Expression of the fatty acid receptor GPR120 in the gut of diet-induced-obese rats and its role in GLP-1 secretion.

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

Expression of GPR120 in the intestine of DR and DIO rats aged 6 (a) and 12 (b) months.

<p>An L-cell rich part of the intestine (distal ileum) was used for RNA isolation and subsequent quantification by PCR. Two way ANOVA revealed a main effect of both genotype at 6 and 12 months of age (F = 96.15, P<0.001 and F = 14.42, p = <0.001 respectively). There was a main effect of diet at 6 but not 12 months of age (F = 4.69, p = 0.04 and F = 0.16, p = 0.69 respectively). There was no interaction between genotype and diet at 6 or 12 months. One way ANOVA showed statistical differences between both chow and HE fed DR and DIO rats at 6 months of age (p<0.001), and chow and HE fed DIO rats at 12 months of age (p<0,05). * = p<0.05; *** = <0.001.</p

Plasma levels of insulin (a) and active GLP-1 (b) upon gavage with ALA or OA in Sprague-Dawley rats.

<p>Sprague-Dawley rats were gavaged with vehicle or 28 mg/kg ALA/OA, and the levels of active GLP-1 and insulin were determined. N = 6. Two-way ANOVA with Bonferroni’s multiple comparisons correction (repeated measures) revealed no differences between GLP-1 or insulin plasma levels after administration of ALA when compared both to OA and vehicle treated animals. ALA: acid alpha-linolenic acid; OA: octanoic acid.</p