Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion

Kimitaka Shibue, Shunsuke Yamane, Norio Harada, Akihiro Hamasaki, Kazuyo Suzuki, Erina Joo, Kanako Iwasaki, Daniela Nasteska, Takanari Harada, Yoshitaka Hayashi, Yasuhiro Adachi, Yuji Owada, Ryoichi Takayanagi, Nobuya Inagaki

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)E583-E591
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number7
Publication statusPublished - 2015
Externally publishedYes


  • Fatty acid-binding protein 5
  • Gastric inhibitory polypeptide
  • Incretin
  • Obesity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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