Abstract

G protein-coupled receptor 43 (GPR43) is a newly-discovered short-chain free fatty acid receptor and its functions remain to be defined. The objective of this study was to investigate the function of GPR43 on lipolysis. We successfully cloned the GPR43 gene from the pig (EU122439), and measured the level of GPR43 mRNA in different tissues and primary pig adipocytes. The expression level of GPR43 mRNA was higher in adipose tissue and increased gradually with adipocyte differentiation. Then we examined GPR43 mRNA level in different types, growth-stages and various regions of adipose tissue of pigs. The results showed that the expression level of GPR43 mRNA was significantly higher in adipose tissue of obese pigs than in lean pigs, and the expression level also gradually increased as age increased. We further found that the abundance of GPR43 mRNA level increased more in subcutaneous fat than visceral fat. Thereafter, we studied the correlation between GPR43 and lipid metabolism-related genes in adipose tissue and primary pig adipocytes. GPR43 gene had significant negative correlation with hormone-sensitive lipase gene (HSL, r = -0.881, p<0.01) and triacylglycerol hydrolase gene (TGH, r = -0.848, p<0.01) in adipose tissue, and had positive correlation with peroxisome proliferator-activated receptor y gene (PPARy, r = 0.809, p<0.01) and lipoprotein lipase gene (LPL, r = 0.847, p<0.01) in adipocytes. In addition, we fed different concentrations of docosahexaenoic acid (DHA) to mice, and analyzed expression level changes of GPR43, HSL and TGH in adipose. The results showed that DHA down-regulated GPR43 and up-regulated HSL and TGH mRNA levels; GPR43 also had significant negative correlation with HSL (low: r = -0.762, p<0.01; high: r = -0.838, p<0.01) and TGH (low: r = -0.736, p<0.01; high: r = -0.586, p<0.01). Our results suggested that GPR43 is a potential factor which regulates lipolysis in adipose tissue, and DHA as a receptor of GPR43 might promote lipolysis through down-regulating the expression of GPR43 mRNA.

Highlights

  • To support the hypothesis that G protein-coupled receptor 43 (GPR43) is involved in adipocyte differentiation and adipose tissue development, we investigated the relationship between GRP43 expression and the expression levels of other lipolysis genes in adipose tissue (Figure 4) by quantitative PCR

  • GPR43 gene was originally identified in human by VLDL, thereby generating free fatty acids that enter either

  • GPR43 was only expressed in a range of peripheral blood through activation of PPARγ, promoting the hydrolysis of leukocytes, with high levels shown in triglyeride (Schoonjans et al, 1996)

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Summary

Introduction

The pathways that were activated by this receptor include release of intracellular Ca2+ and Adipose tissue plays an important role in regulating ERK1/2 activation and inhibition of cAMP accumulation energy metabolism and functioning as an energy reserve (Le Poul et al, 2003). The key reaction of energy metabolism is adipose acids are most potent agonists for GPR43 Triglycerides (TGs) 2003; Nilsson et al, 2003). GPR43 has been shown were broken down to energy-rich free fatty acids (FFAs) to be present in a variety of tissues, evident in and glycerol (Gibbons et al, 2000). The effective regulation fat stores, inflammatory cells and the gastrointestinal tract

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