Aerobic Exercise Promotes The Expression Of ATGL And Reduces Inflammatory Factorts To Timprove Hepatic Steatosis Via Lnc SRA

Purpose: SRA is known to be a key long non-coding RNA that regulates lipolysis and inflammatory response.This study was designed to determine whether aerobic exercise inhibits SRA to promote ATGL expression as well as inhibits P38/JNK signaling to attenuate inflammation and improve hepatic steatosis.To further explore the potential mechanisms by which aerobic exercise regulates hepatic lipid metabolism via SRA.Methods: Thirty 8 week-old male C57BL/6J mice were divided into three groups after acclimatization: normal control group(NC,n=10),high-fat diet group(HFD,n=10),and high-fat diet with aerobic exercise group(HAE,n=10).The NC group under a normal diet,the HFD and HAE groups underwent a high-fat diet,and the HAE group exercised for45 min at 6% incline at 18 m/min speed 6% incline on the basis of the high-fat diet;six times a week for 8 weeks.Body weight was recorded weekly,and after the last exercise mice were dissected by overnight fasting anesthetic injection,blood was taken,and liver tissue was collected.Plasma was separated and the four lipids(TG,TC,LDL-C,HDL-C)and liver TG levels were measured by spectrophotometer;HE staining was performed to observe the pathological changes of liver steatosis.q PCR was performed to detect SRA,ATGL,pro-inflammatory factors(1L-6,TNF-?)and anti-inflammatory factor(1L-10)mRNA expression levels;WB was performed to detect liver Fox O1,ATGL and P38/JNK protein expression.Results: 1.Compared with the NC group,HFD group showed an increasing trend in body weight(P<0.05),serum TC,TG,LDL-C and HDL-C lipids were increased and liver TG content was significantly increased(P<0.05);HAE group showed a significant decrease in body weight compared with the HFD group.Compared with the HFD group,mice in the HAE group had significantly lower body weight,normal plasma TC and LDL-C levels,and significantly lower liver TG content(P<0.05).2.The total volume of the liver of the HFD group was swollen and had a yellowish-brown colour with a greasy feeling on the cut surface,and HE staining showed a significant increase in the size and number of droplets,punctate necrosis of hepatocytes and infiltration of inflammatory cells;the HAE group returned to a state similar to that of the NC group,with relatively orderly cell arrangement.3.Compared with the NC group,the expression of SRA in the liver of the HFD group was significantly induced(P<0.05),and was significantly inhibited in the HAE group under the aerobic exercise intervention(P<0.05).4.Compared with NC group,ATGL in liver tissues of mice in HFD were significantly lower(P<0.05),whereas the expression of ATGL in the HAE group was higher;the phosphorylation of Fox O1 in HFD group was down-regulated,it was up-regulated in the HAE group.5.Compared with HFD group,the levels of JNK/P38 signaling pathway proteins and its phosphorylation were inhibited,IL-6 and TNF-?mRNA were down-regulated,and factor IL-10 mRNA was increased in the HAE group.Conclusion: 1.Aerobic exercise promotes ATGL expression and inhibits inflammation to improve liver steatosis in mice on high-fat diet.2.The upregulation of ATGL expression after aerobic exercise intervention is related to the enhanced transcriptional activity of SRA-regulated Fox O1.3.The inhibition of inflammation is related to aerobic exercise through SRA-regulated P38/JNK signaling.