In this work, we show that 5-aminoimidazole-4-carboxamide riboside (AICAR), a well-known AMPK activator [22], controls the expression of PPAR-target genes in HL-1 cardiomyocytes, counters the intramyocellular lipid accumulation induced by high palmitate/high insulin (HP/HI), and prevents the development of insulin resistance in these cells. The gene discussed is PPARA; the disease is Insulin resistance.