Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea.
Bio-Medical Institute of Technology (BMIT), University of Ulsan College of Medicine, Seoul 05505, Korea.
Int J Mol Sci. 2019 Jul 18;20(14):3520. doi: 10.3390/ijms20143520.
The high abundance of mitochondria and the expression of mitochondrial uncoupling protein 1 (UCP1) confer upon brown adipose tissue (BAT) the unique capacity to convert chemical energy into heat at the expense of ATP synthesis. It was long believed that BAT is present only in infants, and so, it was not considered as a potential therapeutic target for metabolic syndrome; however, the discovery of metabolically active BAT in adult humans has re-stimulated interest in the contributions of BAT metabolic regulation and dysfunction to health and disease. Here we demonstrate that brown adipocyte autophagy plays a critical role in the regulation BAT activity and systemic energy metabolism. Mice deficient in brown adipocyte autophagy due to BAT-specific deletion of -a gene essential for autophagosome generation-maintained higher mitochondrial content due to suppression of mitochondrial clearance and exhibited improved insulin sensitivity and energy metabolism. Autophagy was upregulated in BAT of older mice compared to younger mice, suggesting its involvement in the age-dependent decline of BAT activity and metabolic rate. These findings suggest that brown adipocyte autophagy plays a crucial role in metabolism and that targeting this pathway may be a potential therapeutic strategy for metabolic syndrome.
线粒体含量高和线粒体解偶联蛋白 1（UCP1）的表达赋予棕色脂肪组织（BAT）将化学能转化为热量而不依赖于 ATP 合成的独特能力。长期以来，人们一直认为 BAT 仅存在于婴儿中，因此，它不被认为是代谢综合征的潜在治疗靶点；然而，成年人体内代谢活跃的 BAT 的发现重新激发了人们对 BAT 代谢调节和功能障碍对健康和疾病的影响的兴趣。在这里，我们证明棕色脂肪细胞自噬在调节 BAT 活性和全身能量代谢中起着关键作用。由于棕色脂肪细胞特异性缺失生成自噬体所必需的基因，棕色脂肪细胞自噬缺失的小鼠由于抑制了线粒体清除而保持了更高的线粒体含量，并表现出改善的胰岛素敏感性和能量代谢。与年轻小鼠相比，老年小鼠的 BAT 中自噬上调，提示其参与了 BAT 活性和代谢率随年龄增长而下降的过程。这些发现表明，棕色脂肪细胞自噬在代谢中起着至关重要的作用，靶向这条途径可能是治疗代谢综合征的一种潜在策略。
