Hypothalamic neuronal toll-like receptor 2 protects against age-induced obesity

Sci Rep. 2013;3:1254. doi: 10.1038/srep01254. Epub 2013 Feb 13.

Abstract

Toll-like receptors (TLRs) are traditionally associated with immune-mediated host defense. Here, we ascribe a novel extra-immune, hypothalamic-associated function to TLR2, a TLR-family member known to recognize lipid components, in the protection against obesity. We found that TLR2-deficient mice exhibited mature-onset obesity and susceptibility to high-fat diet (HFD)-induced weight gain, via modulation of food intake. Age-related obesity was still evident in chimeric mice, carrying comparable TLR2(+) immune cells, suggesting a non-hematopoietic-related involvement of this receptor. TLR2 was up-regulated with age or HFD in pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, a brain area participating in central-metabolic regulation, possibly modulating the hypothalamic-anorexigenic peptide, α-melanocyte-stimulating hormone (α-MSH). Direct activation of TLR2 in a hypothalamic-neuronal cell-line via its known ligands, further supports its capacity to mediate non-immune related metabolic regulation. Thus, our findings identify TLR2 expressed by hypothalamic neurons as a potential novel regulator of age-related weight gain and energy expenditure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Cell Line
  • Diet, High-Fat
  • Energy Metabolism
  • Hypothalamus / metabolism*
  • Ligands
  • Mice
  • Obesity / etiology
  • Obesity / metabolism
  • Pro-Opiomelanocortin / metabolism
  • Toll-Like Receptor 2 / deficiency
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*
  • alpha-MSH / metabolism

Substances

  • Ligands
  • Toll-Like Receptor 2
  • alpha-MSH
  • Pro-Opiomelanocortin