Objective To explore the effect of hypoxic exercise on Irisin secretion of obese rats with a palmitic acid-induced lipid accumulation in L6 myotubes and a high-fat diet-induced model.Methods L6 myotubes were treated with 750 μmol/L palmitic acid to induce lipid accumulation and subsequently divided into four groups of normoxia(N),exercise(E),hypoxia(H),and hypoxic exer-cise(HE).Hypoxic conditions(1%O2)were used to simulate a low-oxygen environment,while AICAR stimulation was applied to the E and HE groups to mimic exercise.Eighty 3-week-old Sprague-Dawley rats were fed a high-fat diet for 16 weeks to establish an obesity model.Fifty obese rats that met the criteria were then selected and randomly assigned according to their body weight into five groups of normoxia-sedentary(NC),normoxia-exercise(NE),hypoxia-sedentary(HC),high-liv-ing high-training(HH),and low-living high-training(LH),each of 10.The hypoxic environment was set at 13.6%O2(simulating 3,500 m altitude).Then the NE,HH and LH groups performed daily one-hour treadmill training(NE:20 m/min;HH and LH:16 m/min),5 days/week for 4 weeks.After the intervention,the body composition was measured using dual-energy X-ray absorptiometry(DEXA),while Irisin concentrations in cell culture media and rat serum were determined by using the enzyme-linked immunosorbent assay.Moreover,fibronectin type Ⅲ domain-containing 5(FNDC5)mRNA expression in L6 cells and rat skeletal muscle was measured by quantitative polymerase chain reaction(qPCR),while FNDC5 and silent information regulator 1-peroxisome proliferators-activated re-ceptor γ coactivator lalpha(SIRT1-PGC-1α)pathway proteins were analyzed using Western blotting.Results(1)Cell experiments:①Compared with the N group,there were significantly higher Irisin lev-els in the culture medium of the E,H,and HE groups(P<0.01,P<0.05),as well as elevated FNDC5 mRNA and protein expression in the E and HE groups(P<0.05,P<0.01).Moreover,the Iri-sin concentration and FNDC5 protein levels of group HE were significantly higher than group E(P<0.05).②Compared with group N,significantly increased SIRT1 and PGC-1α protein expression was observed in groups E and HE(P<0.05,P<0.01).(2)Animal experiments:①Compared with the NC group,body weight and fat mass were significantly lower in the NE,LH,and HH groups(P<0.01),with further reductions observed in the HH group compared with the NE group(P<0.05).② Com-pared with group NC,groups NE,LH,and HH exhibited higher serum Irisin levels and increased FNDC5 mRNA and protein expression in skeletal muscle(P<0.05,P<0.01).Furthermore,FNDC5 pro-tein expression of the HH group was significantly higher than the NE group(P<0.05).③ Compared with the NC group,SIRT1 and PGC-1α protein levels were significantly upregulated in the NE,LH,and HH groups(P<0.05,P<0.01).Conclusion Hypoxic exercise effectively alleviates obesity,reduces body weight and fat accumulation in high-fat diet-induced obese rats,and enhances FNDC5 expres-sion and Irisin secretion,which may be mediated through activation of the SIRT1-PGC-1α signaling pathway.Moreover,among the different hypoxic exercise modalities,the"high-living high-training"protocol appears to have greater benefits in promoting FNDC5/Irisin expression and facilitating weight and fat reduction in obese rats.

Objective To explore the effect of hypoxic exercise on Irisin secretion of obese rats with a palmitic acid-induced lipid accumulation in L6 myotubes and a high-fat diet-induced model.Methods L6 myotubes were treated with 750 μmol/L palmitic acid to induce lipid accumulation and subsequently divided into four groups of normoxia(N),exercise(E),hypoxia(H),and hypoxic exer-cise(HE).Hypoxic conditions(1%O2)were used to simulate a low-oxygen environment,while AICAR stimulation was applied to the E and HE groups to mimic exercise.Eighty 3-week-old Sprague-Dawley rats were fed a high-fat diet for 16 weeks to establish an obesity model.Fifty obese rats that met the criteria were then selected and randomly assigned according to their body weight into five groups of normoxia-sedentary(NC),normoxia-exercise(NE),hypoxia-sedentary(HC),high-liv-ing high-training(HH),and low-living high-training(LH),each of 10.The hypoxic environment was set at 13.6%O2(simulating 3,500 m altitude).Then the NE,HH and LH groups performed daily one-hour treadmill training(NE:20 m/min;HH and LH:16 m/min),5 days/week for 4 weeks.After the intervention,the body composition was measured using dual-energy X-ray absorptiometry(DEXA),while Irisin concentrations in cell culture media and rat serum were determined by using the enzyme-linked immunosorbent assay.Moreover,fibronectin type Ⅲ domain-containing 5(FNDC5)mRNA expression in L6 cells and rat skeletal muscle was measured by quantitative polymerase chain reaction(qPCR),while FNDC5 and silent information regulator 1-peroxisome proliferators-activated re-ceptor γ coactivator lalpha(SIRT1-PGC-1α)pathway proteins were analyzed using Western blotting.Results(1)Cell experiments:①Compared with the N group,there were significantly higher Irisin lev-els in the culture medium of the E,H,and HE groups(P<0.01,P<0.05),as well as elevated FNDC5 mRNA and protein expression in the E and HE groups(P<0.05,P<0.01).Moreover,the Iri-sin concentration and FNDC5 protein levels of group HE were significantly higher than group E(P<0.05).②Compared with group N,significantly increased SIRT1 and PGC-1α protein expression was observed in groups E and HE(P<0.05,P<0.01).(2)Animal experiments:①Compared with the NC group,body weight and fat mass were significantly lower in the NE,LH,and HH groups(P<0.01),with further reductions observed in the HH group compared with the NE group(P<0.05).② Com-pared with group NC,groups NE,LH,and HH exhibited higher serum Irisin levels and increased FNDC5 mRNA and protein expression in skeletal muscle(P<0.05,P<0.01).Furthermore,FNDC5 pro-tein expression of the HH group was significantly higher than the NE group(P<0.05).③ Compared with the NC group,SIRT1 and PGC-1α protein levels were significantly upregulated in the NE,LH,and HH groups(P<0.05,P<0.01).Conclusion Hypoxic exercise effectively alleviates obesity,reduces body weight and fat accumulation in high-fat diet-induced obese rats,and enhances FNDC5 expres-sion and Irisin secretion,which may be mediated through activation of the SIRT1-PGC-1α signaling pathway.Moreover,among the different hypoxic exercise modalities,the"high-living high-training"protocol appears to have greater benefits in promoting FNDC5/Irisin expression and facilitating weight and fat reduction in obese rats.