Cardiac specific knock-down of peroxisome proliferator activated receptor α prevents fasting-induced cardiac lipid accumulation and reduces perilipin 2

Fig 1. Reduction in cardiac PPARα does not induce cardiac hypertrophy or reduce cardiac function. A. Hearts were weighed at baseline to assess cardiac hypertrophy. n = 12–19. B. Hearts from mice fasted for 16 hrs were weighed. n = 6–10. Heart weights were normalized to tibia length. C. Ejection Fraction and D. LV Diameter in Diastole were measured via echocardiography. n = 6. E. Exercise capacity was assessed via treadmill. n = 5–10. This was done in a single session in one day. F. Exercise capacity was assessed via treadmill in fasted mice. n = 5–6. This was done in a single session in one day. G. Genotyping of mouse tissues using genomic DNA. ~ 450 bp band indicates Mer-Cre-Mer (MCM) cut the loxp flanked sequence in the PPARα gene. H. PPARα protein levels were measured in hearts. n = 6–8. Representative blots are from the same membrane. I. PPARα mRNA levels were measured in hearts. n = 4–5 Values are mean ± SEM. * p<0.05 compared to Control.

Fig 2. Reduction in myocardial PPARα prevents cardiac triglyceride accumulation. Mice were fasted for 16 hrs and then A. serum fatty acid levels and B. triglyceride levels were measured in hearts. Values are mean ± SEM; n = 5–12; * p<0.05 compared to Control Fed, # p<0.05 compared to cPPAR-/- Fed.

Fig 3. FASN was not altered in fasting in mice with reduced myocardial PPARα. Mice were fasted for 16 hrs and then A. FASN mRNA and B. SCD1 was measured in the hearts. Values are mean ± SEM. n = 5–11; > p<0.05 compared to Control Fasted.

Fig 4. Reduction in myocardial PPARα mice lowers cardiac Plin2. Mice were fasted for 16 hrs and A. Plin2 and B. Plin5 protein levels were measured in heart. C Representative western blots [Cont (Control); KO (cPPAR-/-)]. D. Lipase activity in heart. Values are mean ± SEM; n = 5–12; * p<0.05 compared to Control Fed; > p<0.05 compared to Control Fasted.

Fig 5. Control or fasted mice with reduced myocardial PPARα do not have elevated levels of protein oxidation. Mice were fasted were 16 hrs and then A. 4-HNE and B. protein carbonylation levels were measured in heart. C. Representative western blot images. Values are mean ± SEM. n = 5–12.