SOCS3 Regulate Porcine Preadipocytes Differentiation By Negative Feedback Inhibition Of Leptin Signaling

Adipose tissue has endocrinic function which can secrete many kinds of adipokines. These cytokines affect the metabolism of adipose tissue and the whole body of the organism. Leptin is one of cytokines secreted by adipocytes. Leptin regulate energy homeostasis and body weight by controlling both behavior and metabolic responses in central nervous system. Adipose tissue is not only the source, but also the target point of leptin. Leptin can directly inhibits lipogenesis and stimulates lipolysis and fatty acid oxidation. SOCS3 is a feedback regulation factor of leptin signal. Many phenomenon suggests that SOCS3 plays an important role in the processof leptin regulate differentiation and lipogenesis of adipocyte. But until recently now, the regulation and it mechanism of SOCS3 in leptin signal in adipocytes have not be yet directly and systematicly studied.Therefore, in this study we used the pig as experimental animal,using cellculture, RT-PCR, western blot and RNA interference, and other methods, studied the regulation of SOCS3 in leptin signal transduction and its mechanism of SOCS3 in leptin inhibit adipocyte differentilation. The results achieved were as follows:1 leptin stimulate successfully induce leptin resistence in porcine preadipocytes, and the level of SOCS3 was increased. The result suggested that leptin increase the level of STAT3 phosphorylation in a time-dependent manner on porcine preadipocyte, but after it reach to peak at 16h, it become decrease. These results suggested that chronicity stimulate decrease the sensitivity of LEPRb, and result in leptin resistence. Simultaneously,the expression of SOCS3 was increased. So it suggest that leptin resistence was mainly result from SOCS3.2 successfully constructed the recombinant lentivirus interfering vector target on porcine SOCS3 gene. SOCS3-shRNA3 Stablely inhibit the expression of SOCS3, and the interference efficiency is approximate 70%(p<0.05). The inhibition of leptin on adpocyte differention was increased after decrease the expression of SOCS3 by RNA interference.3 Studied the preliminary mechanism of SOCS3 Gene regulate the differention of porcine adipocyte through leptin signal, the result investigated that SOCS3 attenuation the effect of leptin on the differentiation of porcine preadipocyte by inhibit SHP2/MAPK pathway. Compare with control, the sensitivity that SHP2/MAPK pathway respond to leptin was enhanced. the expression of PPAR-γwas significantly decreased. The result suggested, SOCS3 attenuation the effect of leptin on the differentiation of porcine preadipocyte by inhibit SHP2/MAPK pathway.