TGF-β1 downregulation in the hypothalamus of obese mice through acute exercise

J Cell Biochem. 2019 Oct;120(10):18186-18192. doi: 10.1002/jcb.29124. Epub 2019 May 29.

Abstract

Obesity and aging lead to abnormal transforming growth factor-β1 (TGF-β1) signaling in the hypothalamus, triggering the imbalance on glucose metabolism and energy homeostasis. Here, we determine the effect of acute exercise on TGF-β1 expression in the hypothalamus of two models of obesity in mice. The bioinformatics analysis was performed to evaluate the correlation between hypothalamic Tgf-β1 messenger RNA (mRNA) and genes related to thermogenesis in the brown adipose tissue (BAT) by using a large panel of isogenic BXD mice. Thereafter, leptin-deficient (ob/ob) mice and obese C57BL/6 mice fed on a high-fat diet (HFD) were submitted to the acute exercise protocol. Transcriptomic analysis by using BXD mouse reference population database revealed that hypothalamic Tgf-β1 mRNA is negatively correlated with genes related to thermogenesis in brown adipose tissue of BXD mice, such as peroxisome proliferator-activated receptor gamma coactivator and is positively correlated with respiratory exchange ratio. In agreement with these results, leptin-deficient (ob/ob) and HFD-fed mice displayed high levels of Tgf-β1 mRNA in the hypothalamus and reduction of Pgc1α mRNA in BAT. Interestingly, an acute exercise session reduced TGF-β1 expression in the hypothalamus, increased Pgc1α mRNA in the BAT and reduced food consumption in obese mice. Our results demonstrated that acute physical exercise suppressed hypothalamic TGF-β1 expression, increasing Pgc1α mRNA in BAT in obese mice.

Keywords: PGC1α; brown adipose tissue; exercise; hypothalamus; obesity; transforming growth factor-β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Animals
  • Diet, High-Fat / adverse effects
  • Down-Regulation*
  • Energy Metabolism / genetics
  • Gene Expression Profiling / methods
  • Hypothalamus / metabolism*
  • Leptin / deficiency
  • Leptin / genetics
  • Male
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / etiology
  • Obesity / genetics*
  • Obesity / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Physical Conditioning, Animal / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thermogenesis / genetics
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Leptin
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA, Messenger
  • Transforming Growth Factor beta1