Cardiac-specific knock-out of lipoprotein lipase alters plasma lipoprotein triglyceride metabolism and cardiac gene expression. Journal   The Journal of biological chemistry. Citation   J Biol Chem. 279(24):25050-7 Publication date   2004 Jun 11 Authors   Augustus A Yagyu H Haemmerle G Bensadoun A Vikramadithyan RK Park SY Kim JK Zechner R Goldberg IJ Investigators   Jason K. Kim Grant agencies   National Heart, Lung, and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases Grants   NHLBI HL073029 NHLBI HL45095 NIDDK U24 DK59635 MeSH headings   Lipoprotein Lipase Lipoproteins Muscle Proteins Myocardium Triglycerides MeSH qualifiers   physiology metabolism enzymology Abstract   Fatty acids are the primary energy source for the heart. The heart acquires fatty acids associated with albumin or derived from lipoprotein lipase (LpL)-mediated hydrolysis of lipoprotein triglyceride (TG). We generated heart-specific LpL knock-out mice (hLpL0) to determine whether cardiac LpL modulates the actions of peroxisome proliferator-activated receptors and affects whole body lipid metabolism. Male hLpL0 mice had significantly elevated plasma TG levels and decreased clearance of postprandial lipids despite normal postheparin plasma LpL activity. Very large density lipoprotein-TG uptake was decreased by 72% in hLpL0 hearts. However, heart uptake of albumin-bound free fatty acids was not altered. Northern blot analysis revealed a decrease in the expression of peroxisome proliferator-activated receptor alpha-response genes involved in fatty acid beta-oxidation. Surprisingly, the expression of glucose transporters 1 and 4 and insulin receptor substrate 2 was increased and that of pyruvate dehydrogenase kinase 4 and insulin receptor substrate 1 was reduced. Basal glucose uptake was increased markedly in hLpL0 hearts. Thus, the loss of LpL in the heart leads to defective plasma metabolism of TG. Moreover, fatty acids derived from lipoprotein TG and not just albumin-associated fatty acids are important for cardiac lipid metabolism and gene regulation.