Carnitine transporter OCTN2 and carnitine uptake in bovine kidney cells is regulated by peroxisome proliferator-activated receptor beta/delta

Abstract

BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARalpha), a central regulator of fatty acid catabolism, has recently been shown to be a transcriptional regulator of the gene encoding the carnitine transporter novel organic cation transporter 2 (OCTN2) in cattle. Whether PPARbeta/delta, another PPAR subtype, which has partially overlapping functions as PPARalpha and is known to share a large set of common target genes with PPARalpha, also regulates OCTN2 and carnitine transport in cattle is currently unknown. To close this gap of knowledge, we studied the effect of the PPARbeta/delta activator GW0742 on mRNA and protein levels of OCTN2 and carnitine uptake in the presence and absence of the PPARbeta/delta antagonist GSK3787 in the bovine Madin-Darby bovine kidney (MDBK) cell line. FINDINGS: Treatment of MDBK cells with GW0742 caused a strong increase in the mRNA level of the known bovine PPARbeta/delta target gene CPT1A in MDBK cells indicating activation of PPARbeta/delta. The mRNA and protein level of OCTN2 was clearly elevated in MDBK cells treated with GW0742, but the stimulatory effect of GW0742 on mRNA and protein level of OCTN2 was completely blocked by GSK3787. In addition, GW0742 increased Na+-dependent carnitine uptake, which is mediated by OCTN2, into MDBK cells, whereas treatment of cells with the PPARbeta/delta antagonist completely abolished the stimulatory effect of GW0742 on carnitine uptake. CONCLUSIONS: The present study shows for the first time that gene expression of the carnitine transporter OCTN2 and carnitine transport are regulated by PPARbeta/delta in bovine cells. These novel findings extend the knowledge about the molecular regulation of the OCTN2 gene and carnitine transport in cattle and indicate that regulation of OCTN2 gene expression and carnitine transport is not restricted to the PPARalpha subtype.