Adipose triglyceride lipase expression in human adipose tissue and muscle. Role in insulin resistance and response to training and pioglitazone

Abstract

Adipose triglyceride lipase (ATGL) catalyzes the first step in adipocyte and muscle triglyceride hydrolysis, and comparative gene identification–58 (CGI-58) is an essential cofactor. We studied the expression of ATGL and CGI-58 in human adipose and muscle and examined correlations with markers of muscle fatty acid oxidation. Nondiabetic volunteers were studied. Subjects with impaired glucose tolerance were treated with pioglitazone or metformin for 10 weeks. Subjects with normal glucose tolerance underwent a 12-week training program. We examined changes in ATGL and CGI-58 with obesity and insulin resistance, and effects of exercise and pioglitazone. Adipose triglyceride lipase messenger RNA (mRNA) expression showed no correlation with either body mass index or insulin sensitivity index in either adipose or muscle. However, adipose ATGL protein levels were inversely correlated with body mass index ( r = −0.64, P < .02) and positively correlated with insulin sensitivity index ( r = 0.67, P < .02). In muscle, ATGL mRNA demonstrated a strong positive relationship with carnitine palmitoyltransferase I mRNA ( r = 0.82, P < .0001) and the adiponectin receptors AdipoR1 mRNA ( r = 0.71, P < .0001) and AdipoR2 mRNA ( r = 0.74, P < .0001). Muscle CGI-58 mRNA was inversely correlated with intramyocellular triglyceride in both type 1 ( r = −0.35, P < .05) and type 2 ( r = −0.40, P < .05) fibers. Exercise training resulted in increased muscle ATGL, and pioglitazone increased adipose ATGL by 31% ( P < .05). Pioglitazone also increased ATGL in adipocytes. Adipose ATGL protein is decreased with insulin resistance and obesity; and muscle ATGL mRNA is associated with markers of fatty acid oxidation in muscle, as is CGI-58. The regulation of ATGL and CGI-58 has important implications for the control of lipotoxicity.