Cardiac-derived TGF-β1 confers resistance to diet-induced obesity through the regulation of adipocyte size and function

Autor: Jacob Z. Longenecker, Jennifer M. Petrosino, Colton R. Martens, Scott A. Hinger, Charlotte J. Royer, Lisa E. Dorn, Daniel A. Branch, Joan Serrano, Kristin I. Stanford, George A. Kyriazis, Kedryn K. Baskin, Federica Accornero
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Molecular Metabolism, Vol 54, Iss , Pp 101343- (2021)
Druh dokumentu: article
ISSN: 2212-8778
04303857
DOI: 10.1016/j.molmet.2021.101343
Popis: Regulation of organismal homeostasis in response to nutrient availability is a vital physiological process that involves inter-organ communication. Understanding the mechanisms controlling systemic cross-talk for the maintenance of metabolic health is critical to counteract diet-induced obesity. Here, we show that cardiac-derived transforming growth factor beta 1 (TGF-β1) protects against weight gain and glucose intolerance in mice subjected to high-fat diet. Secretion of TGF-β1 by cardiomyocytes correlates with the bioavailability of this factor in circulation. TGF-β1 prevents adipose tissue inflammation independent of body mass and glucose metabolism phenotypes, indicating protection from adipocyte dysfunction-driven immune cell recruitment. TGF-β1 alters the gene expression programs in white adipocytes, favoring their fatty acid oxidation and consequently increasing their mitochondrial oxygen consumption rates. Ultimately, subcutaneous and visceral white adipose tissue from cadiac-specific TGF-β1 transgenic mice fail to undergo cellular hypertrophy, leading to reduced overall adiposity during high-fat feeding. Thus, TGF-β1 is a critical mediator of heart-fat communication for the regulation of systemic metabolism.
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