Florez-Duquet M, Horwitz B A, McDonald R B
Physiology Graduate Group, University of California, Davis 95616, USA.
Am J Physiol. 1998 Jan;274(1):R196-203. doi: 10.1152/ajpregu.1998.274.1.R196.
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 degrees 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 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.
先前的研究表明，与年轻大鼠相比，老年大鼠在暴露于寒冷环境时，棕色脂肪组织（BAT）的冷诱导非寒战产热反应减弱。这种非寒战产热的减少与BAT的质量降低和非寒战产热能力减弱有关。本研究的目的是检验以下假设：26月龄的Fischer 344（F344）雄性大鼠的棕色脂肪对慢性寒冷暴露的营养刺激反应能力受损，表现为细胞数量、质量和解偶联蛋白（UCP）含量增加。为了验证这一假设，我们评估了年轻和老年大鼠BAT对慢性寒冷暴露的反应。我们将6、12和26月龄的F344雄性大鼠暴露于10摄氏度环境中5天，并测量肩胛间BAT（IBAT）的质量、细胞大小和增殖以及线粒体UCP1含量。胰岛素样生长因子I（IGF-I）和去甲肾上腺素的血浆浓度均未因慢性寒冷而影响IBAT质量、细胞增殖或UCP1含量，而6月龄大鼠的IBAT质量在寒冷诱导下增加了近2倍，细胞增殖增加了26倍，UCP1含量增加了4倍。寒冷暴露还分别使6、12和26月龄动物的成熟棕色脂肪细胞大小增加了29%、19%和20%。各年龄段的血浆IGF-I水平均不受寒冷影响，而去甲肾上腺素水平则因寒冷暴露和年龄增长而升高。这些数据支持了以下假设：老年F344大鼠的棕色脂肪对慢性寒冷暴露的营养刺激反应程度不如年轻动物。此外，这些数据表明，本研究中观察到的寒冷或年龄诱导的生长因子水平变化与26月龄大鼠棕色脂肪中缺乏寒冷诱导的前脂肪细胞增殖或UCP1增加无关。
