Exploring the function and regulatory mechanisms of adiponectin and its receptors in pigs
Date Issued
2009
Date
2009
Author(s)
Liu, Bing-Hsien
Abstract
Adiponectin is an adipocyte-derived hormone that plays important roles in regulating glucose and lipid metabolism. Adiponectin receptor 1 and 2 (AdipoR1 & AdipoR2) are the major physiological receptors to mediate the actions of adiponectin in vivo. We successfully cloned the porcine adiponectin and its receptors. The amino acid sequences predicted for the full-length cDNA of porcine adiponectin, AdipoR1, and AdipoR2 were similar to those of the human and mouse, suggesting similar functions of these genes in pigs. In young growing pigs, adiponectin mRNA was up-regulated by fasting in visceral, but not s.c., adipose tissues, whereas AdipoR1 and AdipoR2 mRNA were increased in s.c., but not visceral, adipose tissues. We also found that insulin inhibited the expression of AdipoR2 through the phosphatidylinositol 3-kinase pathway, but the AdipoR1 was not regulated by insulin. Therefore, we speculate that AdipoR1 mediates the function of adiponectin to maintain energy metabolism and AdipoR2 responses to hormonal and nutritional regulation. However, the physiological differences of these two receptors in diet-induced metabolic syndromes are still unclear. Thus, we generated porcine AdipoR1 and R2 transgenic mice and fed the mice with long-term high fat and high sucrose diet to induce obesity. We found that AdipoR1 prevented mice from diet-induced obesity, fatty liver and insulin resistance whereas AdipoR2 had minor effects. Both AdipoR1 and R2 mice fed with high fat and high sucrose diet showed negative feedback regulation of adiponectin. In addition, we found that the multimeric partner of adiponectin (C1qtnf9) in the adipose tissue was decreased when mice fed with the high fat and high sucrose diet. AdipoR2 but not AdipoR1 mice tended to downregulate the expression of C1qtnf9 in the adipose tissue. In contrast, AdipoR1 but not AdipoR2 transgenic mice have stronger effects on preventing diet-induced insulin resistance. Only AdipoR1 transgene increases the expression of Pck1, a glyceroneogenesis enzyme in the adipose tissue. AdipoR1 transgenic mice may increase Pck1 to promote glyceroneogenesis in the adipose tissue to reduce glucose intolerance. Such effect may activate the flux of glyceride-glycerol function to increase glucose tolerance in the adipose tissue. We clearly defined the function of AdipoR1 on preventing diet-induced metabolic syndromes and such findings could lead to development of new therapeutic strategy for the metabolic syndrome and obesity.
Subjects
pig
adipokine
adiponectin receptor
insulin
obesity
SDGs
Type
thesis
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