Although most mammalian fatty acids (FAs) are straight-chain, there also exist branched-chain FAs such as iso- and anteiso-FAs, especially in the meibomian glands. Meibum lipids, which are secreted from the meibomian glands and are important for dry eye prevention, contain abundant branched-chain lipids, such as cholesteryl esters and wax esters with chain-lengths of ≥C21 (very-long-chain; VLC). However, the exact tissue distribution of branched-chain lipids or the enzymes involved in the production of branched-chain VLCFAs has remained poorly understood. Here, we revealed that FA elongases ELOVL1, ELOVL3, and ELOVL7, of the seven mammalian ELOVL isozymes, elongated saturated branched-chain acyl-CoAs. ELOVL3 was highly active toward iso-C17:0 and anteiso-C17:0 acyl-CoAs and elongated them up to iso-C23:0 and anteiso-C25:0 acyl-CoAs, respectively. ELOVL1 elongated both iso- and anteiso-C23:0 acyl-CoAs to C25:0 acyl-CoAs. By establishing a liquid chromatography-tandem mass spectrometry method capable of separating branched- and straight-chain lipids, we showed that essentially all of the cholesteryl esters and 88% of the wax esters in the mouse meibomian glands are branched. In Elovl1 mutant mice, the levels of ≥C24:0 branched-chain cholesteryl esters and ≥C25:0 branched-chain wax esters were decreased, indicating that ELOVL1 indeed elongates branched-chain VLC acyl-CoAs in vivo. In addition, substantial amounts of ceramides containing branched-chain FAs were present in the skin, meibomian glands, and liver. Our findings provide new insights into the molecular mechanisms that create FA and lipid diversity.

尽管大多数哺乳动物脂肪酸（FAs）是直链的，但也存在支链FAs，例如异脂肪酸和反异脂肪酸，尤其是在睑板腺中。睑板腺分泌的睑板脂质对预防干眼症很重要，它含有丰富的支链脂质，例如胆固醇酯和蜡酯，链长≥C21（超长链； VLC）。然而，对支链脂质或参与生产支链VLCFAs的酶的确切组织分布仍知之甚少。在这里，我们揭示了FA延伸7种哺乳动物ELOVL同工酶中的ELOVL1，ELOVL3和ELOVL7，延长了饱和的支链酰基辅酶A。ELOVL3对iso -C17：0和反异-C17：0酰基-CoA和细长他们最多异-C23：0和反异-C25：0酰基-CoA，分别。ELOVL1细长两个异-和反异-C23：0酰基-CoA至C25：0酰基-CoA。通过建立能够分离支链和直链脂质的液相色谱-串联质谱方法，我们显示了小鼠睑板腺中基本上所有的胆固醇酯和88％的蜡酯都是分支的。在Elovl1突变小鼠中，≥C24：0支链胆固醇酯和≥C25：0支链蜡酯的水平降低，表明ELOVL1实际上在体内延长了支链VLC酰基辅酶A。另外，在皮肤，睑板腺和肝脏中存在大量的含有支链FA的神经酰胺。我们的发现为创建FA和脂质多样性的分子机制提供了新见解。