{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:53:27Z","timestamp":1779191607618,"version":"3.51.4"},"reference-count":32,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In both mice and patients with Albright hereditary osteodystrophy, heterozygous inactivating mutations of Gs\u03b1, a ubiquitously expressed G protein that mediates receptor-stimulated intracellular cAMP production, lead to obesity and insulin resistance but only when the mutation is present on the maternal allele. This parent-of-origin effect in mice was shown to be due to Gs\u03b1 imprinting in one or more brain regions. The ventromedial hypothalamus (VMH) is involved in the regulation of energy and glucose homeostasis, but the role of Gs\u03b1 in VMH on metabolic regulation is unknown. To examine this, we created VMH-specific Gs\u03b1-deficient mice by mating Gs\u03b1-floxed mice with SF1-cre mice. Heterozygotes with Gs\u03b1 mutation on either the maternal or paternal allele had a normal metabolic phenotype, and there was no molecular evidence of Gs\u03b1 imprinting, indicating that the parent-of-origin metabolic effects associated with Gs\u03b1 mutations is not due to Gs\u03b1 deficiency in VMH SF1 neurons. Homozygous VMH Gs\u03b1 knockout mice (VMHGsKO) showed no changes in body weight on either a regular or high-fat diet. However, glucose metabolism (fasting glucose, glucose tolerance, insulin sensitivity) was significantly improved in male VMHGsKO mice, with the difference more dramatic on the high-fat diet. In addition, male VMHGsKO mice on the high-fat diet showed a greater anorexigenic effect and increased VMH signal transducer and activator of transcription-3 phosphorylation in response to leptin. These results indicate that VMH Gs\u03b1\/cyclic AMP signaling regulates glucose homeostasis and alters leptin sensitivity in mice, particularly in the setting of excess caloric intake.<\/jats:p>","DOI":"10.1210\/en.2015-1700","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T19:34:24Z","timestamp":1450208064000},"page":"600-610","source":"Crossref","is-referenced-by-count":13,"title":["Gs\u03b1 Deficiency in the Ventromedial Hypothalamus Enhances Leptin Sensitivity and Improves Glucose Homeostasis in Mice on a High-Fat Diet"],"prefix":"10.1210","volume":"157","author":[{"given":"Alta","family":"Berger","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Kablan","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Yao","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thuy","family":"Ho","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Podyma","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee S.","family":"Weinstein","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Chen","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2015,12,15]]},"reference":[{"key":"2020071611592376800_B1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ejphar.2010.10.105","article-title":"Effects of deficiency of the G protein Gs\u03b1 on energy and glucose homeostasis","volume":"660","author":"Chen","year":"2011","journal-title":"Eur J 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