Hypoxia in vivo decreases peroxisome proliferator-activated receptor alpha-regulated gene expression in rat heart

We tested the hypothesis that hypoxia decreases PPAR alpha -regulated gene expression in heart muscle in vivo. In two rat models of systemic hypoxia ( cobalt chloride treatment and iso-volemic hemodilution), transcript levels of PPAR alpha and PPARa-regulated genes (pyruvate dehydrogenase kinase 4 (P DK4), muscle carnitine palmitoyltransferase-I (mCPT-I), and malonyl-CoA dec arboxylase (MCD)) were measured using real-time quantitative RT-PCR. Data w ere normalized to the housekeeping gene beta -actin. Atrial natriuretic fac tor (ANF) and pyruvate dehydrogenase kinase 2 (PDK2), which are not regulat ed by PPARa, served as controls. CoCl2 treatment decreased PPARa, PDK4, mCP T-I, and MCD mRNA levels. Iso-volemic anemia also caused a significant decr ease in PPARa, PDK4, and MCD mRNA levels. Transcript levels of mCPT-I showe d a slight, but not significant decrease (P = 0.08). Gene expression of bet a -actin, APM, and PDK2 did not change with either CoCl2 treatment nor with anemia. Myocardial PPARa-regulated gene expression is decreased in two mod els of hypoxia in vivo. These results suggest a transcriptional mechanism f or decreased fatty oxidation and increased reliance of the heart for glucos e during hypoxia. (C) 2001 Academic Press.