Cardiac lipoprotein lipase activity in the hypertrophied heart may be regulated by fatty acid flux.
Cardiac hypertrophy is characterised by an imbalance between lipid uptake and fatty acid β-oxidation leading to an accumulation of lipids, particularly triacylglycerol (TAG). It is unclear whether uptake mechanisms such as lipoprotein lipase (LPL) can be attenuated to diminish this uptake. Rats were cold acclimated to induce cardiac hypertrophy and increase cardiac LPL. Lipid uptake and metabolism were altered by feeding a 'Western-style' high fat diet (WSD) or feeding oxfenicine (2g/L) in the drinking water. Diastolic stiffness (increased volume change/unit pressure change) was induced in hypertrophied hearts for rats fed WSD (P<0.05) or WSD+oxfenicine (P<0.01), although absolute performance of cardiac muscle, estimated from stress-strain calculations was unchanged. Cold acclimation increased cardiac endothelial LPL (P<0.05) but this was diminished following oxfenicine. Following WSD LPL was further decreased below WSD-fed control hearts (P<0.05) with no further decrease by oxfenicine supplementation. A negative correlation was noted between plasma TAG and endothelial LPL (correlation coefficient=-0.654; P<0.001) but not cardiac TAG concentration. Transcript levels of angiopoietin-like protein-4 (ANGPTL4) were increased 6-fold by WSD (P<0.05) and increased 15-fold following WSD+oxfenicine (P<0.001). For CA-hearts fed WSD or WSD+oxfenicine ANGPTL4 mRNA levels were preserved at chow-fed levels. VLDLR protein levels were increased 10-fold (P<0.01) by CA. ANGPTL4 protein levels were increased 2-fold (P<0.05) by WSD, but restored following oxfenicine. For CA-hearts WSD increased ANGPTL4 protein levels 3-fold (P<0.01) with WSD+oxfenicine increasing ANGPTL4 protein 4-fold (P<0.01). These data suggest that endothelial LPL levels in the heart are altered to maintain FA flux and may exploit ANGPTL4.
School of Clinical and Experimental Medicine, College of Medicinal and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom. d.hauton@bham.ac.uk
David
D
Hauton
Germaine M
GM
Caldwell
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D006332:Cardiomegaly / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D003080:Cold Temperature; D059305:Diet, High-Fat / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D015870:Gene Expression; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D015151:Immunoblotting; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008055:Lipids / Q000032:analysis / Q000097:blood; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
C528241:ANGPTL4 protein, rat; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D008055:Lipids; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor; C023010:4-hydroxyphenylglycine; D008071:Lipoprotein Lipase; D007545:Isoproterenol; D005998:Glycine