Effects of fatty acids on mitochondrial β-oxidation enzyme gene expression in renal cell lines

Regulatory effects of fatty acids on gene expression of medium-chain acyl-CoA dehydrogenase (MCAD), a mitochondrial β-oxidation enzyme, were investigated in rabbit kidney cell lines derived from proximal tubule (RC.SV1), thick ascending limb of Henle's loop (RC.SV2), or collecting duct (RC.SV3). Exposure to long-chain fatty acids led to significant increases (2-fold) in MCAD mRNA abundance in RC.SV1 and RC.SV2 cells; kinetics and dose-response studies established that maximal MCAD gene stimulation was reached 4 h after addition of 50 μM oleate (C18:1) in the culture medium. These effects of fatty acids were totally abolished in the presence of 1 μg/ml actinomycin D, a transcription inhibitor. Staining of cellular lipids revealed that fatty acid-induced gene stimulation could occur in the absence of cellular fatty acid accumulation. Altogether, these data indicate that small changes in cellular fatty acid flux can have direct short-term effects on fatty acid oxidation enzyme gene expression in renal cells,...