title: Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids.
abstract: G protein-coupled receptor 43 (GPR43) has been identified as a receptor for short-chain fatty acids that include acetate and propionate. A potential involvement of GPR43 in immune and inflammatory response has been previously suggested because its expression is highly enriched in immune cells. GPR43 is also expressed in a number of other tissues including adipocytes; however, the functional consequences of GPR43 activation in these other tissues are not clear. In this report, we focus on the potential functions of GPR43 in adipocytes. We show that adipocytes treated with GPR43 natural ligands, acetate and propionate, exhibit a reduction in lipolytic activity. This inhibition of lipolysis is the result of GPR43 activation, because this effect is abolished in adipocytes isolated from GPR43 knockout animals. In a mouse in vivo model, we show that the activation of GPR43 by acetate results in the reduction in plasma free fatty acid levels without inducing the flushing side effect that has been observed by the activation of nicotinic acid receptor, GPR109A. These results suggest a potential role for GPR43 in regulating plasma lipid profiles and perhaps aspects of metabolic syndrome.
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, USA.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Ge
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Li
authors.forename: Jennifer
authors.initials: J
authors.lastname: Weiszmann
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Helene
authors.initials: H
authors.lastname: Baribault
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D041721:3T3-L1 Cells; D019342:Acetic Acid / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005483:Flushing / Q000139:chemically induced; D008066:Lipolysis / Q000187:drug effects / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009525:Niacin / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D005230:Fatty Acids, Nonesterified; C506481:Ffar2 protein, mouse; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D009525:Niacin; C029658:propionic acid; D019342:Acetic Acid