Hepatocyte-derived GDF15 suppresses feeding and improves insulin sensitivity in obese mice.

Autor:	Xie B; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Murali A; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Vandevender AM; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Chen J; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Silva AG; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Bello FM; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Chuan B; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Bahudhanapati H; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Sipula I; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Dedousis N; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Shah FA; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., O'Donnell CP; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Alder JK; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Jurczak MJ; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2022 Nov 12; Vol. 25 (12), pp. 105569. Date of Electronic Publication: 2022 Nov 12 (Print Publication: 2022).
DOI:	10.1016/j.isci.2022.105569
Abstrakt:	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 Gdf15 expression is sufficient for changes in circulating levels of GDF15 during obesity and that restoring Gdf15 expression specifically in hepatocytes of Gdf15 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. Competing Interests: The authors declare no competing interests. (© 2022 The Author(s).)
Databáze:	MEDLINE
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