Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K cells in response to nutrient intake, especially fat. GIP is one of the contributing factors inducing fat accumulation that results in obesity. A recent study shows that fatty acid-binding protein 5 (FABP5) is expressed in murine K cells and is involved in fat-induced GIP secretion. We investigated the mechanism of fat-induced GIP secretion and the impact of FABP5-related GIP response on diet-induced obesity (DIO). Single oral administration of glucose and fat resulted in a 40% reduction of GIP response to fat but not to glucose in whole body FABP5-knockout (FABP5-/-) mice, with no change in K cell count or GIP content in K cells. In an ex vivo experiment using isolated upper small intestine, oleic acid induced only a slight increase in GIP release, which was markedly enhanced by coadministration of bile and oleic acid together with attenuated GIP response in the FABP5-/-sample. FABP5-/-mice exhibited a 24% reduction in body weight gain and body fat mass under a high-fat diet compared with wild-type (FABP5+/+) mice; the difference was not observed between GIP-GFP homozygous knock-in (GIPgfp/gfp)-FABP5+/+mice and GIPgfp/gfp-FABP5-/-mice, in which GIP is genetically deleted. These results demonstrate that bile efficiently amplifies fatinduced GIP secretion and that FABP5 contributes to the development of DIO in a GIP-dependent manner.
|Journal||American Journal of Physiology - Endocrinology and Metabolism|
|Publication status||Published - 2015|
- Fatty acid-binding protein 5
- Gastric inhibitory polypeptide
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology (medical)