title: Inhibition of Gastric Inhibitory Polypeptide Receptor Signaling in Adipose Tissue Reduces Insulin Resistance and Hepatic Steatosis in High-Fat Diet-Fed Mice.
abstract: Gastric inhibitory polypeptide receptor (GIPR) directly induces energy accumulation in adipose tissue in vitro. However, the importance of the direct effect of GIPR signaling on adipose tissue in vivo remains unclear. In the current study, we generated adipose tissue-specific GIPR knockout (GIPRadipo-/-) mice and investigated the direct actions of GIP in adipose tissue. Under high-fat diet (HFD)-fed conditions, GIPRadipo-/-mice had significantly lower body weight and lean body mass compared with those in floxed GIPR (GIPRfl/fl) mice, although the fat volume was not significantly different between the two groups. Interestingly, insulin resistance, liver weight, and hepatic steatosis were reduced in HFD-fed GIPRadipo-/-mice. Plasma levels of interleukin-6 (IL-6), a proinflammatory cytokine that induces insulin resistance, were reduced in HFD-fed GIPRadipo-/-mice compared with those in HFD-fed GIPRfl/flmice. Suppressor of cytokine signaling 3 (SOCS3) signaling is located downstream of the IL-6 receptor and is associated with insulin resistance and hepatic steatosis. Expression levels of SOCS3 mRNA were significantly lower in adipose and liver tissues of HFD-fed GIPRadipo-/-mice compared with those of HFD-fed GIPRfl/flmice. Thus, GIPR signaling in adipose tissue plays a critical role in HFD-induced insulin resistance and hepatic steatosis in vivo, which may involve IL-6 signaling.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Joo
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Harada
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamane
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Taura
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sankoda
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Shibue
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hamasaki
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan inagaki@kuhp.kyoto-u.ac.jp.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000235:genetics; D059305:Diet, High-Fat; D004734:Energy Metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics*; D015850:Interleukin-6 / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008124:Locomotion; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D011964:Receptors, Gastrointestinal Hormone; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; C577686:interleukin-6, mouse; C041086:gastric inhibitory polypeptide receptor