AICAR Protects against High Palmitate/High Insulin-Induced Intramyocellular Lipid Accumulation and Insulin Resistance in HL-1 Cardiac Cells by Inducing PPAR-Target Gene Expression

Here we studied the impact of 5-aminoimidazole-4-carboxamide riboside (aicar),a well-known ampk activator,on cardiac metabolic adaptation. ampk activation by aicar was confirmed by increased phospho-thr172-ampk and phospho-ser79-acc protein levels in hl-1 cardiomyocytes. then,cells were exposed to aicar stimulation for 24 h in the presence or absence of the ampk inhibitor compound c,and the mrna levels of the three ppars were analyzed by real-time rt-pcr. treatment with aicar induced gene expression of all three ppars,but only the ppara and pparg regulation were dependent on ampk. next,we exposed hl-1 cells to high palmitate/high insulin (hp/hi) conditions either in presence or in absence of aicar,and we evaluated the expression of selected ppar-targets genes. hp/hi induced insulin resistance and lipid storage was accompanied by increased cd36,acot1,and ucp3 mrna levels. aicar treatment induced the expression of acadvl and glut4,which correlated to prevention of the hp/hi-induced intramyocellular lipid build-up,and attenuation of the hp/hi-induced impairment of glucose uptake. these data support the hypothesis that aicar contributes to cardiac metabolic adaptation via regulation of transcriptional mechanisms. © 2015 ricardo rodríguez-calvo et al.