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DOI: 10.1055/s-0035-1544330
High Fat Diet Preserves Cardiac Function but Impairs Survival and Mitochondrial Function under Pressure Overload
Background: High fat diet (HFD) induces insulin resistance and obesity, conditions associated with worse outcome in heart failure. However, high fat diet may also be protective in cardiac disease. We assessed the impact of HFD under pressure overload on contractile function, survival and mitochondrial function.
Methods: Pregnant rats were fed HFD or standard diet (SD). Diets were maintained during lactation and in offsprings. At three weeks of age, pups underwent transverse aortic constriction (TAC) to induce pressure overload.
Results: HFD increased basal glucose levels (mmol/l: SD 4,0 versus HFD 5,4 mmol/L; p < 0,05) and impaired glucose tolerance (AUC: SD 807 ± 31 versus HFD 1063 ± 31; p < 0,05). HFD-TAC caused more cardiac hypertrophy than SD-TAC (LVWD SD 3,45 ± 0,16 versus SD-TAC 5,22 ± 0,32 versus HFD-TAC 6,36 ± 0,29 mm). In SD-TAC, hearts showed diastolic dysfunction after 10 weeks and were dilated with systolic dysfunction at 20 weeks (LVEDD: 7,64 ± 0,18 versus 8,58 ± 0,09 versus 9,12 ± 0,18). In HFD-TAC, diastolic dysfunction was alleviated (E/E': 16,6 ± 1,1 versus 33,9 ± 2,6 versus 25,0 ± 2,1) and systolic function was preserved (FS: 48,2 ± 1,2 versus 23,6 ± 0,8 versus 44,5 ± 1,4). In contrast, survival and mitochondrial function at 20 weeks of TAC was significantly reduced with HFD (mean survival time SD-TAC 19,1 versus HFD-TAC 12,2 weeks, p < 0,05). Maximal respiratory capacity of isolated mitochondria was dramatically reduced (natomsO/min/mg pyruvate/malate: 796 ± 95 versus 204 ± 15 versus 195 ± 10, p < 0.05). This reduction was even greater with succinate as substrate in HFD-TAC (739 ± 99 versus 580 ± 56 versus 361 ± 36, p < 0.05).
Conclusion: High fat diet preserves cardiac contractile function but impairs survival and mitochondrial function under pressure overload.