Objective To explore the effect of aerobic exercise on adipogenesis and insulin resis-tance(IR)in mice on high-fat diet,and to explore the mechanism of aerobic exercise regulating obe-sity-related long noncoding RNA(lnc-ORA)in this process.Methods Thirty-six 8-week-old male C57BL/6J mice,weighing 21.4±0.92 g,were randomized into a normal control group(NC),a high-fat control group(HC)and the high-fat exercise group(HE),each of 12,after one-week acclimatiz-ing feeding.Group NC was fed on normal diet,while the high-fat groups were given high-fat food for 4 weeks.Then,group HE underwent daily 45-minute aerobic exercise on a 6%-incline treadmill at a speed of 18 m/min,6 days per week,for 8-week.After the intervention,the body weight,body length,and epididymal fat weight of all groups were measured,and the adipocyte size was observed.Moreover,lipid levels,glucose tolerance,insulin sensitivity,and expression of genes related to adipo-genesis(FASN,FABP4,and PPARγ)were examined,together with the expression levels of the rele-vant signaling axes(IRS-1/PI3K/AKT/mTOR/GLUT4)and related metrics(lnc-ORA,TNFα),and en-richment levels of peroxisome proliferator-activated receptor γ(PPARγ)promoter region for histone H3 acetylation(H3ac)and histone H3K4 trimethylation(H3K4me3).Results The body weight,epidid-ymal adipose tissue weight,and body mass index(Lee's index)of group HC were significantly higher(P<0.05)than group NC,and the above indexes of group HE were significantly lower(P<0.05)than group HC after 8 weeks of aerobic exercise intervention.The levels of total cholesterol(TC),low-den-sity lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)of the HC group were significantly higher than the NC group(P<0.05),and the lipid levels of the HE group im-proved significantly compared to the HC group(P<0.05).Moreover,the expression of adipogenesis-re-lated genes PPARγ,fatty acid synthase(FASN)and fatty acid binding protein 4(FABP4)up-regulat-ed significantly in group HC compared with group NC(P<0.05),while that of adipogenesis-related genes in group HE was significantly lower than group HC(P<0.05),with the adipocytes'size of HC group larger than the other two groups.What's more,the expression level of insulin receptor substrate 1(IRS-1)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamy-cin(mTOR)/glucose transporter type 4(GLUT4)pathway decreased significantly in group HC com-pared with group NC and HE(P<0.05;P<0.01,P<0.05).Meanwhile,both glucose tolerance and insu-lin sensitivity of group HC decreased significantly compared with the NC and HE groups(P<0.01,P<0.05;P<0.01,P<0.05).However,the expression of lnc-ORA and TNF-α increased significantly in group HC compared with group NC(P<0.01,P<0.05),but significantly down-regulated in group HE compared with group HC(P<0.05).The enriched levels of H3ac and H3K4me3 in the PPARγ promot-er region of group HC increased significantly compared with group NC(P<0.05),but decreased signifi-cantly in group HE compared with group HC(P<0.05).Conclusions Aerobic exercise reduces adipogen-esis via lnc-ORA/PPARγ and improves IR by modulating the IRS-1/PI3K/AKT/GLUT4 axis.

Objective To explore the effect of aerobic exercise on adipogenesis and insulin resis-tance(IR)in mice on high-fat diet,and to explore the mechanism of aerobic exercise regulating obe-sity-related long noncoding RNA(lnc-ORA)in this process.Methods Thirty-six 8-week-old male C57BL/6J mice,weighing 21.4±0.92 g,were randomized into a normal control group(NC),a high-fat control group(HC)and the high-fat exercise group(HE),each of 12,after one-week acclimatiz-ing feeding.Group NC was fed on normal diet,while the high-fat groups were given high-fat food for 4 weeks.Then,group HE underwent daily 45-minute aerobic exercise on a 6%-incline treadmill at a speed of 18 m/min,6 days per week,for 8-week.After the intervention,the body weight,body length,and epididymal fat weight of all groups were measured,and the adipocyte size was observed.Moreover,lipid levels,glucose tolerance,insulin sensitivity,and expression of genes related to adipo-genesis(FASN,FABP4,and PPARγ)were examined,together with the expression levels of the rele-vant signaling axes(IRS-1/PI3K/AKT/mTOR/GLUT4)and related metrics(lnc-ORA,TNFα),and en-richment levels of peroxisome proliferator-activated receptor γ(PPARγ)promoter region for histone H3 acetylation(H3ac)and histone H3K4 trimethylation(H3K4me3).Results The body weight,epidid-ymal adipose tissue weight,and body mass index(Lee's index)of group HC were significantly higher(P<0.05)than group NC,and the above indexes of group HE were significantly lower(P<0.05)than group HC after 8 weeks of aerobic exercise intervention.The levels of total cholesterol(TC),low-den-sity lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)of the HC group were significantly higher than the NC group(P<0.05),and the lipid levels of the HE group im-proved significantly compared to the HC group(P<0.05).Moreover,the expression of adipogenesis-re-lated genes PPARγ,fatty acid synthase(FASN)and fatty acid binding protein 4(FABP4)up-regulat-ed significantly in group HC compared with group NC(P<0.05),while that of adipogenesis-related genes in group HE was significantly lower than group HC(P<0.05),with the adipocytes'size of HC group larger than the other two groups.What's more,the expression level of insulin receptor substrate 1(IRS-1)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamy-cin(mTOR)/glucose transporter type 4(GLUT4)pathway decreased significantly in group HC com-pared with group NC and HE(P<0.05;P<0.01,P<0.05).Meanwhile,both glucose tolerance and insu-lin sensitivity of group HC decreased significantly compared with the NC and HE groups(P<0.01,P<0.05;P<0.01,P<0.05).However,the expression of lnc-ORA and TNF-α increased significantly in group HC compared with group NC(P<0.01,P<0.05),but significantly down-regulated in group HE compared with group HC(P<0.05).The enriched levels of H3ac and H3K4me3 in the PPARγ promot-er region of group HC increased significantly compared with group NC(P<0.05),but decreased signifi-cantly in group HE compared with group HC(P<0.05).Conclusions Aerobic exercise reduces adipogen-esis via lnc-ORA/PPARγ and improves IR by modulating the IRS-1/PI3K/AKT/GLUT4 axis.