1. Absence of cardiac lipid accumulation in transgenic mice with heart-specific HSL overexpression
- Author
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SUZUKI, JINYA, SHEN, WEN-JUN, NELSON, BRETT D., PATEL, SHAILJA, VEERKAMP, JACQUES H., SELWOOD, SIMON P., MURPHY, GREER M., JR., REAVEN, EVE, and KRAEMER, FREDRIC B.
- Subjects
Gene expression -- Analysis ,Adipose tissues -- Physiological aspects ,Biological sciences - Abstract
Hormone-sensitive lipase (HSL) hydrolyzes triglyceride (TG) in adipose tissue. HSL is also expressed in heart. To explore the actions of cardiac HSL, heart-specific, tetracycline (Tc)-controlled HSL-overexpressing mice were generated. 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-HSL) were maintained with doxycycline (Dox) to suppress Tg HSL. Upon removal of Dox, cardiac HSL activity and protein increased 12- and 8-fold, respectively, and the expression was heart specific. Although cardiac TG content increased twofold in control mice after an overnight fast, it did not increase in HSL-induced mice. Electron microscopy showed numerous lipid droplets in the myocardium of fasted control mice, whereas fasted HSL-induced mice showed 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-induced mice. Thus cardiac HSL plays a role in controlling accumulation of triglyceride droplets and can affect the expression of a number of cardiac genes. hormone-sensitive lipase; gene expression; microarray analysis
- Published
- 2001