Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, USA.
Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, USA.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Jan;1864(1):79-90. doi: 10.1016/j.bbalip.2018.05.008. Epub 2018 May 21.
Channeling carbohydrates and fatty acids to thermogenic tissues, including brown and beige adipocytes, have garnered interest as an approach for the management of obesity-related metabolic disorders. Mitochondrial fatty acid oxidation (β-oxidation) is crucial for the maintenance of thermogenesis. Upon cellular fatty acid uptake or following lipolysis from triglycerides (TG), fatty acids are esterified to coenzyme A (CoA) to form active acyl-CoA molecules. This enzymatic reaction is essential for their utilization in β-oxidation and thermogenesis. The activation and deactivation of fatty acids are regulated by two sets of enzymes called acyl-CoA synthetases (ACS) and acyl-CoA thioesterases (ACOT), respectively. The expression levels of ACS and ACOT family members in thermogenic tissues will determine the substrate availability for β-oxidation, and consequently the thermogenic capacity. Although the role of the majority of ACS and ACOT family members in thermogenesis remains unclear, recent proceedings link the enzymatic activities of ACS and ACOT family members to metabolic disorders and thermogenesis. Elucidating the contributions of specific ACS and ACOT family members to trafficking of fatty acids towards thermogenesis may reveal novel targets for modulating thermogenic capacity and treating metabolic disorders.
将碳水化合物和脂肪酸导向产热组织，包括棕色和米色脂肪细胞，已成为治疗肥胖相关代谢紊乱的一种方法。线粒体脂肪酸氧化（β-氧化）对于维持产热至关重要。在细胞脂肪酸摄取后或甘油三酯（TG）分解后，脂肪酸被酯化到辅酶 A（CoA）上形成活性酰基辅酶 A 分子。这个酶促反应对于它们在β-氧化和产热中的利用是必不可少的。脂肪酸的激活和失活分别由两组称为酰基辅酶 A 合成酶（ACS）和酰基辅酶 A 硫酯酶（ACOT）的酶来调节。在产热组织中，ACS 和 ACOT 家族成员的表达水平将决定β-氧化的底物可用性，从而决定产热能力。尽管大多数 ACS 和 ACOT 家族成员在产热中的作用仍不清楚，但最近的研究结果将 ACS 和 ACOT 家族成员的酶活性与代谢紊乱和产热联系起来。阐明特定 ACS 和 ACOT 家族成员在脂肪酸向产热的运输中的作用可能揭示调节产热能力和治疗代谢紊乱的新靶点。
