Ray Hind, Beylot Michel, Arner Peter, Larrouy Dominique, Langin Dominique, Holm Cecilia, Large Valérie
Institut National de la Santé et de la Recherche Medicale (INSERM) 499, Faculté de Médecine Laennec, Rue Paradin, 69372 Lyon, France.
Diabetes. 2003 Jun;52(6):1417-22. doi: 10.2337/diabetes.52.6.1417.
Hormone-sensitive lipase (HSL)-L is a key enzyme in the mobilization of fatty acids from triglyceride stores in adipocytes. A shorter variant of HSL (HSL-S) was detected in humans. This one is generated through in-frame skipping of exon 6 during the processing of HSL mRNA and results in a protein devoid of lipase activity. The role of HSL-S is unknown. The aims of this study were to identify both HSL variants in adipose tissue biopsies and to determine if the presence of HSL-S is correlated to the lipolytic capacity of adipocytes. The study was performed in human abdominal subcutaneous adipocytes from two groups of seven obese subjects. In the group of subjects with both HSL proteins (L+S) group, two immunoreactive bands (80 and 88 kDa) were detected, whereas only the 88-kDa protein was detected in the group with only the wild-type HSL-protein (L group). In the L+S group, the HSL activity was 20% lower (P < 0.05) and the (S/S(+)) HSL mRNA ratio was twofold higher than in the L group (P < 0.05). The maximally lipolytic capacities measured from isolated adipocytes incubated with norepinephrine or other lipolytic agents were 40% lower in the L+S group (P < 0.05). These results suggest that the presence of the truncated HSL protein is associated with an impaired adipocyte lipolysis.
激素敏感性脂肪酶（HSL）-L是脂肪细胞中甘油三酯储存的脂肪酸动员的关键酶。在人类中检测到一种较短的HSL变体（HSL-S）。它是通过HSL mRNA加工过程中外显子6的框内跳跃产生的，导致产生一种缺乏脂肪酶活性的蛋白质。HSL-S的作用尚不清楚。本研究的目的是在脂肪组织活检中鉴定两种HSL变体，并确定HSL-S的存在是否与脂肪细胞的脂解能力相关。该研究在两组各7名肥胖受试者的腹部皮下脂肪细胞中进行。在同时含有两种HSL蛋白（L+S）的受试者组中，检测到两条免疫反应带（80和88 kDa），而在仅含有野生型HSL蛋白的组（L组）中仅检测到88 kDa的蛋白。在L+S组中，HSL活性降低20%（P<0.05），且（S/S(+)）HSL mRNA比值比L组高两倍（P<0.05）。用去甲肾上腺素或其他脂解剂孵育分离的脂肪细胞测得的最大脂解能力在L+S组中降低40%（P<0.05）。这些结果表明，截短的HSL蛋白的存在与脂肪细胞脂解受损有关。
