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This version published online on August 25, 2005
Endocrinology, doi:10.1210/en.2005-0545
A more recent version of this article appeared on December 1, 2005
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Submitted on May 5, 2005
Accepted on August 12, 2005

Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43

Yeon-Hee Hong, Yukihiko Nishimura, Daisuke Hishikawa, Hiroaki Tsuzuki, Hisae Miyahara, Chizu Gotoh, Ki-Choon Choi, Dan Dan Fung, Chen Chen, Hong-Gu Lee, Kazuo Katoh, Sang-Gun Roh*, and Shinichi Sasaki

Dept of Food Production Science (Y.-H.H., Y.N., D.H., H.T., H.M., C.G., S.-G.R., S.S.), Shinshu University, Nagano-ken 399-4598, Japan; United Graduate School of Agricultural Science (Y.-H.H.), Gifu University, Japan; Division of Endocrinology and Metabolism (K.-C.C.), Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea; Endocrine Cell Biology (D. F., C.C.), Prince Henry's Institute of Medical Research, PO Box 5152, Clayton 3168, Australia; School of Agricultural Biotechnology, College of Agriculture and Life Science (H.-G.L.), Seoul National University, 56-1 Sillim 9-Dong, Seoul 151-742, Korea and Dept of Animal Physiology, Graduate School of Agricultural Science (K.K.), Tohoku University, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan

* To whom correspondence should be addressed. E-mail: sangroh{at}gipmc.shinshu-u.ac.jp.

It has recently been discovered that G protein-coupled receptors (GPCR) 41 and 43 are characterized by having the short chain fatty acids acetate and propionate as their ligands. The objective of this study was to investigate the involvement of GPCR41, GPCR43 and their ligands in the process of adipogenesis. We measured the levels of GPCR41 and GPCR43 mRNA in both adipose and other tissues of the mouse. GRP43 mRNA expression was higher in four types of adipose tissue than in other tissues, while GPCR41 mRNA was not detected in any adipose tissues. A high level of GPCR43 expression was found in isolated adipocytes but expression level was very low in stromal-vascular cells. Expression of GPCR43 was up-regulated in adipose tissues of mice fed a high-fat diet compared with those fed a normal-fat diet. GPCR43 mRNA could not be detected in confluent and undifferentiated 3T3-L1 adipocytes; however, the levels rose with time after the initiation of differentiation. GPCR41 expression was not detected in confluent and differentiated adipocytes. Acetate and propionate treatments increased lipids present as multiple droplets in 3T3-L1 adipocytes. Propionate significantly elevated the level of GPCR43 expression during adipose differentiation, with up-regulation of PPAR-{gamma}2. Small interfering RNA (siRNA) mediated a reduction of GPCR43 mRNA in 3T3-L1 cells and blocked the process of adipocyte differentiation. In addition, both acetate and propionate inhibited isoproterenol-induced lipolysis in a dose-dependent manner. We conclude that acetate and propionate short chain fatty acids may have important physiological roles in adipogenesis through GPCR43, but not through GPCR41.
Key words: adipogenesis • GPCR43 • GPCR41 • short chain fatty acid




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