Intestinal regulation of fatty acid receptors in lean and overweight humans (#79)
Background: Fatty acid (FA) receptors in the lingual and intestinal mucosa sense dietary fats, and in the intestine, may trigger gut hormone release to control appetite and food intake. Altered expression and/or function of intestinal FA receptors may impair appetite regulation in obesity, however data in humans is limited. Here, we compared duodenal expression of FA receptors in healthy and overweight subjects at baseline and following acute intraduodenal fat infusion.
Methods: Fasted lean (BMI: 21.6 ± 1.4 kg.m2, n = 7) and overweight (BMI: 26.8 ± 1.0, n = 8) healthy volunteers without type 2 diabetes underwent unsedated endoscopy, and 5 mucosal biopsies were collected from the proximal duodenum at baseline, and after a 30 min intraduodenal lipid infusion (10% Intralipid®; 2kcal/min). RNA was extracted from biopsies (commercial kit), and mRNA expression of the FA receptors GPR120, GPR40, GPR119 and the FA transporter CD36 determined using quantitative RT-PCR relative to that of the housekeeper beta-2 microglobulin.
Results: Relative duodenal expression of GPR40 and CD36 was increased, while GPR119 and 120 was decreased in overweight compared to lean subjects, however these changes were not significant; FA receptor expression was unaltered by acute lipid exposure in either group. Changes in expression of GRP40 and GPR119 during lipid infusion, in contrast, were significantly and positively correlated in both lean (r2 = 0.79; P < 0.01) and overweight subjects (r2 = 0.92; P < 0.001).
Conclusion: In humans, overweight is not associated with dysregulated expression of the intestinal FA receptors. Transcriptional control of the short-chain FA receptor, GRP40, and oleoylethanolamide receptor, GRP119, however, is likely to be positively regulated by a common regulatory pathway in the human duodenum during lipid exposure. This active study will yield new information on whether dysregulation of intestinal FA receptors, and/or their signalling, occur in humans with obesity.