Jocken Johan W E, Langin Dominique, Smit Egbert, Saris Wim H M, Valle Carine, Hul Gabby B, Holm Cecilia, Arner Peter, Blaak Ellen E
Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
J Clin Endocrinol Metab. 2007 Jun;92(6):2292-9. doi: 10.1210/jc.2006-1318. Epub 2007 Mar 13.
AIM/HYPOTHESIS: Obesity is associated with increased triacylglycerol (TAG) storage in adipose tissue and insulin resistance. The mobilization of stored TAG is mediated by hormone-sensitive lipase (HSL) and the recently discovered adipose triglyceride lipase (ATGL). The aim of the present study was to examine whether ATGL and HSL mRNA and protein expression are altered in insulin-resistant conditions. In addition, we investigated whether a possible impaired expression could be reversed by a period of weight reduction.
Adipose tissue biopsies were taken from obese subjects (n = 44) with a wide range of insulin resistance, before and just after a 10-wk hypocaloric diet. ATGL and HSL protein and mRNA expression was determined by Western blot and quantitative RT-PCR, respectively.
Fasting insulin levels and the degree of insulin resistance (using the homeostasis model assessment index for insulin resistance) were negatively correlated with ATGL and HSL protein expression, independent of age, gender, fat cell size, and body composition. Both mRNA and protein levels of ATGL and HSL were reduced in insulin-resistant compared with insulin-sensitive subjects (P < 0.05). Weight reduction significantly decreased ATGL and HSL mRNA and protein expression. A positive correlation between the decrease in leptin and the decrease in ATGL protein level after weight reduction was observed. Finally, ATGL and HSL mRNA and protein levels seem to be highly correlated, indicating a tight coregulation and transcriptional control.
In obese subjects, insulin resistance and hyperinsulinemia are strongly associated with ATGL and HSL mRNA and protein expression, independent of fat mass. Data on weight reduction indicated that also other factors (e.g. leptin) relate to ATGL and HSL protein expression.
目的/假设：肥胖与脂肪组织中三酰甘油（TAG）储存增加及胰岛素抵抗相关。储存的TAG的动员由激素敏感性脂肪酶（HSL）和最近发现的脂肪甘油三酯脂肪酶（ATGL）介导。本研究的目的是检查在胰岛素抵抗状态下ATGL和HSL的mRNA及蛋白表达是否发生改变。此外，我们研究了一段时间的体重减轻是否可以逆转可能存在的表达受损情况。
从具有广泛胰岛素抵抗的肥胖受试者（n = 44）中获取脂肪组织活检样本，分别在10周低热量饮食之前和之后。通过蛋白质印迹法和定量逆转录聚合酶链反应分别测定ATGL和HSL的蛋白及mRNA表达。
空腹胰岛素水平和胰岛素抵抗程度（使用胰岛素抵抗的稳态模型评估指数）与ATGL和HSL蛋白表达呈负相关，与年龄、性别、脂肪细胞大小和身体组成无关。与胰岛素敏感的受试者相比，胰岛素抵抗受试者中ATGL和HSL的mRNA及蛋白水平均降低（P < 0.05）。体重减轻显著降低了ATGL和HSL的mRNA及蛋白表达。观察到体重减轻后瘦素降低与ATGL蛋白水平降低之间存在正相关。最后，ATGL和HSL的mRNA及蛋白水平似乎高度相关，表明存在紧密的共同调节和转录控制。
在肥胖受试者中，胰岛素抵抗和高胰岛素血症与ATGL和HSL的mRNA及蛋白表达密切相关，与脂肪量无关。体重减轻的数据表明，其他因素（如瘦素）也与ATGL和HSL蛋白表达有关。
