Effects of a high saturated fat diet on cardiac hypertrophy and dysfunction in response to pressure overload

Background: Dietary lipid content effects activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and may accelerate cardiac hypertrophy and dysfunction in response to pressure overload. This study investigated the effects of a high-fat diet on the development of cardiac hypertrophy. Methods and Results: C57BL/6J mice (n = 14-16/group) underwent transverse aortic constriction (TAC) or sham surgery and were fed either standard low-fat diet (STD; 10% fat) or a high-fat diet (HFD; 60% fat) for 16 weeks. Sham mice showed no differences between STD, and HFD for heart mass or echocardiographic parameters despite greater plasma free fatty acid and leptin concentrations with HFD. TAC increased heart mass and decreased ejection fraction similarly in both groups. Left ventricular end systolic and diastolic diameters with TAC were increased compared with shams on the HFD (P < .05), but were not different from STD TAC mice. High-fat feeding increased expression of PPAR-alpha-regulated genes. The activity of medium chain acyl-coenzyme A dehydrogenase (MCAD), a marker of fatty acid oxidation capacity, was increased in HFD TAC mice compared with STD, consistent with PPAR-alpha activation. Conclusions: Increased fat intake prevented the fall in MCAD activity and did not exacerbate the hypertrophic response to TAC compared with a low-fat diet.