The Effect Of AMPK-ACC-CPT Pathway To Free Fatty Acid Metabolism Of Sepisis Rats

Experimental background:AMP-activated protein kinase(AMPK) is a phylogenetically conserved serine/thereonine protein kinase which has been proposed to act as a'metabolic master switch'mediating the celluar adapataion to enviromental or nutritional stress factors. In our study, we test the level of AMPK signaling pathway activation and free fatty acid metabolism in endotoxin rat。Experiment purpose:The purpose of this study was to investigate the relation of free fatty acid metabolism and its possible mechanism AMPK pathway in endotoxic rats.Experimental Methods:Endotoxemia was induced by a slow intravenous injection of 5mg/kg lippolysaccharide via tail vein of rats。24 wistar rats were randomly divided into two groups as follows:control group (n=12), endotoxemia group(n=12), every group further divided into 6 hours,24 hours subgroup,6 rats for each subgroup. At the two time points, rats in all groups were sacrificed tissue sample from liver,heart.SOL. long extensor muscle digits to measure free fatty acid content, AMPK phosphorylation level, ACC phosphorylation level and CPT protein level.Results:1)6 hours group of heart, liver free fatty acid content increased compared with control group after injecting of LPS, (Heart102.2459±5.95506 vs120.1584±9.40634,Liver 77.8618±14.59484 vs104.0993±5.34602),6 hours group soleus muscle, extensor digitorum longus free fatty acid showed no significant change. 24 hours group of heart, liver free fatty acid content decreased compared with control group after injecting of LPS (Heart102.8942.98192vs89.1406±4.70044, Liver 77.8618±14.59484vs 75.6402±3.14461),24 hours group soleus muscle, extensor digitorum longus free fatty acid also showed no significant change。2) 6 hours group of heart, liver, soleus muscle, extensor digitorum longus AMPK phosphorylation levels compared with normal control group no significant change, 24-hour group of heart, liver, AMPK phosphorylation levels increased compared with control group (Heart 0.6814±0.21652vs0.3380±0.11422,Liver0.6188±0.04802vs0.5452±0.06245)。3) 6 hours group of heart, liver, soleus muscle, extensor digitorum longus ACC phosphorylation level showed no significant change compared with normal control group,24-hour group of heart, liver, ACC phosphorylation levels increased compared with control group (Heart 0.4141±.03505vs0.7036±0.07736,Liver0.6257±0.03421vs 0.8758±0.05813).4) 6 hours group of heart, liver, soleus muscle, extensor digitorum longus CPT protein levels showed no significant change compared with normal control group, 24-hour group of heart, liver CPT protein levels increased compared with control group (Heart 1.1005±0.11626vs1.9111±0.19417,Liver1.3007±0.20310vs2.0715±0.22773)。Conclusion:LPS can produce dynamic changes in free fatty acid metobolism of heart and liver. After 6 hour of LPS administration, fatty acid content of heart and liver increased, accompany AMPK-ACC-CPT signaling pathway of heart and liver having no alter。After 24 hour of LPS injection, AMPK-ACC-CPT signaling pathway of heart and liver activated, free fatty acid oxidation increased, then free fatty acid content of heart and liver decreased。After LPS administration, AMPK-ACC-CPT signaling pathway do not participate free fatty acid metabolism of Soleus muscle and extensor digitorum longus.