Tan Chong Yew, Virtue Samuel, Bidault Guillaume, Dale Martin, Hagen Rachel, Griffin Julian L, Vidal-Puig Antonio
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Cell Rep. 2015 Dec 15;13(10):2039-47. doi: 10.1016/j.celrep.2015.11.004. Epub 2015 Nov 25.
Although many transcriptional pathways regulating BAT have been identified, the role of lipid biosynthetic enzymes in thermogenesis has been less investigated. Whereas cold exposure causes changes in the fatty acid composition of BAT, the functional consequences of this remains relatively unexplored. In this study, we demonstrate that the enzyme Elongation of Very Long Chain fatty acids 6 (Elovl6) is necessary for the thermogenic action of BAT. Elovl6 is responsible for converting C16 non-essential fatty acids into C18 species. Loss of Elovl6 does not modulate traditional BAT markers; instead, it causes reduced expression of mitochondrial electron transport chain components and lower BAT thermogenic capacity. The reduction in BAT activity appears to be counteracted by increased beiging of scWAT. When beige fat is disabled by thermoneutrality or aging, Elovl6 KO mice gain weight and have increased scWAT mass and impaired carbohydrate metabolism. Overall, our study suggests fatty acid chain length is important for BAT function.
尽管已经确定了许多调节褐色脂肪组织(BAT)的转录途径,但脂质生物合成酶在产热中的作用却较少被研究。虽然冷暴露会导致BAT脂肪酸组成发生变化,但其功能后果仍相对未被探索。在本研究中,我们证明超长链脂肪酸延长酶6(Elovl6)对于BAT的产热作用是必需的。Elovl6负责将C16非必需脂肪酸转化为C18脂肪酸。Elovl6的缺失不会调节传统的BAT标志物;相反,它会导致线粒体电子传递链成分的表达降低以及BAT产热能力下降。BAT活性的降低似乎被皮下白色脂肪组织(scWAT)米色化增加所抵消。当通过热中性或衰老使米色脂肪失活时,Elovl6基因敲除小鼠体重增加,scWAT质量增加,碳水化合物代谢受损。总体而言,我们的研究表明脂肪酸链长度对BAT功能很重要。