We previously discovered in mouse adipocytes an lncRNA (the homolog of human LINC00116) regulating adipogenesis that contains a highly conserved coding region. Here, we show human protein expression of a peptide within LINC00116, and demonstrate that this peptide modulates triglyceride clearance in human adipocytes by regulating lipolysis and mitochondrial β-oxidation. This gene has previously been identified as mitoregulin (MTLN). We conclude that MTLN has a regulatory role in adipocyte metabolism as demonstrated by systemic lipid phenotypes in knockout mice. We also assert its adipocyte-autonomous phenotypes in both isolated murine adipocytes as well as human stem cell-derived adipocytes. MTLN directly interacts with the β subunit of the mitochondrial trifunctional protein, an enzyme critical in the β-oxidation of long-chain fatty acids. Our human and murine models contend that MTLN could be an avenue for further therapeutic research, albeit not without caveats, for example, by promoting white adipocyte triglyceride clearance in obese subjects.

我们先前在小鼠脂肪细胞中发现了一个lncRNA（人类LINC00116的同系物），它调控着脂肪形成，其中包含一个高度保守的编码区。在这里，我们显示了LINC00116中某肽的人类蛋白表达，并证明了该肽通过调节脂解作用和线粒体β-氧化作用来调节人脂肪细胞中的甘油三酸酯清除率。该基因先前已被鉴定为线粒调节蛋白（MTLN）。我们得出的结论是，MTLN在脂肪细胞代谢中具有调节作用，如基因敲除小鼠中的系统脂质表型所证明。我们还断言它在分离的鼠类脂肪细胞以及人类干细胞衍生的脂肪细胞中的脂肪细胞自主表型。顶级域名与线粒体三功能蛋白的β亚基直接相互作用，后者是长链脂肪酸β氧化的关键酶。我们的人类和鼠类模型认为MTLN可能是进一步治疗研究的途径，尽管并非没有警告，例如，通过促进肥胖受试者中白色脂肪细胞甘油三酸酯的清除。