Cardiac-specific knock-out of lipoprotein lipase alters plasma lipoprotein triglyceride metabolism and cardiac gene expression.
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.
Augustus
Ayanna
A
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Yagyu
Hiroaki
H
Haemmerle
Guenter
G
Bensadoun
André
A
Vikramadithyan
Reeba K
RK
Park
So-Young
SY
Kim
Jason K
JK
Zechner
Rudolf
R
Goldberg
Ira J
IJ
D000818:Animals; D015152:Blotting, Northern; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4; D008071:Lipoprotein Lipase / Q000235:genetics / Q000502:physiology*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000502:physiology; D009124:Muscle Proteins; D009206:Myocardium / Q000201:enzymology*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D008074:Lipoproteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; D014280:Triglycerides; C030087:lipoprotein triglyceride; D008071:Lipoprotein Lipase