Study on the Lipolytic Function of GPR43 and Its Reduced Expression by DHA

Sun, Chao;Hou, Zengmiao;Wang, Li

  • Received : 2008.07.29
  • Accepted : 2008.12.03
  • Published : 2009.04.01


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 $\gamma$ gene ($PPAR_{\gamma}$, 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.


GPR43;Pig;Mouse;Adipose Tissue;Adipocyte, Lipolysis;DHA


  1. Dolinsky, V. W., D. Gilham, G. M. Hatch, L. B. Agellon, R. R. Lehner and D. E. Vance. 2003. Regulation of triacylglycerol hydrolase expression by dietary fatty acids and peroxisomal proliferator-activated receptors. Biochim. Biophys. Acta. 1635:20-28
  2. Gibbons, G. F., K. Islam and R. J. Pease. 2000. Mobilisation of triacylglycerol stores. Biochim. Biophys. Acta. 1483(1):37-57
  3. Grimaldi, P. A. 2001. The roles of PPARs in adipocyte differentiation. Prog Lipid Res. 40:269-281
  4. Liu, B. H., Y. C. Wang, C. F. Kuo, W. M. Cheng, T. F. Shen and S. T. Ding. 2005. The effects of docosahexaenoic acid oil and soybean oil on the expression of lipid metabolism related mRNA in pigs. Asian-Aust. J. Anim. Sci. 18(10):1451-1456
  5. Sawzdargo, M., S. R. George, T. Nguyen, S. Xu, L. F. Kolakowski and B. F. O'Dowd. 1997. A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1. Biochem. Biophys. Res. Commun. 239:543-547
  6. Schoonjans, K., J. PeinadoOnsurbe, A. M. Lefebvre, R. A. Heyman, M. Briggs, S. Deeb, B. Staels and J. Auwerx. 1996. PPAR alpha and PPAR gamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. Embo. J. 15:5336-5348
  7. Howard, A. D., G. McAllister, S. D. Feighner, Q. Liu, R. P. Nargund, L. H. Van der Ploeg and A. A. Patchett. 2001. Orphan G-protein-coupled receptors and natural ligand discovery. Trends Pharmacol. Sci. 22:132-140
  8. Brown, A. J., S. M. Goldsworthy, A. A. Barnes, M. M. Eilert, L. Tcheang, D. Daniels, A. I. Muir, M. J. Wigglesworth, I. Kinghorn, N. J. Fraser, N. B. Pike, J. C. Strum, K. M. Steplewski, P. R. Murdock, J. C. Holder, F. H. Marshall, P. G. Szekeres, D. S. Wilson, M. R. Igna, S. M. Foord, A. Wise and S. J. Dowell. 2003. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278:11312-11319
  9. Kotarsky, K., N. E. Nilsson, E. Flodgren, C. Owman and B. Olde. 2003. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs. Biochem. Biophys. Res. Commun. 301:406-410
  10. Le Poul, E., C. Loison, S. Struyf, J. Y. Springael, V. Lannoy, M. E. Decobecq, S. Brezillon, V. Dupriez, G. Vassart, J. Van Damme, M. Parmentier and X. Detheux. 2003. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278(8):25481-25489
  11. Carmen, G. Y. and S. M. Victor. 2006. Signalling mechanisms regulating lipolysis. Cell Signal. 18:401-408
  12. Rivellese, A. A., R. Giacco, G. Annuzzi, C. De Natale, L. I. Patt, L. Di Marino, V. Minerva, G. Costabile, C. Santangelo, R. Masella and G. Riccardi. 2007. Effects of monounsaturated vs. saturated fat on postprandial lipemia and adipose tissue lipases in type 2 diabetes. Clin. Nutr. 27(1):133-141
  13. Gongshe Yang, Huai Qiu and Xingzhong Lu. 1997. Cytological and morphological studies on adipose development in wwine. Journal of Northwest Sci-Tech University of Agriculture and Forestry 25:8-14
  14. Hongmei, S., Y. Gongshe and S. Chao. 2007. Co-culture of preadipocytes and myogenic satellite cells in porcine. J. Agr Biotech. 15:617-621
  15. Senga, T., S. Iwamoto, T. Yoshida, T. Yokota, K. Adachi, E. Azuma, M. Hamaguchi and T. Iwamoto. 2003. LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3. Blood. 101:1185-1187
  16. Kim, H. K., M. Della-Fera, J. Lin and C. A. Baile. 2006. Docosahexaenoic acid inhibits adipocyte differentiation and induces apoptosis in 3T3-L1 preadipocytes. J. Nutr. 136:2965-2969
  17. Bjorntorp, P. 2000. Metabolic difference between visceral fat and subcutaneous abdominal fat. Diabetes Metab. 26(Suppl. 3):10-12
  18. Hong, Y. H., Y. Nishimura, D. Hishikawa, H. Tsuzuki, H. Miyahara, C. Gotoh, K. C. Choi, D. D. Feng, C. Chen, H. G. Lee, K. Katoh, S. G. Roh and S. Sasaki. 2005. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinol. 146:5092-5099
  19. Andrea, R. N. and E. S. Philipp. 2005. The adipocyte as a drug discovery target. J. Drug Discov. Today. 10:1359-6446
  20. Holm, C., T. G. Kirchgessner, K. L. Svenson, G. Fredrikson, S. Nilsson, C. G. Miller, J. E. Shively, C. Heinzmann, R. S. Sparkes and T. Mohandas. 1988. Hormone-sensitive lipase: equence, expression, and chromosomal localization to 19 cent-q13.3. Sci. 241:1503-1506
  21. Nilsson, N. E., K. Kotarsky, C. Owman and B. Olde. 2003. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem. Biophys. Res. Commun. 303:1047-1052
  22. Wei, E., R. Lehner and D. E. Vance. 2005. C/EBPalpha activates the transcription of triacylglycerol hydrolase in 3T3-L1 adipocytes. Biochem. J. 388:959-966
  23. Guo,W., S. H. Wang, H. J. Cao, K. Xu, J. Zhang, Z. L. Du, W. Lu, J. D. Feng, N. Li, C. H. Wu and L. Zhang. 2008. Gene microarray analysis for porcine adipose tissue: Comparison of gene expression between Chinese Xiang Pig and Large White. Asian-Aust. J. Anim. Sci. 21(1):11-18
  24. Soliman, M., K. Kimura, M. Ahmed, D. Yamaji, Y. Matsushita, Y. Okamatsu-Ogura, K. Makondo and M. Saito. 2007. Inverse regulation of leptin mRNA expression by short- and long-chain fatty acids in cultured bovine adipocytes. Domest. Anim. Endocrinol. 33:400-409
  25. Mersmann, H. J. 1998. Lipoprotein and hormone-sensitive lipases in porcine adipose tissue. J. Anim. Sci. 76:1396-1404
  26. Zou, X. T., Z. R. Xu, J. L. Zhu, X. J. Fang and J. F. Jiang. 2007. Effects of dietary dihydropyridine supplementation on laying performance and fat metabolism of laying hens. Asian-Aust. J. Anim. Sci. 20(10):1606-1611

Cited by

  1. Analysis of sequence variability in the pig CART gene and association of polymorphism with fatness traits in a F2 population vol.41, pp.8, 2014,


Supported by : National Nature Science Foundation of China, Chinese Ministry of Education