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.
| Original language | English |
|---|---|
| Pages (from-to) | 1012-1020 |
| Number of pages | 9 |
| Journal | Metabolism: Clinical and Experimental |
| Volume | 60 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2011 |
Bibliographical note
Funding Information:We wish to thank Regina Dennis for assistance with recruitment and the nurses at the General Clinical Research Center for assistance with the procedures. We wish to thank Dr Susan Fried for providing adipose tissue for RNA extraction. Funding: a Merit Review Grant from the Veterans Administration (NR, GR) and grants from the National Institutes of Health ( M01RR14288 , RO1 DK 39176 [PAK], RO1 DK71349 [PAK], and KO1 DK 64716-01 [RHC]). We would also like to acknowledge support from the American Heart Association ( SDA 0335172N [RHC]).
Funding
We wish to thank Regina Dennis for assistance with recruitment and the nurses at the General Clinical Research Center for assistance with the procedures. We wish to thank Dr Susan Fried for providing adipose tissue for RNA extraction. Funding: a Merit Review Grant from the Veterans Administration (NR, GR) and grants from the National Institutes of Health ( M01RR14288 , RO1 DK 39176 [PAK], RO1 DK71349 [PAK], and KO1 DK 64716-01 [RHC]). We would also like to acknowledge support from the American Heart Association ( SDA 0335172N [RHC]).
| Funders | Funder number |
|---|---|
| RHC | |
| Veterans Administration | |
| National Institutes of Health (NIH) | RO1 DK71349, RO1 DK 39176, KO1 DK 64716-01, M01RR14288 |
| National Institutes of Health (NIH) | |
| National Institute of Diabetes and Digestive and Kidney Diseases | K01DK064716 |
| National Institute of Diabetes and Digestive and Kidney Diseases | |
| American the American Heart Association | SDA 0335172N |
| American the American Heart Association |
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrinology
