Inhibition of gastric inhibitory polypeptide signaling prevents obesity - PubMed (original) (raw)
doi: 10.1038/nm727. Epub 2002 Jun 17.
Yuichiro Yamada, Nobuhiro Ban, Yu Ihara, Katsushi Tsukiyama, Heying Zhou, Shimpei Fujimoto, Akira Oku, Kinsuke Tsuda, Shinya Toyokuni, Hiroshi Hiai, Wataru Mizunoya, Tohru Fushiki, Jens Juul Holst, Mitsuhiro Makino, Akira Tashita, Yukari Kobara, Yoshiharu Tsubamoto, Takayoshi Jinnouchi, Takahito Jomori, Yutaka Seino
Affiliations
- PMID: 12068290
- DOI: 10.1038/nm727
Inhibition of gastric inhibitory polypeptide signaling prevents obesity
Kazumasa Miyawaki et al. Nat Med. 2002 Jul.
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.
Similar articles
- Attenuated secretion of glucose-dependent insulinotropic polypeptide (GIP) does not alleviate hyperphagic obesity and insulin resistance in ob/ob mice.
Shimazu-Kuwahara S, Harada N, Yamane S, Joo E, Sankoda A, Kieffer TJ, Inagaki N. Shimazu-Kuwahara S, et al. Mol Metab. 2017 Jan 19;6(3):288-294. doi: 10.1016/j.molmet.2017.01.006. eCollection 2017 Mar. Mol Metab. 2017. PMID: 28271035 Free PMC article. - Diet-Induced Obese Mice and Leptin-Deficient Lepob/ob Mice Exhibit Increased Circulating GIP Levels Produced by Different Mechanisms.
Lee E, Miedzybrodzka EL, Zhang X, Hatano R, Miyamoto J, Kimura I, Fujimoto K, Uematsu S, Rodriguez-Cuenca S, Vidal-Puig A, Gribble FM, Reimann F, Miki T. Lee E, et al. Int J Mol Sci. 2019 Sep 10;20(18):4448. doi: 10.3390/ijms20184448. Int J Mol Sci. 2019. PMID: 31509948 Free PMC article. - Inhibition of Gastric Inhibitory Polypeptide Receptor Signaling in Adipose Tissue Reduces Insulin Resistance and Hepatic Steatosis in High-Fat Diet-Fed Mice.
Joo E, Harada N, Yamane S, Fukushima T, Taura D, Iwasaki K, Sankoda A, Shibue K, Harada T, Suzuki K, Hamasaki A, Inagaki N. Joo E, et al. Diabetes. 2017 Apr;66(4):868-879. doi: 10.2337/db16-0758. Epub 2017 Jan 17. Diabetes. 2017. PMID: 28096257 - Physiology of GIP--a lesson from GIP receptor knockout mice.
Yamada Y, Seino Y. Yamada Y, et al. Horm Metab Res. 2004 Nov-Dec;36(11-12):771-4. doi: 10.1055/s-2004-826162. Horm Metab Res. 2004. PMID: 15655707 Review. - Blockade of gastric inhibitory polypeptide (GIP) action as a novel means of countering insulin resistance in the treatment of obesity-diabetes.
Irwin N, Gault VA, O'Harte FPM, Flatt PR. Irwin N, et al. Peptides. 2020 Mar;125:170203. doi: 10.1016/j.peptides.2019.170203. Epub 2019 Nov 13. Peptides. 2020. PMID: 31733230 Review.
Cited by
- The Impact of Gastrointestinal Hormones on Human Adipose Tissue Function.
Radziszewska M, Ostrowska L, Smarkusz-Zarzecka J. Radziszewska M, et al. Nutrients. 2024 Sep 25;16(19):3245. doi: 10.3390/nu16193245. Nutrients. 2024. PMID: 39408213 Free PMC article. Review. - Ciliary localization of GPR75 promotes fat accumulation in mice.
Chávez M, Asthana A, Jackson PK. Chávez M, et al. J Clin Invest. 2024 Oct 1;134(19):e185059. doi: 10.1172/JCI185059. J Clin Invest. 2024. PMID: 39352389 Free PMC article. - Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance.
De Fano M, Malara M, Vermigli C, Murdolo G. De Fano M, et al. Int J Mol Sci. 2024 Aug 8;25(16):8650. doi: 10.3390/ijms25168650. Int J Mol Sci. 2024. PMID: 39201336 Free PMC article. Review. - GLP-1 physiology in obesity and development of incretin-based drugs for chronic weight management.
Holst JJ. Holst JJ. Nat Metab. 2024 Oct;6(10):1866-1885. doi: 10.1038/s42255-024-01113-9. Epub 2024 Aug 19. Nat Metab. 2024. PMID: 39160334 Review. - Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists.
Liu QK. Liu QK. Front Endocrinol (Lausanne). 2024 Jul 24;15:1431292. doi: 10.3389/fendo.2024.1431292. eCollection 2024. Front Endocrinol (Lausanne). 2024. PMID: 39114288 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous