title: Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion.
abstract: 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.
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors: Kimitaka
authors: K
authors: Shibue
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
authors: Shunsuke
authors: S
authors: Yamane
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
authors: Norio
authors: N
authors: Harada
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
authors: Akihiro
authors: A
authors: Hamasaki
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
authors: Kazuyo
authors: K
authors: Suzuki
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
authors: Erina
authors: E
authors: Joo
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
authors: Kanako
authors: K
authors: Iwasaki
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
authors: Daniela
authors: D
authors: Nasteska
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
authors: Takanari
authors: T
authors: Harada
authors: Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;
authors: Yoshitaka
authors: Y
authors: Hayashi
authors: Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; and.
authors: Yasuhiro
authors: Y
authors: Adachi
authors: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Yuji
authors: Y
authors: Owada
authors: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors: Ryoichi
authors: R
authors: Takayanagi
authors: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan; inagaki@metab.kuhp.kyoto-u.ac.jp.
authors: Nobuya
authors: N
authors: Inagaki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000502:physiology*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000502:physiology*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism
chemical_list: D004041:Dietary Fats; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D005749:Gastric Inhibitory Polypeptide; D005947:Glucose
keywords: fatty acid-binding protein 5; gastric inhibitory polypeptide; incretin; obesity