Priority Research Paper Volume 12, Issue 10 pp 8766—8789
Muscle-dependent regulation of adipose tissue function in long-lived growth hormone-mutant mice
- 1 Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
- 2 College of Literature, Sciences, and The Arts, University of Michigan, Ann Arbor, Michigan 48109, USA
- 3 University of Michigan Geriatrics Center, Ann Arbor, Michigan 48109, USA
Received: February 1, 2020 Accepted: May 14, 2020 Published: May 28, 2020
https://doi.org/10.18632/aging.103380How to Cite
Copyright © 2020 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Altered adipose tissue may contribute to the longevity of Snell dwarf and growth hormone receptor (GHR) knock-out mice. We report here that white (WAT) and brown (BAT) fat have elevated UCP1 in both kinds of mice, and that adipocytes in WAT depots turn beige/brown. These imply increased thermogenesis and are expected to lead to improved glucose control. Both kinds of long-lived mice show lower levels of inflammatory M1 macrophages and higher levels of anti-inflammatory M2 macrophages in BAT and WAT, with correspondingly lower levels of TNFα, IL-6, and MCP1. Experiments with mice with tissue-specific disruption of GHR showed that these adipocyte and macrophage changes were not due to hepatic IGF1 production nor to direct GH effects on adipocytes, but instead reflect GH effects on muscle. Muscles deprived of GH signals, either globally (GKO) or in muscle only (MKO), produce higher levels of circulating irisin and its precursor FNDC5. The data thus suggest that the changes in adipose tissue differentiation and inflammatory status seen in long-lived mutant mice reflect interruption of GH-dependent irisin inhibition, with consequential effects on metabolism and thermogenesis.