Lard Intake Reduced Tetralinoleoyl Cardiolipin and Attenuated the Cardioprotective Effects of Exercise in Mice With Pressure Overload-Induced Heart Failure

Background: Exercise-based cardiac rehabilitation is effective for improving the prognosis of patients with heart failure (HF), but little is known about its interactions with dietary components. We investigated the impacts of dietary fat intake and its source on the cardioprotective effects of exercise in mice with HF. Methods and Results: Endurance exercise and diets with different fat composition, including a normal diet (NE: 11% fat), a soybean oil-rich diet (SE: 32% fat) and a lard-rich diet (LE: 32% fat), were provided for 4 weeks to mice with HF induced by transverse aortic constriction. Exercise improved left ventricular systolic function and suppressed cardiac hypertrophy in the NE and SE groups, but these effects were attenuated in the LE group. The LE group exhibited a reduction in linoleic acid content within mitochondrial phospholipids such as phosphatidylcholine and phosphatidylethanolamine, concurrent with the promotion of cardiolipin remodeling pathways. This resulted in a marked reduction in tetralinoleoyl cardiolipin (L 4 CL), which is crucial for maintaining mitochondrial membrane function. This was supported by the finding that assembly of mitochondrial respiratory chain supercomplexes was partially impaired in the LE group. Conclusions: Lard intake may attenuate the exercise-induced cardioprotective effects against HF by reducing myocardial L 4 CL levels and impairing mitochondrial supercomplex assembly involved in mitochondrial respiratory capacity.