title: Hypothalamic neuronal toll-like receptor 2 protects against age-induced obesity.
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.
authors: Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors: Ravid
authors: R
authors: Shechter
authors: Anat
authors: A
authors: London
authors: Yael
authors: Y
authors: Kuperman
authors: Ayal
authors: A
authors: Ronen
authors: Asya
authors: A
authors: Rolls
authors: Alon
authors: A
authors: Chen
authors: Michal
authors: M
authors: Schwartz
mesh_terms: D000375:Aging; D000818:Animals; D002460:Cell Line; D059305:Diet, High-Fat; D004734:Energy Metabolism; D007031:Hypothalamus / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D008024:Ligands; D051195:Toll-Like Receptor 2; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin