Increased peroxisomal fatty acid beta-oxidation and enhanced expression of peroxisome proliferator-activated receptor-alpha in diabetic rat liver

Mol Cell Biochem. 1999 Apr;194(1-2):227-34. doi: 10.1023/a:1006930513476.

Abstract

To determine whether the increased fatty acid beta-oxidation in the peroxisomes of diabetic rat liver is mediated by a common peroxisome proliferation mechanism, we measured the activation of long-chain (LC) and very long chain (VLC) fatty acids catalyzed by palmitoyl CoA ligase (PAL) and lignoceryl CoA ligase and oxidation of LC (palmitic acid) and VLC (lignoceric acid) fatty acids by isotopic methods. Immunoblot analysis of acyl-CoA oxidase (ACO), and Northern blot analysis of peroxisome proliferator-activated receptor (PPAR-alpha), ACO, and PAL were also performed. The PAL activity increased in peroxisomes and mitochondria from the liver of diabetic rats by 2.6-fold and 2.1 -fold, respectively. The lignoceroyl-CoA ligase activity increased by 2.6-fold in diabetic peroxisomes. Palmitic acid oxidation increased in the diabetic peroxisomes and mitochondria by 2.5-fold and 2.7-fold, respectively, while lignoceric acid oxidation increased by 2.0-fold in the peroxisomes. Immunoreactive ACO protein increased by 2-fold in the diabetic group. The mRNA levels for PPAR-alpha, ACO and PAL increased 2.9-, 2.8- and 1.6-fold, respectively, in the diabetic group. These results suggest that the increased supply of fatty acids to liver in diabetic state stimulates the expression of PPAR-alpha and its target genes responsible for the metabolism of fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Acyl-CoA Oxidase
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Carbon Radioisotopes
  • Coenzyme A Ligases / genetics
  • Coenzyme A Ligases / metabolism
  • Diabetes Mellitus, Experimental / metabolism*
  • Fatty Acids / metabolism*
  • Liver / enzymology
  • Liver / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microbodies / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Repressor Proteins*
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Abcd3 protein, rat
  • Carbon Radioisotopes
  • Fatty Acids
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Oxidoreductases
  • Acyl-CoA Oxidase
  • Coenzyme A Ligases
  • FAA2 protein, S cerevisiae
  • long-chain-fatty-acid-CoA ligase