Hormone-sensitive lipase (HSL) was initially characterized as the hormonally regulated neutral lipase activity responsible for the breakdown of triacylglycerols into fatty acids in adipose tissue. This review aims at providing up-to-date information on structural properties, regulation of expression, activity and function as well as therapeutic potential. The lipase is expressed as different isoforms produced from tissue-specific alternative promoters. All isoforms are composed of an N-terminal domain and a C-terminal catalytic domain within which a regulatory domain containing the phosphorylation sites is embedded. Some isoforms possess additional N-terminal regions. The catalytic domain shares similarities with bacteria, fungus and vascular plant proteins but not with other mammalian lipases. HSL singularity is provided by regulatory and N-terminal domains sharing no homology with other proteins. HSL has a broad substrate specificity compared to other neutral lipases. It hydrolyzes acylglycerols, cholesteryl and retinyl esters among other substrates. A novel role of HSL, independent of its enzymatic function, has recently been described in adipocytes. Clinical studies revealed dysregulations of HSL expression and activity in disorders, such as lipodystrophy, obesity, type 2 diabetes and cancer-associated cachexia. Development of specific inhibitors positions HSL as a pharmacological target for the treatment of metabolic complications.

激素敏感脂肪酶 (HSL) 最初的特征是激素调节的中性脂肪酶活性，负责在脂肪组织中将甘油三酯分解为脂肪酸。本综述旨在提供有关结构特性、表达调控、活性和功能以及治疗潜力的最新信息。脂肪酶表达为由组织特异性替代启动子产生的不同同种型。所有亚型均由 N 端结构域和 C 端催化结构域组成，其中嵌入了包含磷酸化位点的调节结构域。一些同种型具有额外的 N 端区域。催化结构域与细菌、真菌和维管植物蛋白有相似之处，但与其他哺乳动物脂肪酶没有相似之处。HSL 奇点是由与其他蛋白质不具有同源性的调节域和 N 端域提供的。与其他中性脂肪酶相比，HSL 具有广泛的底物特异性。它水解酰基甘油、胆固醇和视黄酯以及其他底物。最近在脂肪细胞中描述了 HSL 的一种新作用，独立于其酶促功能。临床研究揭示了 HSL 表达和活性在脂肪代谢障碍、肥胖症、2 型糖尿病和癌症相关恶病质等疾病中的失调。特异性抑制剂的开发将 HSL 定位为治疗代谢并发症的药理学靶点。胆固醇酯和视黄酯等底物。最近在脂肪细胞中描述了 HSL 的一种新作用，独立于其酶促功能。临床研究揭示了 HSL 表达和活性在脂肪代谢障碍、肥胖症、2 型糖尿病和癌症相关恶病质等疾病中的失调。特异性抑制剂的开发将 HSL 定位为治疗代谢并发症的药理学靶点。胆固醇酯和视黄酯等底物。最近在脂肪细胞中描述了 HSL 的一种新作用，独立于其酶促功能。临床研究揭示了 HSL 表达和活性在脂肪代谢障碍、肥胖症、2 型糖尿病和癌症相关恶病质等疾病中的失调。特异性抑制剂的开发将 HSL 定位为治疗代谢并发症的药理学靶点。