Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Genes Cells. 2010 Feb;15(2):91-100. doi: 10.1111/j.1365-2443.2009.01368.x. Epub 2009 Dec 9.
Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear receptor family, regulating fatty acid degradation in many organs. Two-dimensional SDS-PAGE of brown adipose tissue (BAT) from PPARalpha-null mice produced a higher-density spot. Proteomic analysis indicated that the protein was pyruvate dehydrogenase beta (PDHbeta). To observe PDHbeta regulation in BAT, the organ was stimulated by long-term cold exposure, and the activities of associated enzymes were investigated. Histological and biochemical analyses of BAT showed a significant decrease in the triglyceride content in wild-type mice and some degree of decrease in PPARalpha-null mice on cold exposure. Analyses of molecules related to glucose metabolism showed that the expression of PDHbeta is under PPARalpha-specific regulation, and that glucose degradation ability may decrease on cold exposure. In contrast, analyses of molecules related to fatty acid metabolism showed that numerous PPARalpha/gamma target molecules are induced on cold exposure, and that fatty acid degradation ability in wild-type mice is markedly enhanced and also increases to same degree in PPARalpha-null mice on cold exposure. Thus, this study proposes novel and multiple roles of PPARalpha in BAT.
过氧化物酶体增殖物激活受体α（PPARα）是核受体家族的一员，调节许多器官中的脂肪酸降解。从 PPARα 缺失小鼠的褐色脂肪组织（BAT）中进行二维 SDS-PAGE 产生了一个更高密度的斑点。蛋白质组学分析表明，该蛋白质是丙酮酸脱氢酶β（PDHβ）。为了观察 BAT 中 PDHβ 的调节，通过长期冷暴露刺激该器官，并研究相关酶的活性。BAT 的组织学和生化分析表明，在野生型小鼠中，甘油三酯含量明显下降，在 PPARα 缺失小鼠中也有一定程度的下降。与葡萄糖代谢相关分子的分析表明，PDHβ 的表达受 PPARα 特异性调节，并且在冷暴露时葡萄糖降解能力可能降低。相比之下，与脂肪酸代谢相关的分子的分析表明，大量的 PPARα/γ 靶分子在冷暴露时被诱导，并且野生型小鼠中的脂肪酸降解能力显著增强，在冷暴露时 PPARα 缺失小鼠中也增强到相同程度。因此，本研究提出了 PPARα 在 BAT 中的新的和多种作用。
