title: Orexin restores aging-related brown adipose tissue dysfunction in male mice.
abstract: The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with interscapular BAT morphologic abnormalities and thermogenic dysfunction. In vitro experiments revealed that brown adipocyte differentiation is defective in aged mice. Interscapular brown tissue in aged mice is progressively populated by adipocytes bearing white morphologic characteristics. Aged mice fail to mobilize intracellular fuel reserves from brown adipocytes and exhibit deficiency in homeothermy. Our results suggest a role for orexin (OX) signaling in the regulation of thermogenesis during aging. Brown fat dysfunction and age-related assimilation of fat mass were accelerated in mice in which OX-producing neurons were ablated. Conversely, OX injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.
authors.affiliation: Metabolic Signaling and Disease Program, Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, Florida 32827.
authors.forename: Dyan
authors.initials: D
authors.lastname: Sellayah
authors.forename: Devanjan
authors.initials: D
authors.lastname: Sikder
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D022722:Thermogenesis / Q000187:drug effects* / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins