Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Division of Medical Genetics, Department of Pediatrics, Université de Montréal and CHU Sainte-Justine, 3175 Côte Sainte-Catherine, Montreal, QC H3T 1C5, Canada.
Cells. 2019 Apr 29;8(5):395. doi: 10.3390/cells8050395.
White adipose tissue (WAT) lipolysis contributes to energy balance during fasting. Lipolysis can proceed by the sequential hydrolysis of triglycerides (TGs) by adipose triglyceride lipase (ATGL), then of diacylglycerols (DGs) by hormone-sensitive lipase (HSL). We showed that the combined genetic deficiency of ATGL and HSL in mouse adipose tissue produces a striking different phenotype from that of isolated ATGL deficiency, inconsistent with the linear model of lipolysis. We hypothesized that the mechanism might be functional redundancy between ATGL and HSL. To test this, the TG hydrolase activity of HSL was measured in WAT. HSL showed TG hydrolase activity. Then, to test ATGL for activity towards DGs, radiolabeled DGs were incubated with HSL-deficient lipid droplet fractions. The content of TG increased, suggesting DG-to-TG synthesis rather than DG hydrolysis. TG synthesis was abolished by a specific ATGL inhibitor, suggesting that ATGL functions as a transacylase when HSL is deficient, transferring an acyl group from one DG to another, forming a TG plus a monoglyceride (MG) that could be hydrolyzed by monoglyceride lipase. These results reveal a previously unknown physiological redundancy between ATGL and HSL, a mechanism for the epistatic interaction between and . It provides an alternative lipolytic pathway, potentially important in patients with deficient lipolysis.
白色脂肪组织 (WAT) 的脂肪分解有助于禁食期间的能量平衡。脂肪分解可以通过脂肪甘油三酯脂肪酶 (ATGL) 对甘油三酯 (TGs) 的顺序水解，然后通过激素敏感脂肪酶 (HSL) 对二酰基甘油 (DGs) 的水解来进行。我们表明，在小鼠脂肪组织中联合遗传缺乏 ATGL 和 HSL 会产生与单独缺乏 ATGL 截然不同的表型，与脂肪分解的线性模型不一致。我们假设其机制可能是 ATGL 和 HSL 之间的功能冗余。为了验证这一点，我们测量了 HSL 在 WAT 中的 TG 水解酶活性。HSL 显示出 TG 水解酶活性。然后，为了测试 ATGL 对 DGs 的活性，用 HSL 缺陷的脂滴级分孵育放射性标记的 DGs。TG 的含量增加，表明发生了从 DG 到 TG 的合成而不是 DG 的水解。特定的 ATGL 抑制剂消除了 TG 合成，表明当 HSL 缺乏时，ATGL 作为转酰基酶起作用，将酰基从一个 DG 转移到另一个 DG，形成 TG 和单甘油酯 (MG)，后者可被单甘油酯脂肪酶水解。这些结果揭示了 ATGL 和 HSL 之间以前未知的生理冗余，这是 和 之间上位性相互作用的机制。它提供了一种替代的脂肪分解途径，可能对脂肪分解不足的患者很重要。
