Abstract
Stimulation of the G protein coupled receptor GPR120 has been shown to have anti-inflammatory and insulin-sensitizing effects, to promote glucagon like peptide-1 (GLP-1) secretion, and to play a key role in sensing dietary fat and control energy balance. In a search for differentially expressed genes potentially involved in food intake and body-weight regulation we identified GPR120 to be differentially regulated in the intestine of selectively bred diet induced obese (DIO) and diet resistant (DR) rats. Subsequently we investigated the effect of GPR120 receptor stimulation with the long chain fatty acid alpha linolenic acid (ALA) on GLP-1 secretion in rats. Independent of diet (high or low fat), GPR120 expression showed a two-fold increase in the intestine of DIO compared to DR rats. In situ hybridization revealed a broad expression of GPR120 in the gut mucosa in both intestinal epithelial and endocrine cells. Using double in situ hybridization GPR120 mRNA did not appear to be enriched in preproglucagon expressing L-cells. In line with the anatomical data, ALA administration did not increase circulating GLP-1 levels. Our data shows a widespread expression of GPR120 in the gut epithelium and can not confirm a major role for GPR120 in the regulation of GLP-1 secretion. The broad expression of GPR120 in the gut epithelium supports reports indicating a putative role of GPR120 as a sensor of dietary fat.
Highlights
GPR120 belongs to a class of five G-protein coupled receptors (GPR40, GPR41, GPR43, GPR84 and GPR120) that are activated by free fatty acids (FFAs)
Two-way ANOVA revealed a main effect of genotype at both time-points (6 months F = 96.15, P, 0.001; 12 months F = 14.42, p =,0.001), with diet induced obese (DIO) rats consistently showing the highest level of GPR120 expression
We found that GPR120 is upregulated in obesity susceptible DIO rats when compared to diet resistant DR rats, and that the expression is not affected by diet
Summary
GPR120 belongs to a class of five G-protein coupled receptors (GPR40, GPR41, GPR43, GPR84 and GPR120) that are activated by free fatty acids (FFAs). Oh et al [5] demonstrated that GPR120 serves as a sensor for v-3-FA In mice they found GPR120 highly expressed in adipose tissue and CD11c+ pro-inflammatory macrophages, and cellular assays showed that activation of the receptor was antiinflammatory (inhibited pro-inflammatory pathways activated by for example TNF-alfa [5]). They showed that the anti-inflammatory signalling properties of GPR120 were involved in the insulin sensitizing and anti-diabetic effects of v-3-FA [5]. Compared to wild type mice, GPR120 KO mice were shown to be more obesity prone on a high-fat diet, to show decreased adipocyte differentiation, fatty liver, glucose intolerance and insulin resistance – all together indicating that GPR120 is an important lipid sensor involved in fat cell differentiation and body-weight regulation [6]
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