Studies On The Expression Rules And Lipolysis Mechanism Of TGH

The major physiological role for white adipose tissue (WAT) fat stores is to supply lipid energy when it is needed by other tissues. Altered lipolysis could be an element leading to obesity and interindividual variations in WAT lipolysis are of importance for the rate of weight loss. Conversely, excessive lipolytic rates, in conjunction with impairment in fatty acid utilization by muscle and liver, may be a major contributor to the metabolic abnormalities found in subjects with upper body obesity.Hormone sensitive lipase (HSL) is the first intracellular lipase,which was once considered as the only limited enzyme in lipolysis. With more and more studies on HSL-/- mice , remained 40% basal TG lipase activity suggested that another lipase was involved in intracellular lipolysis. Triacylglycerol hadrolase(TGH) and Adipose Triglyceride Lipase(ATGL) were founded in 2004,then to became the focus on lipid metabolism.We studied on expression rules and lipolysis mechanism of TGH on various levels(fat tissue, adipocyte and molecule) in different species(pig, rat and mice). Meanwhile, the role of TGH in basal lipolysis was analyzed though compared with HSL and ATGL. Moreover expression rules of TGH in different types pig, growth stages and accumulated sites were detected. The relationship of TGH expression with differentiation and lipolysis of adipocyte were also investigated.The adipocyte were treated with Insulin and TNF-α,and analyzed the difference in pathways of lipolysis-enhanced and lipolysis-inhibited with HSL and ATGL. Additionally, cooperation with Research Center, Sainte-Justine Hospital Canada , using gene chip , expression change of TGH during fasting and high-fat diet feeding were determined .The results showed ::1.The expression rules of TGH in different types pig, growth stages and accumulated sites are same as HSL, which proved that TGH expression is negative relatedness with degree of individual obese, reduced with growth stages and higher in visceral adipose than other accumulated sites.2.. The expression of TGH in porcine and rat primary aidpoctye in differentiation were compared The highest expression level of TGH was appeared earlier than the highest value of preadipocyte differentiation ,which was not consistent with it in rat primary adipocyte. Meanwhile, the difference in morphology of both adipocyte during differentiation was determined and analyzed from different aspects such as the change of lipolysis, time series of lipases, transcript factors, notate genes expression, which suggested that the difference of differentiation process in both species was in associate with TGH expression and its role in basal lipolysis. This result demonstrated that rodent is limited as a mode of studying lipid metabolism.3 .The porcine primary adipocyte were treated with different concentration of insulin and TNF-α.,The change of TGH expression in lipolysis-enhanced and lipolysis-inhibited pathways was observed in porcine primary adipocyte.The results showed that TGH was changed little during these processes,.We also found that the change of TGH only could be detected for hormone treating a long time, which further proved that TGH might play a role in basal lipolysis.4 .The change of TGH expression and role in lipolysis during fasting were analyzed by gene chip, the result showed that the change of TGH was more significant than HSL and ATGL during this process, beside , enhanced basal lipolysis was observed , which suggested that TGH might afford major role during fasting.We also found that although lipolysis was enhanced after stimulated by CL, its difference was not significant .this proved again that TGH play its role not in hormone-stimulated condition ,but under basal condition.5. Using gene chip ,we analyzed the change of TGH and lipolysis after feeding high fat diet. The results showed that fat diet feeding could course weight gaining, the expression of lipases in adipocyte were decreased , the change of TGH expression is most significantly compared with HSL and ATGL and extremely significant when compared with the group feed with basal diet, providing that decreased metabolism during this process resulted from the decreased TGH expression.6. The expression of TGH is lower in adipocyte of high-weight gainer than low-weight gainer. We found that unlike other lipase, only TGH mRNA expression was changed in both individuals(P<0.001).This result suggested that TGH was the key factor influencing lipid metabolism and obese sensitivity.7. According to the High-fat diet and fasting of gene expression analysis on the microarray dataes, using the multi-database and softwares, we draw the networks of TGH with other genes with molecular regulation mechanism .