Adipocyte triglyceride lipase expression in human obesity

Abstract

We have investigated the gene and protein expression of adipose triglyceride lipase (ATGL) and triglyceride (TG) lipase activity from subcutaneous and visceral adipose tissue of lean and obese subjects. Visceral and subcutaneous adipose tissue was obtained from 16 age-matched lean and obese subjects during abdominal surgery. Tissues were analyzed for mRNA expression of lipolytic enzymes by real-time quantitative PCR. ATGL protein content was assessed by Western blot and TG lipase activity by radiometric assessment. Subcutaneous and visceral adipose tissue of obese subjects had elevated mRNA expression of PNPLA2 (ATGL) and other lipases including PNPLA3, PNPLA4, CES1, and LYPLAL1 (P Ͻ 0.05). Surprisingly, ATGL protein expression and TG lipase activity were reduced in subcutaneous adipose tissue of obese subjects. Immunoprecipitation of ATGL reduced total TG lipase activity in adipose lysates by 70% in obese and 83% in lean subjects. No significant differences in the ATGL activator CGI-58 mRNA levels (ABHD5) were associated with obesity. These data demonstrate that ATGL is important for efficient TG lipase activity in humans. They also demonstrate reduced ATGL protein expression and TG lipase activity despite increased mRNA expression of ATGL and other novel lipolytic enzymes in obesity. The lack of correlation between ATGL protein content and in vitro TG lipase activity indicates that small decrements in ATGL protein expression are not responsible for the reduction in TG lipase activity observed here in obesity, and that posttranslational modifications may be important. triglyceride metabolism; adipose triglyceride lipase; triglyceride hydrolase activity THE ABILITY TO EFFICIENTLY regulate the storage and release of fatty acids contained in adipose triglyceride (TG) requires tight coupling between hydrolysis and esterification. Fat stored in subcutaneous and visceral depots is mobilized by activation of lipolytic enzymes, which degrade TGs and release free fatty acids (FFAs) into the circulation for use as an energy substrate. Obesity is characterized by excessive adipose tissue deposition and increased FFA release that exceeds metabolic demands (17). Elevated postprandial FFAs are a hallmark of obesity (33) and contribute to metabolic disturbances including insulin resistance in skeletal muscle and liver (4, 44), pancreatic ␤-cell dysfunction (51), and increased VLDL triglyceride production (27).Until recently, hormone-sensitive lipase (HSL) was considered the rate-limiting enzyme for lipolysis, but recent evidence suggests that adipose triglyceride lipase (ATGL) may also be important. HSL Ϫ/Ϫ mice have residual TG lipase activity (11, 31, 32) indicative of the presence of other TG lipases and maintain partial basal and catecholamine-stimulated lipolysis (41). Recent studies have identified the molecular lipolytic (and esterolytic) proteome in mouse adipose tissue (3) and 23 proteins that are incompletely characterized. Many of these proteins are predicted to contain an ␣/␤-hydrolase fold that accommodates catal...

Replication Study of 15 Recently Published Loci for Body Fat Distribution in the Japanese Population

“…Although the physiological substrates involved remain unclear, the LYPLAL1 gene may contribute to fat distribution via involvement in lipid and/or glucose metabolism. Indeed, LYPLAL1 mRNA expression is increased in the subcutaneous adipose tissue of obese subjects 24) , but not in their visceral adipose tissue. Previous reports and our results suggest that the LYPLAL1 gene plays a different role in the visceral and subcutaneous adipose tissue mass.…”

Depot-Specific Expression of Lipolytic Genes in Human Adipose Tissues

“…Indeed, cytosolic TG lipase activity in the major omentum was positively correlated with the mRNA expression of PNPLA2 (Table 4), supporting the dominant role of PNPLA2 in the lipolysis of visceral fat. The expression of PNPLA2 protein might not be the sole determinant of PNPLA2-mediated lipolysis, because PNPLA2 is activated by a ubiquitous cofactor, CGI-58 19) ; however, Steinberg et al recently reported the lack of a correlation between PNPLA2 protein content and TG lipase activity 37) . The associations of the mRNA expression of CES1 with clinical parameters of adiposity were more robust than those of PNPLA2 (Table 3).…”

Triacylglycerol lipases and metabolic control: implications for health and disease

“…Similarly, in vivo ATGL overexpression in skeletal muscle (80) or liver (61) reduced TG mass. Finally, immunoinhibition of ATGL in human adipose tissue lysates reduced total TG lipase activity by 70 -83%, indicating an important role for ATGL in human adipocyte lipolysis (71). Aside from its role in TG degradation, Jenkins et al (39) reported acylglycerol transacylase activity of ATGL using an oleate donor, which in the presence of monoolein or diolein produced DG and TG, respectively.…”