A growing body of evidence suggests that the capacity of the intestine to sense fatty acids is compromised in obesity. In new research, investigators have found that the intestinal expression of genes that encode three free fatty acid sensors, FFAR1, FFAR4 and CD36, are significantly altered in humans with obesity.

The investigators, recruited individuals who were lean, overweight or with obesity and took biopsy samples from the duodenum before and after a 30-minute infusion of lipids.

At baseline, expression of both FFAR1 and FFAR4 was 62% lower in participants with obesity than in lean counterparts. In participants with obesity, expression of CD36 was 242-fold and 202-fold higher than in lean or overweight individuals, respectively. Baseline expression of GPR119, localised to enteroendocrine cells, was the same in all participants. However, after an infusion of a commercially available 10% lipid emulsion directly into the duodenum, expression of FFAR1 and GPR119 was increased, whereas the expression of CD36 and FFAR4 was unchanged.

Moreover, expression of FFAR1 and FFAR4 was negatively associated, and that of CD36 positively associated, with increasing BMI in participants. GPR119 expression was unrelated to BMI. Finally, as food intake is associated with increased secretion of hormones from gastrointestinal cells, the team also looked at secretion of glucose-dependent insulinotropic polypeptide (GIP) in response to lipid intake. Of the four fatty acid sensors, only the lipid-induced increase in FFAR1 expression correlated with plasma levels of GIP.

The findings highlight that elevated BMI alters the expression of genes that are involved in the capacity to sense and absorb dietary lipids, which might, therefore, further promote the development of obesity.