Cellular proliferation and UCP content in brown adipose tissue of cold-exposed aging Fischer 344 rats

Abstract

Previous investigations have demonstrated that older vs. younger rats respond to cold exposure with blunted cold-induced nonshivering thermogenesis of brown adipose tissue (BAT). This reduction in nonshivering thermogenesis is associated with reduced mass and blunted nonshivering thermogenic capacity of BAT. The purpose of this study was to test the hypothesis that brown fat in 26-mo-old Fischer 344 (F344) male rats has an impaired capacity to respond to the trophic stimulus of chronic cold exposure with increases in cell number, mass, and uncoupling protein (UCP) content. To test this hypothesis, the response of BAT to chronic cold exposure was evaluated in young and old rats. We exposed 6-, 12-, and 26-mo-old F344 male rats to 10°C for 5 days and measured interscapular BAT (IBAT) mass, cell size and proliferation, and mitochondrial UCP1 content. Plasma concentrations of insulin-like growth factor I (IGF-I) and norepinephrine (NE) were also determined. The 26-mo-old rats did not increase IBAT mass, cell proliferation, or UCP1 content in response to chronic cold, whereas the 6-mo-old rats had a nearly 2-fold cold-induced increase in IBAT mass, a 26-fold increase in cell proliferation, and a 4-fold increase in UCP1 content. Cold exposure also produced an increase of 29, 19, and 20% in mature brown adipocyte cell size of the 6-, 12-, and 26-mo-old animals, respectively. Plasma levels of IGF-I were unaffected by cold at all ages, whereas NE levels were increased by the cold exposure and by increasing age. These data support the hypothesis that brown fat in old F344 rats does not respond to the trophic stimulus of chronic cold exposure to the same degree as younger animals. Moreover, these data indicate that the observed cold- or age-induced changes in levels of growth factors evaluated in this study were not associated with the lack of cold-induced preadipocyte proliferation or increased UCP1 in brown fat of the 26-mo-old rats.