cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation心脏微粒体甘油三酸酯转运蛋白的表达增加肥胖和有助于减弱心脏甘油三酯积累.pdfVIP

Cardiac Expression of Microsomal Triglyceride Transfer Protein Is Increased in Obesity and Serves to Attenuate Cardiac Triglyceride Accumulation 1 2 3 4 1,4 Emil D. Bartels , Jan M. Nielsen , Lars I. Hellgren , Thorkil Ploug , Lars B. Nielsen * 1 Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, 2 Department of Cardiology, Aarhus University Hospital, Skejby, Denmark, 3 Department of Systems Biology and Centre for Advanced Food Studies, Technical University of Denmark, Lyngby, Denmark, 4 Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark Abstract Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and b-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism- controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but un