Role of GPR81 in lactate-mediated reduction of adipose lipolysis |
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Authors: | Cai Tian-Quan Ren Ning Jin Lan Cheng Kang Kash Shera Chen Ruoping Wright Samuel D Taggart Andrew K P Waters M Gerard |
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Affiliation: | a Department of Cardiovascular Diseases, Merck Research Laboratories, RY80T-A100, 126 East Lincoln Avenue, Rahway, NJ 07065, USA b Arena Pharmaceuticals Inc., San Diego, California 92121, USA c Deltagen, Inc. San Carlos, California 94070, USA |
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Abstract: | Heavy exercise or oxygen deficit often links with higher levels of arterial lactate and lower levels of plasma free fatty acids (FFA). Treatment with lactate reduces circulating levels of FFA in vivo and lipolysis in adipose tissues in vitro. However, the underlying mechanism has remained unclear. Here we employ pharmacological and genetic approaches to show that GPR81, an orphan G-protein-coupled receptor with relatively restricted expression in the adipose tissues, functions as a receptor for lactate and can mediate an anti-lipolytic effect of lactate. GPR81 may thus function as a sensor of lactate that can modulate the FFA pool under exercise or conditions of oxygen deficit. |
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Keywords: | Lactic acid Orphan GPCR Exercise Oxygen deficit Free fatty acids |
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