Prolonged exposure to high dietary lipids is not associated with lipotoxicity in heart failure.
Previous studies have reported that elevated myocardial lipids in a model of mild-to-moderate heart failure increased mitochondrial function, but did not alter left ventricular function. Whether more prolonged exposure to high dietary lipids would promote a lipotoxic phenotype in mitochondrial and myocardial contractile function has not been determined. We tested the hypothesis that prolonged exposure to high dietary lipids, following coronary artery ligation, would preserve myocardial and mitochondrial function in heart failure. Rats underwent ligation or sham surgery and were fed normal (10% kcal fat) (SHAM, HF) or high fat diet (60% kcal saturated fat) (SHAM+FAT, HF+FAT) for sixteen weeks. Although high dietary fat was accompanied by myocardial tissue triglyceride accumulation (SHAM 1.47+/-0.14; SHAM+FAT 2.32+/-0.14; HF 1.34+/-0.14; HF+FAT 2.21+/-0.20 micromol/gww), fractional shortening was increased 16% in SHAM+FAT and 28% in HF+FAT compared to SHAM and HF, respectively. Despite increased medium-chain acyl-CoA dehydrogenase (MCAD) activity in interfibrillar mitochondria (IFM) of both SHAM+FAT and HF+FAT, dietary lipids also were associated with decreased state 3 respiration using palmitoylcarnitine (SHAM 369+/-14; SHAM+FAT 307+/-23; HF 354+/-13; HF+FAT 366+/-18 nAO min(-1) mg(-1)) in SHAM+FAT compared to SHAM and HF+FAT. State 3 respiration in IFM also was decreased in SHAM+FAT relative to SHAM using succinate and DHQ. In conclusion, high dietary lipids promoted myocardial lipid accumulation, but were not accompanied by alterations in myocardial contractile function typically associated with lipotoxicity. In normal animals, high dietary fat decreased mitochondrial respiration, but also increased MCAD activity. These studies support the concept that high fat feeding can modify multiple cellular pathways that differentially affect mitochondrial function under normal and pathological conditions.
Rennison
Julie H
JH
Department of Physiology and Biophysics, School of Medicine E558, Case Western Reserve University, Cleveland, OH 44106-4970, USA.
McElfresh
Tracy A
TA
Chen
Xiaoqin
X
Anand
Vijay R
VR
Hoit
Brian D
BD
Hoppel
Charles L
CL
Chandler
Margaret P
MP
D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D044926:Butyryl-CoA Dehydrogenase; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D052242:Adiponectin; D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D024101:Mitochondrial Proteins; D044926:Butyryl-CoA Dehydrogenase; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain