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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\u2013specific GIPR knockout (GIPRadipo\u2212\/\u2212) mice and investigated the direct actions of GIP in adipose tissue. Under high-fat diet (HFD)-fed conditions, GIPRadipo\u2212\/\u2212 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\u2212\/\u2212 mice. Plasma levels of interleukin-6 (IL-6), a proinflammatory cytokine that induces insulin resistance, were reduced in HFD-fed GIPRadipo\u2212\/\u2212 mice compared with those in HFD-fed GIPRfl\/fl mice. 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\u2212\/\u2212 mice compared with those of HFD-fed GIPRfl\/fl mice. 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.<\/jats:p>","DOI":"10.2337\/db16-0758","type":"journal-article","created":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T21:01:06Z","timestamp":1484686866000},"page":"868-879","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":95,"title":["Inhibition of Gastric Inhibitory Polypeptide Receptor Signaling in Adipose Tissue Reduces Insulin Resistance and Hepatic Steatosis in High-Fat Diet\u2013Fed Mice"],"prefix":"10.2337","volume":"66","author":[{"given":"Erina","family":"Joo","sequence":"first","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Yamane","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Taura","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Sankoda","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimitaka","family":"Shibue","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanari","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Hamasaki","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuya","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2017,1,17]]},"reference":[{"key":"2022031210355153300_B1","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.2337\/diab.37.12.1595","article-title":"Banting lecture 1988. 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