Rajakumari Sona, Srivastava Simran
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru 560012, India.
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru 560012, India.
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Jul;1866(7):158922. doi: 10.1016/j.bbalip.2021.158922. Epub 2021 Mar 11.
Mitochondrial abundance and thermogenic capacity are two imperative components that distinguish brown, beige and white adipose tissues. Most importantly, the lipid composition is vital for maintaining the quantity, quality and function of mitochondria. Therefore, we employed quantitative lipidomics to probe the mitochondrial lipidome of adipose tissues. The mitochondrial lipidome reveals β3-adrenergic stimulation and aging drastically altered the levels of phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio and acyl chain desaturation. Precisely, PC and PE levels correlate with the increased brown and beige fat activity in young mice. While aging increased lysoPC species in white adipose tissue (WAT) mitochondria, CL-316,243 administration reduced lysoPC species and increased lyso-PE content during WAT browning. Also, non-thermogenic mitochondria accumulate sphingomyelin (SM), phosphatidylserine (PS), phosphatidic acid (PA) and ether-linked PC (ePC). Similarly, enrichment of phosphatidylglycerol (PG) and cardiolipin (CL) levels are associated with thermogenic mitochondria. Also, our in vitro experiment supports that blocking the de novo sphingolipid synthesis pathway by myriocin, SPT1 inhibitor increased the thermogenic capacity and oxygen consumption rate in mature adipocytes. Overall, our study suggests mitochondria of brown, beige and white adipose tissues own a unique pattern of lipid molecular species and their levels are altered by aging and CL-316,243 administration.
线粒体丰度和产热能力是区分棕色、米色和白色脂肪组织的两个重要组成部分。最重要的是，脂质组成对于维持线粒体的数量、质量和功能至关重要。因此，我们采用定量脂质组学来探究脂肪组织的线粒体脂质组。线粒体脂质组显示，β3-肾上腺素能刺激和衰老极大地改变了磷脂酰胆碱（PC）/磷脂酰乙醇胺（PE）的比例水平以及酰基链去饱和作用。确切地说，PC和PE水平与年轻小鼠棕色和米色脂肪活性的增加相关。衰老会增加白色脂肪组织（WAT）线粒体中的溶血磷脂酰胆碱（lysoPC）种类，而给予CL-316,243会减少WAT线粒体中的lysoPC种类并增加溶血磷脂酰乙醇胺（lyso-PE）含量。此外，非产热线粒体积累鞘磷脂（SM）、磷脂酰丝氨酸（PS）、磷脂酸（PA）和醚连接的PC（ePC）。同样，磷脂酰甘油（PG）和心磷脂（CL）水平的富集与产热线粒体相关。而且，我们的体外实验支持，通过肌醇六磷酸（myriocin）（一种SPT1抑制剂）阻断从头鞘脂合成途径可提高成熟脂肪细胞的产热能力和氧消耗率。总体而言，我们的研究表明，棕色、米色和白色脂肪组织的线粒体具有独特的脂质分子种类模式，并且它们的水平会因衰老和给予CL-316,243而改变。
