TY - JOUR
T1 - Deorphanization of GPR109B as a receptor for the β-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis
AU - Ahmed, Kashan
AU - Tunaru, Sorin
AU - Langhans, Claus Dieter
AU - Hanson, Julien
AU - Michalski, Christoph W.
AU - Kölker, Stefan
AU - Jones, Patricia M.
AU - Okun, Jürgen G.
AU - Offermanns, Stefan
PY - 2009/8/14
Y1 - 2009/8/14
N2 - The orphan G-protein-coupled receptor GPR109B is the result of a recent gene duplication of the nicotinic acid and ketone body receptor GPR109A being found in humans but not in rodents. Like GPR109A, GPR109B is predominantly expressed in adipocytes and is supposed to mediate antilipolytic effects. Here we show that GPR109B serves as a receptor for the β-oxidation intermediate 3-OH-octanoic acid, which has antilipolytic activity on human but not on murine adipocytes. GPR109B is coupled to Gi-type G-proteins and is activated by 2- and 3-OH-octanoic acid with EC50 values of about 4 and 8 μM, respectively. Interestingly, 3-OH-octanoic acid plasma concentrations reach micromolar concentrations under conditions of increased β-oxidation rates, like in diabetic ketoacidosis or under a ketogenic diet. These data suggest that the ligand receptor pair 3-OH-octanoic acid/GPR109B mediates in humans a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in β-oxidation rates.
AB - The orphan G-protein-coupled receptor GPR109B is the result of a recent gene duplication of the nicotinic acid and ketone body receptor GPR109A being found in humans but not in rodents. Like GPR109A, GPR109B is predominantly expressed in adipocytes and is supposed to mediate antilipolytic effects. Here we show that GPR109B serves as a receptor for the β-oxidation intermediate 3-OH-octanoic acid, which has antilipolytic activity on human but not on murine adipocytes. GPR109B is coupled to Gi-type G-proteins and is activated by 2- and 3-OH-octanoic acid with EC50 values of about 4 and 8 μM, respectively. Interestingly, 3-OH-octanoic acid plasma concentrations reach micromolar concentrations under conditions of increased β-oxidation rates, like in diabetic ketoacidosis or under a ketogenic diet. These data suggest that the ligand receptor pair 3-OH-octanoic acid/GPR109B mediates in humans a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in β-oxidation rates.
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U2 - 10.1074/jbc.M109.019455
DO - 10.1074/jbc.M109.019455
M3 - Article
C2 - 19561068
AN - SCOPUS:69249083201
SN - 0021-9258
VL - 284
SP - 21928
EP - 21933
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 33
ER -