Abstract: Objective:To observe the effects of long-term endurance exercise training on hypoxia-inducible factor 1α-peroxisome proliferator-activated receptor γ(HIF1α-PPARγ) signal pathway as well as downstream target genes expression in rats of chronic heart failure(HF) and explore the possible mechanism of exercise-induced improvement of lipid metabolic derangement.Methods:Thirty male SD rats were randomly divided into HF-control group(HF group) and HF-exercise group(HF+E group) after establishing pressure-overload HF model by transverse abdominal aortic constriction.Another 20 rats randomly divided into sham operation group(Sham group) and sham operation-exercise group(Sham+E group) were separated abdominal aorta but not ligated.The experiment initiated after 4-week rest:Sham+E group and HF+E group conducted 10-week treadmill exercise training and Sham group and HF group maintained resting state.After the experiment,maximal aerobic velocity(MAV) and exhaustive time(ET) were tested by incremental treadmill test;cardiac function including heart rate(HR),left ventricular end-diastolic diameter(LVEDD),left ventricular wall thickness(LVWT),fractional shortening(FS) and left ventricular ejection fraction(LVEF) were detected by ultrechocardiograph;body weight(BW),left ventricular weight(LVW),right ventricular weight(RVW) and left ventricular mass index(LVMI) were measured;myocardial triglyceride(TG) and fatty acid(FA) were evaluated by colorimetric method;FA β-oxidation rate(FOR) was determined by isotope method;myocardial HIF1α,PPARγ,glycerol-3-phosphate dehydrogenase(GPDH) and glycerol phosphate acyltransferase(GPAT) gene expression were measured by real-time Q-PCR and Western blotting.Results:Compared with Sham group,HF group MAV,ET,BW,LVEDD,FS and LVEF reduced(all P<0.01),LVW,LVMI,HR and LVWT elevated(all P<0.01);content of FA,TG increased and FOR decreased(all P<0.01);HIF1α mRNA lowered but protein level heightened,PPARγ,GPDH,GPAT mRNA and protein raised(all P<0.01).Compared with HF group,HF+E group MAV,ET,LVW,LVMI,LVEDD,FS and LVEF increased(all P<0.01),HR decreased(P<0.05);content of FA,TG reduced and FOR raised(all P<0.01);HIF1α mRNA elevated but protein level declined,PPARγ,GPDH,GPAT mRNA and protein lowered(all P<0.01).Conclusion:1) HIF1α protein overexpressed and HIF1α-PPARγ signal pathway activated continously in heart failure,activating downstream target genes which regulate lipid anabolism and leading to myocyte TG accumulation,FA oxidation and utilization reduction and decline of both cardiac function and exercise tolerance.2) Long-term endurance exercise training downregulated HIF1α expression and suppressed HIF1α signal pathway,thus reducing myocardial lipid accumlation,improving cardiac function and enhancing exercise tolerance.