Division of Endocrinology and Metabolism, Diabetes Center, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
J Atheroscler Thromb. 2011;18(3):190-9. doi: 10.5551/jat.6478. Epub 2010 Nov 11.
Adipocyte lipolysis is mediated by a family of triglyceride (TG) lipases consisting of hormone-sensitive lipase (LIPE), adipose triglyceride lipase (PNPLA2) and carboxylesterase 1 (CES1); however, little is known about the relationship between the expression of each gene in different depots and TG lipase activity or obesity.
We measured both mRNA expression levels of the lipolytic enzymes (LIPE, PNPLA2 and CES1) and TG lipase activities of biopsy samples obtained from subcutaneous, omental and mesenteric adipose tissues of 34 patients who underwent abdominal surgery. The results were correlated with clinical parameters: adiposity measures, parameters for insulin resistance and plasma lipid levels.
PNPLA2 mRNA levels were slightly higher in omental fat than subcutaneous fat. Cytosolic TG lipase activities were positively correlated with the mRNA levels of CES1 in subcutaneous fat and mesenteric fat, while they were correlated with those of PNPLA2 in omental fat. The mRNA levels of LIPE were negatively correlated with various measures of adiposity in subcutaneous fat. The mRNA levels of CES1 were positively correlated with various measures of adiposity, particularly those estimated by CT in the three depots; they were also positively correlated with plasma LDL-cholesterol levels in omental fat. In contrast, the mRNA levels of PNPLA2 were not significantly associated with adiposity.
The positive correlations of the expression of CES1 with cytosolic TG lipase activities as well as with adiposity suggest that CES1 is involved in lipolysis, thereby contributing to the development of obesity-associated phenotypes. On the other hand, the expression of LIPE is negatively correlated with adiposity. These distinct regulatory patterns of lipolytic genes may underlie the complex phenotypes associated with human obesity.
脂肪细胞的脂解作用是由一组甘油三酯(TG)脂肪酶介导的,包括激素敏感脂肪酶(LIPE)、脂肪甘油三酯脂肪酶(PNPLA2)和羧酸酯酶 1(CES1);然而,对于不同部位每个基因的表达与 TG 脂肪酶活性或肥胖之间的关系知之甚少。
我们测量了 34 例接受腹部手术的患者皮下、网膜和肠系膜脂肪活检样本中脂解酶(LIPE、PNPLA2 和 CES1)的 mRNA 表达水平和 TG 脂肪酶活性,并将结果与临床参数相关联:肥胖测量指标、胰岛素抵抗参数和血浆脂质水平。
网膜脂肪中的 PNPLA2 mRNA 水平略高于皮下脂肪。细胞溶质 TG 脂肪酶活性与皮下脂肪和肠系膜脂肪中 CES1 的 mRNA 水平呈正相关,而与网膜脂肪中 PNPLA2 的 mRNA 水平呈正相关。LIPE 的 mRNA 水平与皮下脂肪中各种肥胖指标呈负相关。CES1 的 mRNA 水平与皮下脂肪中各种肥胖指标呈正相关,尤其是三个部位的 CT 估计值;它们也与网膜脂肪中的血浆 LDL 胆固醇水平呈正相关。相比之下,PNPLA2 的 mRNA 水平与肥胖症无显著相关性。
CES1 的表达与细胞溶质 TG 脂肪酶活性以及肥胖呈正相关,提示 CES1 参与脂解作用,从而有助于肥胖相关表型的发展。另一方面,LIPE 的表达与肥胖呈负相关。这些不同的脂解基因调控模式可能是人类肥胖相关表型的基础。