Effect of nutritional vitamin A deficiency on lipid metabolism in the rat heart: Its relation to PPAR gene expression

ObjectiveWe studied the effect of dietary vitamin A deprivation on lipid composition and mRNA expression of regulatory enzymes involved in rat heart energetic lipid metabolism and its relation to the expression of peroxisome proliferator-activated receptor (PPAR) and retinoid X receptor (RXR) genes.MethodsMale Wistar 21-d-old rats were fed for 3 mo with a vitamin A–free diet (vitamin A–deficient group) and the same diet plus 8 mg of retinol palmitate per kilogram of diet (control group). One group of deficient animals received the control diet 15 d before sacrifice (vitamin A–refed group). Heart ventricular and mitochondrial lipid contents were determined. Lipid synthesis was measured using radioactive precursors and acetyl-coenzyme A carboxylase and mitochondrial carnitine palmitoyltransferase-I (CPT-I) activities using radioactive substrates. Fatty acid composition of mitochondrial phospholipids was analyzed by gas–liquid chromatography. Heart expression of acetyl-coenzyme A carboxylase, CPT-I, PPAR-α, PPAR-β, RXR-α, and RXR-β was assessed by reverse transcriptase polymerase chain reaction, and CPT-I expression was also measured by real-time polymerase chain reaction.ResultsVitamin A deficiency induced changes in heart ventricular lipid content and synthesis. Mitochondrial cardiolipin decreased and the proportion of phospholipids/saturated fatty acids increased. Heart activity and mRNA levels of CPT-I and expression of PPAR-α and PPAR-β genes were enhanced, whereas acetyl-coenzyme A carboxylase activity diminished. Furthermore, vitamin A deficiency decreased heart mRNA levels of RXRs. Vitamin A refeeding reverted most of the observed changes.ConclusionLipid metabolism is significantly modified in hearts of vitamin A–deficient rats. Alteration of mitochondrial energetic processes by modifying the activity and gene expressions of the regulatory enzymes is associated with a high PPAR expression induced by vitamin A deprivation.