{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:21:09Z","timestamp":1784557269053,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:p>\n                    Bone morphogenetic proteins (BMPs) are secreted ligands that belong to the transforming growth factor-\u03b2 (TGF-\u03b2) superfamily. BMP7 has been reported to play a role in reversing obesity and regulating appetite in the hypothalamus. Whether BMP9 plays a central role in regulating glucose metabolism and insulin sensitivity remains unclear. Here, we investigated the impact of central BMP9 signaling and possible route of transmission. We performed intracerebroventricular (ICV) surgery and injected adenovirus expressing BMP9 (Ad-\n                    <jats:italic>BMP9<\/jats:italic>\n                    ) into the cerebral ventricle of mice. Metabolic analysis, hyperinsulinemic-euglycemic clamp test, and analysis of phosphatidylinositol 3,4,5-trisphosphate (PIP3) formation were then performed. Real-time PCR and Western blotting were performed to detect gene expression and potential pathways involved. We found that hypothalamic BMP9 expression was downregulated in obese and insulin-resistant mice. Overexpression of BMP9 in the mediobasal hypothalamus reduced food intake, body weight, and blood glucose level, and elevated the energy expenditure in high-fat diet (HFD)-fed mice. Importantly, central treatment with BMP9 improved hepatic insulin resistance (IR) and inhibited hepatic glucose production in HFD-fed mice. ICV BMP9-induced increase in hepatic insulin sensitivity and related metabolic effects were blocked by ICV injection of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) signaling. In addition, ICV BMP9 promoted the ability of insulin to activate the insulin receptor\/phosphoinositide 3-kinase (PI3K)\/Akt pathway in the hypothalamus. Thus, this study provides insights into the potential mechanism by which central BMP9 ameliorates hepatic glucose metabolism and IR via activating the mTOR\/PI3K\/Akt pathway in the hypothalamus.\n                  <\/jats:p>","DOI":"10.1530\/joe-19-0591","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T10:15:47Z","timestamp":1608286547000},"page":"221-235","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":8,"title":["Hypothalamic BMP9 suppresses glucose production by central PI3K\/Akt\/mTOR pathway"],"prefix":"10.1530","volume":"248","author":[{"given":"Yirui","family":"He","sequence":"first","affiliation":[{"name":"1The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China"},{"name":"2Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"1The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Luo","sequence":"additional","affiliation":[{"name":"1The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Chen","sequence":"additional","affiliation":[{"name":"2Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengliu","family":"Yang","sequence":"additional","affiliation":[{"name":"1The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"3Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvest F","family":"Gu","sequence":"additional","affiliation":[{"name":"4Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Karolinska Institutet, Huddinge, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangyi","family":"Yang","sequence":"additional","affiliation":[{"name":"1The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China"},{"name":"2Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"1The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/248\/2\/JOE-19-0591.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/248\/2\/JOE-19-0591.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:57:05Z","timestamp":1784555825000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/248\/2\/221-235\/5492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/joe-19-0591","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2]]}}}