Dehydroepiandrosterone down-regulates the expression of peroxisome proliferator-activated receptor gamma in adipocytes

Endocrinology. 2003 Jan;144(1):253-9. doi: 10.1210/en.2002-220039.

Abstract

Dehydroepiandrosterone (DHEA) is expected to have a weight-reducing effect. In this study, we evaluated the effect of DHEA on genetically obese Otsuka Long Evans Fatty rats (OLETF) compared with Long-Evans Tokushima rats (LETO) as control. Feeding with 0.4% DHEA-containing food for 2 wk reduced the weight of sc, epididymal, and perirenal adipose tissue in association with decreased plasma leptin levels in OLETF. Adipose tissue from OLETF showed increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma) protein, which was prevented by DHEA treatment. Further, we examined the effect of DHEA on PPARgamma in primary cultured adipocytes and monolayer adipocytes differentiated from rat preadipocytes. PPARgamma protein level was decreased in a time- and concentration-dependent manner, and DHEA significantly reduced mRNA levels of PPARgamma, adipocyte lipid-binding protein, and sterol regulatory element-binding protein, but not CCAAT/enhancer binding protein alpha. DHEA-sulfate also reduced the PPARgamma protein, but dexamethasone, testosterone, or androstenedione did not alter its expression. In addition, treatment with DHEA for 5 d reduced the triglyceride content in monolayer adipocytes. These results suggest that DHEA down-regulates adiposity through the reduction of PPARgamma in adipocytes.

MeSH terms

  • Adipocytes / chemistry
  • Adipocytes / metabolism*
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Carrier Proteins / genetics
  • Cell Differentiation
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • Dehydroepiandrosterone / administration & dosage
  • Dehydroepiandrosterone / pharmacology*
  • Dehydroepiandrosterone Sulfate / pharmacology
  • Diet
  • Dose-Response Relationship, Drug
  • Epididymis
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Gene Expression Regulation / drug effects*
  • Kinetics
  • Leptin / blood
  • Male
  • Neoplasm Proteins*
  • Nerve Tissue Proteins*
  • Obesity / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred OLETF
  • Rats, Long-Evans
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors / analysis
  • Transcription Factors / genetics*
  • Triglycerides / analysis

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • CCAAT-Enhancer-Binding Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Fabp7 protein, rat
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Leptin
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Srebf1 protein, rat
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors
  • Triglycerides
  • Dehydroepiandrosterone
  • Dehydroepiandrosterone Sulfate