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

• Main Authors: Jacob Z. Longenecker (Author), Jennifer M. Petrosino (Author), Colton R. Martens (Author), Scott A. Hinger (Author), Charlotte J. Royer (Author), Lisa E. Dorn (Author), Daniel A. Branch (Author), Joan Serrano (Author), Kristin I. Stanford (Author), George A. Kyriazis (Author), Kedryn K. Baskin (Author), Federica Accornero (Author)
• Format: Book
• Published: Elsevier, 2021-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

2212-8778
10.1016/j.molmet.2021.101343