期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 308, 期 7, 页码 E583-E591出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00543.2014
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Ministry of Health, Labor, and Welfare, Japan
- Integration Research for Agriculture and Interdisciplinary Fields, Japan
- Merck Sharp Dohme (MSD)
- Eli Lilly Japan
- Japan Diabetes Foundation
- Japan Association for Diabetes Education and Care
- Suzuken Memorial Foundation
- Novo Nordisk Pharma
- Shiratori Pharmaceutical
- Roche Diagnostics
- MSD
- Japan Tobacco
- Nippon Boehringer Ingelheim
- Takeda
- Dainippon Sumitomo Pharma
- Astellas Pharma
- Daiichi-Sankyo
- Mitsubishi Tanabe Pharma
- Grants-in-Aid for Scientific Research [25293210, 25461344, 24659451, 24390047, 25461345] Funding Source: KAKEN
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 (GIP(gfp/gfp))-FABP5(+/+) mice and GIP(gfp/gfp)-FABP5(-/-) mice, in which GIP is genetically deleted. These results demonstrate that bile efficiently amplifies fat-induced GIP secretion and that FABP5 contributes to the development of DIO in a GIP-dependent manner.
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