Absence of cardiac lipid accumulation in transgenic mice with heart-specific HSL overexpression.
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.
Suzuki
J
J
Division of Endocrinology, Stanford University, Stanford 94305, USA.
Shen
W J
WJ
Nelson
B D
BD
Patel
S
S
Veerkamp
J H
JH
Selwood
S P
SP
Murphy
G M
GM
Reaven
E
E
Kraemer
F B
FB
D000818:Animals; D003433:Crosses, Genetic; D017931:DNA Primers; D004318:Doxycycline / Q000494:pharmacology; D004435:Eating; D004790:Enzyme Induction; D005215:Fasting; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D006352:Heart Ventricles; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D018995:Myosin Heavy Chains / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013154:Spleen / Q000201:enzymology; D002787:Sterol Esterase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D013737:Testis / Q000201:enzymology; D015534:Trans-Activators / Q000235:genetics
D017931:DNA Primers; D008055:Lipids; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D002787:Sterol Esterase; D018995:Myosin Heavy Chains; D004318:Doxycycline