Western diet changes cardiac acyl-CoA composition in obese rats: a potential role for hepatic lipogenesis.
The "lipotoxic footprint" of cardiac maladaptation in diet-induced obesity is poorly defined. We investigated how manipulation of dietary lipid and carbohydrate influenced potential lipotoxic species in the failing heart. In Wistar rats, contractile dysfunction develops at 48 weeks on a high-fat/high-carbohydrate "Western" diet, but not on low-fat/high-carbohydrate or high-fat diets. Cardiac content of the lipotoxic candidates--diacylglycerol, ceramide, lipid peroxide, and long-chain acyl-CoA species--was measured at different time points by high-performance liquid chromatography and biochemical assays, as was lipogenic capacity in the heart and liver by qRT-PCR and radiometric assays. Changes in membranes fluidity were also monitored using fluorescence polarization. We report that Western feeding induced a 40% decrease in myocardial palmitoleoyl-CoA content and a similar decrease in the unsaturated-to-saturated fatty acid ratio. These changes were associated with impaired cardiac mitochondrial membrane fluidity. At the same time, hepatic lipogenic capacity was increased in animals fed Western diet (+270% fatty acid elongase activity compared with high-fat diet), while fatty acid desaturase activity decreased over time. Our findings suggest that dysregulation of lipogenesis is a significant component of heart failure in diet-induced obesity.
Harmancey
Romain
R
Department of Internal Medicine, Division of Cardiology, University of Texas Medical School at Houston, TX 77030, USA.
Wilson
Christopher R
CR
Wright
Nathan R
NR
Taegtmeyer
Heinrich
H
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004041:Dietary Fats / Q000009:adverse effects; D005227:Fatty Acids / Q000096:biosynthesis / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism
D000214:Acyl Coenzyme A; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005227:Fatty Acids; D013230:Stearoyl-CoA Desaturase