No abstract

GPR120 is a G-protein-coupled receptor whose endogenous ligands have recently been identified as free fatty acids. It has been implicated as playing an important role in the control of lipid and glucose metabolism by regulating the secretion of glucagon-like peptide-1 and cholecystokinin. We have developed an antibody against the extracellular domain of GPR120. The specificity of the antibody was demonstrated by immunoprecipitation, Western blotting, flow cytometry, and immunocytochemistry using GPR120-transfected cells. Immunoreactivity for GPR120 was abundant in the mouse large intestine, lung, and adipose tissue. Furthermore, we found that the expression of GPR120 protein was up-regulated during the adipogenic differentiation of 3T3-L1 cells, which corresponded well with changes in mRNA expression. The anti-GPR120 antibody will be of value for the further study of the function of this nutrient-sensing receptor.

GPR120 and GPR40 are G-protein-coupled receptors whose endogenous ligands are medium- and long-chain free fatty acids, and they are thought to play an important physiological role in insulin release. Despite recent progress in understanding their roles, much still remains unclear about their pharmacology, and few specific ligands for GPR120 and GPR40 besides medium- to long-chain fatty acids have been reported so far. To identify new selective ligands for these receptors, more than 80 natural compounds were screened, together with a reference compound MEDICA16, which is known to activate GPR40, by monitoring the extracellular regulated kinase (ERK) and [Ca(2+)](i) responses in inducible and stable expression cell lines for GPR40 and GPR120, respectively. MEDICA16 selectively activated [Ca(2+)](i) response in GPR40-expressing cells but not in GPR120-expressing cells. Among the natural compounds tested, grifolin derivatives, grifolic acid and grifolic acid methyl ether, promoted ERK and [Ca(2+)](i) responses in GPR120-expressing cells, but not in GPR40-expressing cells, and inhibited the alpha-linolenic acid (LA)-induced ERK and [Ca(2+)](i) responses in GPR120-expressing cells. Interestingly, in accordance with the pharmacological profiles of these compounds, similar profiles of glucagon-like peptide-1 secretion were seen for mouse enteroendocrine cell line, STC-1 cells, which express GPR120 endogenously. Taken together, these studies identified a selective GPR40 agonist and several GPR120 partial agonists. These compounds would be useful probes to further investigate the physiological and pharmacological functions of GPR40 and GPR120.