Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
University of the Chinese Academy of Sciences, Beijing, China.
Am J Physiol Endocrinol Metab. 2022 Jul 1;323(1):E69-E79. doi: 10.1152/ajpendo.00293.2021. Epub 2022 May 16.
Brown adipose tissue (BAT) is the primary site of adaptive thermogenesis, which is involved in energy expenditure and has received much attention in the field of obesity treatment. By screening a small-molecule compound library of drugs approved by the Food and Drug Administration, pantothenic acid was identified as being able to significantly upregulate the expression of uncoupling protein 1 (UCP1), a key thermogenic protein found in BAT. Pantothenate (PA) treatment decreased adiposity, reversed hepatic steatosis, and improved glucose homeostasis by increasing energy expenditure in C57BL/6J mice fed a high-fat diet. PA also significantly increased BAT activity and induced beige adipocytes formation. Mechanistically, the beneficial effects were mediated by UCP1 because PA treatment was unable to ameliorate obesity in UCP1 knockout mice. In conclusion, we identified PA as an effective BAT activator that can prevent obesity and may represent a promising strategy for the clinical treatment of obesity and related metabolic diseases. PA treatment effectively and safely protected against obesity via the BAT-UCP1 axis. PA has therapeutic potential for treating obesity and type II diabetes.
棕色脂肪组织（BAT）是适应性产热的主要部位，与能量消耗有关，在肥胖治疗领域受到广泛关注。通过筛选美国食品和药物管理局批准的小分子药物化合物库，发现泛酸能够显著上调解偶联蛋白 1（UCP1）的表达，UCP1 是 BAT 中发现的一种关键产热蛋白。泛酸酯（PA）处理可减少肥胖，逆转肝脏脂肪变性，并通过增加 C57BL/6J 小鼠高脂肪饮食中的能量消耗来改善葡萄糖稳态。PA 还显著增加了 BAT 活性并诱导米色脂肪细胞形成。从机制上讲，这些有益作用是由 UCP1 介导的，因为 PA 处理不能改善 UCP1 敲除小鼠的肥胖。总之，我们确定 PA 是一种有效的 BAT 激活剂，可预防肥胖，可能代表肥胖和相关代谢性疾病临床治疗的有前途的策略。PA 通过 BAT-UCP1 轴有效且安全地预防肥胖。PA 具有治疗肥胖和 II 型糖尿病的潜力。
