Enhanced acyl-CoA dehydrogenase activity is associated with improved mitochondrial and contractile function in heart failure.

Abstract

AIMS:

Heart failure is associated with decreased myocardial fatty acid oxidation capacity and has been likened to energy starvation. Increased fatty acid availability results in an induction of genes promoting fatty acid oxidation. The aim of the present study was to investigate possible mechanisms by which high fat feeding improved mitochondrial and contractile function in heart failure.

METHODS AND RESULTS:

Male Wistar rats underwent coronary artery ligation (HF) or sham surgery and were immediately fed either a normal (14% kcal fat) (SHAM, HF) or high-fat diet (60% kcal saturated fat) (SHAM+FAT, HF+FAT) for 8 weeks. Mitochondrial respiration and gene expression and enzyme activities of fatty acid-regulated mitochondrial genes and proteins were assessed. Subsarcolemmal (SSM) and interfibrillar mitochondria were isolated from the left ventricle. State 3 respiration using lipid substrates octanoylcarnitine and palmitoylcarnitine increased in the SSM of HF+FAT compared with SHAM+FAT and HF, respectively (242 +/- 21, 246 +/- 21 vs. 183 +/- 8, 181 +/- 6 and 193 +/- 17, 185 +/- 16 nAO min(-1) mg(-1)). Despite decreased medium-chain acyl-CoA dehydrogenase (MCAD) mRNA in HF and HF+FAT, MCAD protein was not altered, and MCAD activity increased in HF+FAT (HF, 65.1 +/- 2.7 vs. HF+FAT, 81.5 +/- 5.4 nmoles min(-1) mg(-1)). Activities of short- and long-chain acyl-CoA dehydrogenase also were elevated and correlated to increased state 3 respiration. This was associated with an improvement in myocardial contractility as assessed by left ventricular +dP/dt max.

CONCLUSION:

Administration of a high-fat diet increased state 3 respiration and acyl-CoA dehydrogenase activities, but did not normalize mRNA or protein levels of acyl-CoA dehydrogenases in coronary artery ligation-induced heart failure rats.

• Authors: Julie H Rennison, Tracy A McElfresh, Isidore C Okere, Hiral V Patel, Amy B Foster, Kalpana K Patel, Maria S Stoll, Paul E Minkler, Hisashi Fujioka, Brian D Hoit, Martin E Young, Charles L Hoppel, Margaret P Chandler
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 79 Issue 2 Pg. 331-40 (Jul 15 2008) ISSN: 0008-6363 [Print] England
• PMID: 18339649 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Blood Glucose
• Dietary Fats
• Electron Transport Chain Complex Proteins
• Fatty Acids, Nonesterified
• Insulin
• Leptin
• Triglycerides
• acylcarnitine
• Acyl-CoA Dehydrogenase
• Carnitine

Topics

• Acyl-CoA Dehydrogenase (metabolism)
• Adiponectin (metabolism)
• Animals
• Blood Glucose (metabolism)
• Carnitine (analogs & derivatives, metabolism)
• Dietary Fats (pharmacology)
• Disease Models, Animal
• Electron Transport Chain Complex Proteins (metabolism)
• Fatty Acids, Nonesterified (metabolism)
• Heart Failure (enzymology, physiopathology)
• Insulin (metabolism)
• Leptin (metabolism)
• Male
• Mitochondria, Heart (metabolism)
• Myocardial Contraction (drug effects, physiology)
• Rats
• Rats, Wistar
• Triglycerides (metabolism)