Absence of cardiac lipid accumulation in transgenic mice with heart-specific HSL overexpression

Hormone-sensitive lipase (HSL) hydrolyzes triglyceride (TG) in adipose tiss ue. HSL is also expressed in heart. To explore the actions of cardiac HSL, heart-specific, tetracycline (Tc)-controlled HSL-overexpressing mice were g enerated. Tc-responsive element-HSL transgenic (Tg) mice were generated and crossed with myosin heavy chain (MHC)alpha -tTA Tg mice, which express the Tc-responsive transactivator (tTA) in the heart. The double-Tg mice (MHC-H SL) were maintained with doxycycline (Dox) to suppress Tg HSL. Upon removal of Dox, cardiac HSL activity and protein increased 12- and 8-fold, respect ively, and the expression was heart specific. Although cardiac TG content i ncreased twofold in control mice after an overnight fast, it did not increa se in HSL-induced mice. Electron microscopy showed numerous lipid droplets in the myocardium of fasted control mice, whereas fasted HSL-induced mice s howed virtually no droplets. Microarray analysis showed altered expression of cardiac genes for fatty acid oxidation, transcription factors, signaling molecules, cytoskeletal proteins, and histocompatibility antigens in HSL-i nduced mice. Thus cardiac HSL plays a role in controlling accumulation of t riglyceride droplets and can affect the expression of a number of cardiac g enes.