Effect of 3,5-diiodo-l-thyronine (T2) and 3,3',5'- triiodo-l-thyronine (T3) on the lipogenic and lipolytic enzymes expression in white adipose tissue of obese mice

Abstract

Thyroid hormones play a recognized and powerful lipolytic and lipogenic effect in White Adipose Tissue (WAT), however little is known about the molecular mechanisms involved in these actions. It is known that the main effectors of the lipolytic action in this tissue are the enzymes: hormone sensitive lipase (HSL) and the specific triglyceride lipase of adipocytes (ATGL), which hydrolyze triglycerides into fatty acids and glycerol. Other components involved in lipase activity are perilipins, which involve the fat droplet, forming a protective barrier against HSL and ATGL action. Other iodothyronines, such as 3,5-diiodo-L-thyronine or T2, have important biological effects on metabolism, but little is known about their actions on white adipose tissue. Considering: (a) the importance of adipose tissue in energy homeostasis and as a source of cytokines, which straightly correlate to tissue sensitivity to insulin, (b) that T2 presents a thyromimetic activity and (c) that the lipolytic and lipogenic actions of T2 and T3, which are important regulators of energy homeostasis, have been poorly explored, we intend to investigate in obese mice whether: (a) T2 and T3 interfere with the expression of the hormone sensitive lipase (HSL), adipocyte triglyceride lipase (ATGL) and perilipin, and (b) T2 regulates the expression of lipogenic enzymes acyltransferase glycerol-3-phosphate (GPAT) and fatty acid synthetase (FAS) in periepidimal white adipose tissue. The results obtained could enlarge our understanding about the contribution of these hormones in obesity-related complications, and provide information on the possible therapeutic benefits of T2, since thyroid hormones nuclear receptors (THRs) present very low affinity for T2, which indicates that putatively it might not induce thyrotoxicosis. (AU)