Metabolic adaptation follows contractile dysfunction in the heart of obese Zucker rats fed a high-fat "Western" diet.
The normal heart responds to changes in its metabolic milieu by changing relative oxidation rates of energy-providing substrates. We hypothesized that this flexibility is lost when genetically obese rats are fed a high-caloric, high-fat "Western" diet (WD). Male Zucker obese (ZO) and Zucker lean (ZL) rats were fed either control or WD composed of 10 kcal% and 45 kcal% fat, respectively, for 7 or 28 days. Cardiac triglycerides and mRNA transcript levels were measured in situ. Substrate oxidation rates and cardiac power were measured ex vivo. Hearts from ZO rats fed WD for 7 days showed decreased cardiac power and increased cardiac triglyceride content, but no change in oleate oxidation rates or mRNA transcript levels of pyruvate dehydrogenase kinase-4 (PDK-4), uncoupling protein-3 (UCP-3), and mitochondrial (MTE-1) and cytosolic thioesterase-1(CTE-1). When fed WD for 28 days, ZO rats showed no further decrease in cardiac power and no further increase in intramyocardial triglyceride levels compared to ZO rats fed the same diet for 7 days only, but did show significantly increased oleate oxidation rates and transcript levels of CTE-1, MTE-1, PDK-4, and UCP-3. In contrast, hearts from ZL rats fed WD showed increased rates of oleate oxidation and increased transcript levels of the fatty acid responsive genes investigated, and no further deterioration of contractile function. We conclude that exposing a genetic model of obesity to the nutrient stress of WD results in an early reversible loss of metabolic flexibility of the heart that is accompanied by contractile dysfunction.
Burgmaier
Mathias
M
Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School, Houston, Texas, USA.
Sen
Shiraj
S
Philip
Femi
F
Wilson
Christopher R
CR
Miller
Charles C
CC
Young
Martin E
ME
Taegtmeyer
Heinrich
H
D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D002149:Energy Intake; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology*; D019301:Oleic Acid / Q000378:metabolism*; D010084:Oxidation-Reduction; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D000071247:Uncoupling Protein 3
D004041:Dietary Fats; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger; D014280:Triglycerides; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D019301:Oleic Acid; D017346:Protein Serine-Threonine Kinases; D013869:Thiolester Hydrolases; C546434:Acot2 protein, rat; D010170:Palmitoyl-CoA Hydrolase