Ethanol impairs differentiation of human adipocyte stromal cells in culture

Alcohol Clin Exp Res. 2011 Sep;35(9):1584-92. doi: 10.1111/j.1530-0277.2011.01504.x. Epub 2011 May 20.

Abstract

Background: Bioinformatic resources suggest that adipose tissue expresses mRNAs for alcohol dehydrogenases (ADHs) and ALDH2, and epidemiological studies indicate that heavy alcohol use reduces adipose tissue mass. We therefore characterized the expression of alcohol metabolizing enzymes in human, rat and mouse adipose tissue, preadipocytes, and adipocytes, the ability of adipocytes to metabolize ethanol, and the effects of ethanol on differentiation of human adipose stromal cells (hASCs).

Methods: Adipose tissue, preadipocytes, and adipocytes were collected from rodents or from humans undergoing bariatric surgery. hASCs were differentiated in vitro using standard methods. Gene expression and cellular differentiation were analyzed by Western blotting, RT-PCR, and microscopy.

Results: Class I ADH was expressed in human > mouse > rat adipose tissue, whereas ALDH2 was high in all samples. ADH, catalase, and ALDH2 were induced during differentiation of hASCs. The presence of 50 mM ethanol markedly reduced the differentiation of hASCs; this effect was associated with inhibition of expression of transcription factors required for differentiation, but did not depend on the ability of the cells to metabolize ethanol.

Conclusions: Human adipose tissue expresses alcohol oxidizing enzymes. The presence of ethanol at physiologically relevant concentrations inhibits differentiation of hASCs. Ethanol could alter adipose tissue biology, inducing a form of acquired lipodystrophy, which is consistent with epidemiological studies.

Publication types

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

MeSH terms

  • Acetyl-CoA Carboxylase / biosynthesis
  • Actins / metabolism
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / enzymology
  • Adipocytes / metabolism*
  • Adipose Tissue / cytology
  • Adipose Tissue / enzymology
  • Adipose Tissue / metabolism*
  • Alcohol Dehydrogenase / biosynthesis*
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Central Nervous System Depressants / metabolism
  • Central Nervous System Depressants / toxicity
  • Cytochrome P-450 CYP2E1 / biosynthesis
  • Ethanol / metabolism*
  • Ethanol / toxicity*
  • Female
  • Gene Expression
  • Humans
  • Male
  • Mice
  • PPAR gamma / biosynthesis
  • Rats
  • Retinoid X Receptors / biosynthesis
  • Sterol Regulatory Element Binding Protein 1 / biosynthesis
  • Stromal Cells / cytology
  • Stromal Cells / drug effects*
  • Stromal Cells / enzymology
  • Stromal Cells / metabolism*
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured

Substances

  • Actins
  • Central Nervous System Depressants
  • PPAR gamma
  • Retinoid X Receptors
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors
  • Ethanol
  • Alcohol Dehydrogenase
  • Cytochrome P-450 CYP2E1
  • Acetyl-CoA Carboxylase