title: Inhibition of gastric inhibitory polypeptide signaling prevents obesity.
abstract: Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance. In contrast, mice lacking the GIP receptor (Gipr(-/-)) fed a high-fat diet were clearly protected from both the obesity and the insulin resistance. Moreover, double-homozygous mice (Gipr(-/-), Lep(ob)/Lep(ob)) generated by crossbreeding Gipr(-/-) and obese ob/ob (Lep(ob)/Lep(ob)) mice gained less weight and had lower adiposity than Lep(ob)/Lep(ob) mice. The Gipr(-/-) mice had a lower respiratory quotient and used fat as the preferred energy substrate, and were thus resistant to obesity. Therefore, GIP directly links overnutrition to obesity and it is a potential target for anti-obesity drugs.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Miyawaki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ban
authors.forename: Yu
authors.initials: Y
authors.lastname: Ihara
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tsukiyama
authors.forename: Heying
authors.initials: H
authors.lastname: Zhou
authors.forename: Shimpei
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Oku
authors.forename: Kinsuke
authors.initials: K
authors.lastname: Tsuda
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiai
authors.forename: Wataru
authors.initials: W
authors.lastname: Mizunoya
authors.forename: Tohru
authors.initials: T
authors.lastname: Fushiki
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Makino
authors.forename: Akira
authors.initials: A
authors.lastname: Tashita
authors.forename: Yukari
authors.initials: Y
authors.lastname: Kobara
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tsubamoto
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Jinnouchi
authors.forename: Takahito
authors.initials: T
authors.lastname: Jomori
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D003433:Crosses, Genetic; D004041:Dietary Fats; D005749:Gastric Inhibitory Polypeptide / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000517:prevention & control*; D011964:Receptors, Gastrointestinal Hormone / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor