{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xie B"],"funding":["NHLBI","NIDDK NIH HHS","University of Pittsburgh","NHLBI NIH HHS","National Institutes of Health","NIDDK Division of Diabetes Endocrinology and Metabolic Diseases","Pittsburgh Foundation"],"pagination":["105569"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9708916"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(12)"],"pubmed_abstract":["Growth differentiation factor 15 (GDF15) is a stress-induced secreted protein whose circulating levels are increased in the context of obesity. Recombinant GDF15 reduces body weight and improves glycemia in obese models, which is largely attributed to the central action of GDF15 to suppress feeding and reduce body weight. Despite these advances in knowledge, the tissue-specific sites of GDF15 production during obesity are unknown, and the effects of modulating circulating GDF15 levels on insulin sensitivity have not been evaluated directly. Here, we demonstrate that hepatocyte <i>Gdf15</i> expression is sufficient for changes in circulating levels of GDF15 during obesity and that restoring <i>Gdf15</i> expression specifically in hepatocytes of <i>Gdf15</i> knockout mice results in marked improvements in hyperinsulinemia, hepatic insulin sensitivity, and to a lesser extent peripheral insulin sensitivity. These data support that liver hepatocytes are the primary source of circulating GDF15 in obesity."],"journal":["iScience"],"pubmed_title":["Hepatocyte-derived GDF15 suppresses feeding and improves insulin sensitivity in obese mice."],"pmcid":["PMC9708916"],"funding_grant_id":["R01 DK114012","R01 HL135062","R01HL135062","MR2020 109502","R01DK114012"],"pubmed_authors":["Silva AG","Chen J","Bello FM","Chuan B","Sipula I","O'Donnell CP","Alder JK","Murali A","Jurczak MJ","Vandevender AM","Dedousis N","Bahudhanapati H","Shah FA","Xie B"],"additional_accession":[]},"is_claimable":false,"name":"Hepatocyte-derived GDF15 suppresses feeding and improves insulin sensitivity in obese mice.","description":"Growth differentiation factor 15 (GDF15) is a stress-induced secreted protein whose circulating levels are increased in the context of obesity. Recombinant GDF15 reduces body weight and improves glycemia in obese models, which is largely attributed to the central action of GDF15 to suppress feeding and reduce body weight. Despite these advances in knowledge, the tissue-specific sites of GDF15 production during obesity are unknown, and the effects of modulating circulating GDF15 levels on insulin sensitivity have not been evaluated directly. Here, we demonstrate that hepatocyte <i>Gdf15</i> expression is sufficient for changes in circulating levels of GDF15 during obesity and that restoring <i>Gdf15</i> expression specifically in hepatocytes of <i>Gdf15</i> knockout mice results in marked improvements in hyperinsulinemia, hepatic insulin sensitivity, and to a lesser extent peripheral insulin sensitivity. These data support that liver hepatocytes are the primary source of circulating GDF15 in obesity.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-05-27T18:50:18.062Z","creation":"2025-04-06T14:08:02.805Z"},"accession":"S-EPMC9708916","cross_references":{"pubmed":["36465107"],"doi":["10.1016/j.isci.2022.105569"]}}