Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages

Biochem Biophys Res Commun. 2011 Sep 30;413(3):454-9. doi: 10.1016/j.bbrc.2011.08.117. Epub 2011 Aug 30.

Abstract

Chronic low-level inflammation is associated with obesity and a sedentary lifestyle, causing metabolic disturbances such as insulin resistance. Exercise training has been shown to decrease chronic low-level systemic inflammation in high-fat diet (HFD)-induced obesity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Ghrelin is a peptide hormone predominantly produced in the stomach that stimulates appetite and induces growth hormone release. In addition to these well-known functions, recent studies suggest that ghrelin localizes to immune cells and exerts an anti-inflammatory effect. The purpose of the current study was to investigate the role of ghrelin expressed in macrophages in the anti-inflammatory effects of voluntary exercise training. Expression of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein (MCP)-1 and F4/80 was increased in adipose tissue from mice fed a HFD (HFD mice) compared with mice fed a standard diet (SD mice), whereas the expression of these inflammatory cytokines was markedly decreased in mice performing voluntary wheel running during the feeding of a HFD (HFEx mice). The expression of TNF-α was also increased in peritoneal macrophages by a HFD and exercise training inhibited the increase of TNF-α expression. Interestingly, expression of ghrelin in peritoneal macrophages was decreased by a HFD and recovered by exercise training. Suppression of ghrelin expression by siRNA increased TNF-α expression and LPS-stimulated NF-κB activation in RAW264 cells, which is a macrophage cell line. TNF-α expression by stimulation with LPS was significantly suppressed in RAW264 cells cultured in the presence of ghrelin. These results suggest that ghrelin exerts potent anti-inflammatory effects in macrophages and functions as a mediator of the beneficial effects of exercise training.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Cell Line
  • Chemokine CCL2 / metabolism
  • Ghrelin / biosynthesis
  • Ghrelin / physiology*
  • Inflammation / therapy*
  • Macrophages, Peritoneal / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / therapy*
  • Physical Conditioning, Animal*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Ghrelin
  • Tumor Necrosis Factor-alpha