Dietary lipids regulate β-oxidation enzyme gene expression in the developing rat kidney

Abstract

This study examines the ability of dietary lipids to regulate gene expression of mitochondrial and peroxisomal fatty acid β-oxidation enzymes in the kidney cortex and medulla of 3-wk-old rats and evaluates the role of glucagon or of the α-isoform of peroxisome proliferator-activated receptor (PPARα) in mediating β-oxidation enzyme gene regulation in the immature kidney. The long-chain (LCAD) and medium-chain acyl-CoA dehydrogenases (MCAD) and acyl-CoA oxidase (ACO) mRNA levels were found coordinately upregulated in renal cortex, but not in medulla, of pups weaned on a high-fat diet from day 16 to 21. Further results establish that switching pups from a low- to a high-fat diet for only 1 day was sufficient to induce large increases in cortical LCAD, MCAD, and ACO mRNA levels, and gavage experiments show that this upregulation of β-oxidation gene expression is initiated within 6 h following lipid ingestion. Treatment of pups with clofibrate, a PPARα agonist, demonstrated that PPARα can mediate regulation of cortical β-oxidation enzyme gene expression, whereas glucagon was found ineffective. Thus dietary lipids physiologically regulate gene expression of mitochondrial and peroxisomal β-oxidation enzymes in the renal cortex of suckling pups, and this might involve PPARα-mediated mechanisms.

Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-alpha agonists

“…3 are involved in lipid metabolism, and have previously been shown to be regulated by PPAR agonists. These genes include bifunctional enzyme (peroxisomal -oxidation) (Bardot et al 1993), Cyp4A10 (microsomal -hydroxylation) (Bell et al 1993), acetyl-CoA C-acetyltransferase (mitochondrial -oxidation) (Gould-Rothberg et al 2001), beta-ketothiolase (mitochondrial -oxidation), longchain-acyl-CoA dehydrogenase (mitochondrial -oxidation) (Ouali et al 1998), and long-chainfatty-acyl-CoA synthetase (fatty acid activation) (Schoonjans et al 1995). The regulation of HMG-CoA-synthase (ketone body synthesis) (Rodriguez et al 1994) has also been described previously.…”

Expression of Peroxisome Proliferator-Activated Receptor Isoform Proteins in the Rat Kidney

“…Regarding PPAR-α, it is known to be involved in the control of fatty acid β-oxidation (4,5). PPAR-α is also reported to regulate cytochrome P450 4A genes through their PPRE at proximal tubules in the kidney (4,25), and may regulate sodium metabolism (4) and blood pressure (26).…”

“…There are 3 known isoforms of PPARs, PPAR-α, Recently, several studies have suggested the functional significance of PPARs in renal pathophysiology (4). It is assumed that PPAR-α is involved in the control of fatty acid β-oxidation and the regulation of cytochrome P450 4A genes in the kidney (4,5), and this isoform may affect sodium retention (4). Moreover, Kamijo et al recently demonstrated that PPAR-α in the proximal tubules was involved in the maintenance of ATP homeostasis to degrade absorbed proteins (6).…”

Regulation of Fatty Acid Transport Protein and Mitochondrial and Peroxisomal β-Oxidation Gene Expression by Fatty Acids in Developing Rats

“…The mitochondrial enzyme cDNA probes used in this study were rat MCAD EcoRI fragment of 871 bp (13) and rat LCAD EcoRI fragment of 1200 bp (14). A 559-bp ACO cDNA (15) and a 717-bp cDNA comprising part of the D and E domains of the rat PPAR␣ (16) were obtained by reverse transcription coupled to PCR as described elsewhere (17). For FATP, the hybridization was performed with the 1.3-kb BamH1-BglII fragment of mouse cDNA (9).…”