle mass by promoting myogenesis; once differentiated, the resulting mature adipocytes negatively affect myogenesis, leading to the muscle deterioration observed in skeletal muscle pathologies.  相似文献   
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干预GPR1通路对实验性小鼠脂肪累积的影响   总被引:1,自引:0,他引:1  
一直以来,肥胖是令人担忧和烦恼的健康问题,可导致包括2型糖尿病在内的代谢综合征发生.与肥胖相关疾病的发病机制是多因子影响的结果,但是,越来越多的证据表明,脂肪组织分泌的细胞因子(脂联素、瘦素、TNF-α等)的改变,以及局部的炎症反应对于这些疾病的发生具有重要作用.Chemerin(也被称为他扎罗汀诱导基因2或者视黄酸受体反应子2),是近年来发现的一种脂肪细胞因子,是G蛋白偶联受体1(GPR1)的配体,在调节代谢、先天免疫等方面具有重要的作用.为了研究Chemerin及其受体GPR1对小鼠脂肪累积的影响,本课题组通过高脂饲料喂养,成功建立小鼠肥胖模型,利用si RNA干扰技术沉默小鼠和分化前3T3-L1细胞中Chemerin或GPR1基因的表达发现:a.Chemerin及其受体GPR1在高脂饲料喂养小鼠的腹股沟脂肪以及肩胛下脂肪中的表达高于正常饲料组;b.沉默C57BL/6小鼠体内Chemerin或GPR1基因的表达后,肝脏以及腹股沟脂肪组织中脂质的累积受到抑制;c.3T3-L1细胞在体外分化成熟过程中,Chemerin和GPR1也呈高表达的趋势,沉默分化前3T3-L1细胞中Chemerin或GPR1基因的表达后,3T3-L1细胞向脂肪细胞的分化受到影响,降低了脂肪细胞中脂质的累积以及与脂质代谢相关基因的表达,改变了成熟脂肪细胞中新陈代谢功能.这些结果提示,Chemerin及其受体GPR1可能在小鼠脂肪累积中具有调控作用.综上所述,Chemerin/GPR1可能是一种调节脂肪组织中脂质累积的潜在信号通路,为肥胖症等代谢紊乱疾病的治疗提供了可能的作用靶点.  相似文献   
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The RabGAP AS160/TBC1D4 controls exocytosis of the insulin-sensitive glucose transporter Glut4 in adipocytes. Glut4 is internalized and recycled through a highly regulated secretory pathway in these cells. Glut4 also cycles through a slow constitutive endosomal pathway distinct from the fast transferrin (Tf) receptor recycling pathway. This slow constitutive pathway is the only Glut4 cycling pathway in undifferentiated fibroblasts. The α2-macroglobulin receptor LRP1 cycles with Glut4 and the Tf receptor through all three exocytic pathways. To further characterize these pathways, the effects of knockdown of AS160 substrates on the trafficking kinetics of Glut4, LRP1, and the Tf receptor were measured in adipocytes and fibroblasts. Rab10 knockdown decreased cell surface Glut4 in insulin-stimulated adipocytes by 65%, but not in basal adipocytes or in fibroblasts. This decrease was due primarily to a 62% decrease in the rate constant of Glut4 exocytosis (kex), although Rab10 knockdown also caused a 1.4-fold increase in the rate constant of Glut4 endocytosis (ken). Rab10 knockdown in adipocytes also decreased cell surface LRP1 by 30% by decreasing kex 30–40%. There was no effect on LRP1 trafficking in fibroblasts or on Tf receptor trafficking in either cell type. These data confirm that Rab10 is an AS160 substrate that limits exocytosis through the highly insulin-responsive specialized secretory pathway in adipocytes. They further show that the slow constitutive endosomal (fibroblast) recycling pathway is Rab10-independent. Thus, Rab10 is a marker for the specialized pathway in adipocytes. Interestingly, mathematical modeling shows that Glut4 traffics predominantly through the specialized Rab10-dependent pathway both before and after insulin stimulation.  相似文献   
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Vanadate and insulin both function as unique complete mitogens for SV40-transformed 3T3T cells, designated CSV3-1, but not for nontransformed 3T3T cells. The mitogenic effects induced by vanadate and insulin in CSV3-1 cells are mediated by different signaling mechanisms. For example, vanadate does not stimulate the tyrosine phosphorylation of the insulin receptor -subunit nor the 170 kDa insulin receptor substrate-1. Instead, vanadate induces a marked increase in tyrosine phosphorylation of 55 and 64 kDa proteins that is not observed in insulin-stimulated CSV3-1 cells. Perhaps most interestingly, vanadate-induced mitogenesis is associated with the selective induction ofc-jun andjunB expression without significantly inducingc-fos orc-myc. Furthermore, treatment of CSV3-1 cells with genistein abolishes the effects of vanadate on protein tyrosine phosphorylation andc-jun induction. These and related data suggest that modulation of protein tyrosine phosphorylation andc-jun andjunB expression may serve the critical roles in mediating vanadate-induced mitogenesis in SV40-transformed cells.  相似文献   
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Adipocyte growth and development are complex and precisely orchestrated processes. Several microRNAs have been identified as critical regulators of the adipocyte growth and development. Recently, bta-miR-204 was found to be involved in adipogenesis; however, the underlying molecular mechanism involved in bta-miR-204-mediated regulation of proliferation, differentiation, and apoptosis of adipocytes is not fully understood or elucidated. In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Cell Counting Kit-8, EdU, flow cytometer, Oil Red O staining, and the western blot assays were used to assess the role of bta-miR-204 in adipocyte growth and development. Overexpression of bta-miR-204 had no significant effect on 3T3-L1 cell proliferation. The forced expression of bta-miR-204 promoted 3T3-L1 cell differentiation. Meanwhile, overexpression of bta-miR-204 upregulated the expression of Bax and downregulated the expression of Bcl-2 both at messenger RNA and protein levels, which suggested that bta-miR-204 can promote 3T3-L1 cell apoptosis. Using bioinformatic analysis, dual-luciferase reporter system and qRT-PCR, TGFBR2, and ELOVL6 were identified as the direct target genes of bta-miR-204. Therefore, our study provides a novel insight into the role of bta-miR-204 in the regulation of adipocyte growth and development, which may provide a novel therapeutic alternative against obesity.  相似文献   
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It has been demonstrated that the composition of molecular species of adipose tissue triacylglycerols (TGs) from farm animals are not equally synthesized and that some molecular species are preferentially synthesized. The objective of the present study was to determine whether exogenous fatty acids (FAs) would affect the TG composition. To this end, the composition of TG molecular species stored in porcine adipocytes differentiated with several long-chain FAs was analyzed by gas chromatography. The addition of each FA for 6 d increased TG molecular species having two or three added FAs. However, the molecular species compositions at 15 d after the addition of each FA resembled those of cells with no added FAs. Moreover, some common molecular species in all experimental cells increased, as well as cells with no added FAs. It was concluded that the addition of FAs increases the contents of specific molecular species, but does not affect the synthetic processes of individual TG molecular species.  相似文献   
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