Chronic ethanol feeding suppresses beta-adrenergic receptor-stimulated lipolysis in adipocytes isolated from epididymal fat

Li Kang, Laura E. Nagy (Lead / Corresponding author)

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Chronic ethanol consumption disrupts G protein-dependent signaling pathways in rat adipocytes. Because lipolysis in adipocytes is regulated by G protein-mediated cAMP signal transduction, we hypothesized that cAMP-regulated lipolysis may be vulnerable to long-term ethanol exposure. Male Wistar rats were fed a liquid diet containing ethanol as 35% of total calories or pair-fed a control diet that isocalorically substituted maltose dextrins for ethanol for 4 wk. Lipolysis was measured by glycerol release over 1 h with or without agonists in adipocytes isolated from epididymal fat. Chronic ethanol feeding decreased beta-adrenergic receptor-stimulated lipolysis, but had no effect on basal lipolysis. In response to beta-adrenergic activation, the early peak of cAMP accumulation was suppressed after ethanol feeding, although the basal cAMP concentration in adipocytes did not differ between pair- and ethanol-fed rats. The suppression in cAMP accumulation caused by ethanol feeding was associated with increased activity of phosphodiesterase 4. Chronic ethanol feeding also decreased beta-adrenergic receptor-stimulated protein kinase A activation and phosphorylation of its downstream proteins, perilipin A and hormone-sensitive lipase, the primary lipase-mediating lipolysis. In conclusion, these data suggest that chronic ethanol feeding increased phosphodiesterase 4 activity in adipocytes, resulting in decreased accumulation of cAMP in response to beta-adrenergic activation and a suppression of beta-adrenergic stimulation of lipolysis.

Original languageEnglish
Pages (from-to)4330-8
Number of pages9
JournalEndocrinology
Volume147
Issue number9
DOIs
Publication statusPublished - Sep 2006

Keywords

  • 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors
  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone/pharmacology
  • Adipocytes/chemistry
  • Adrenergic beta-Agonists/pharmacology
  • Animals
  • Carrier Proteins
  • Cyclic AMP/analysis
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Diet
  • Epididymis
  • Ethanol/administration & dosage
  • Glycerol/metabolism
  • Isoproterenol/pharmacology
  • Lipolysis/drug effects
  • Male
  • Perilipin-1
  • Phosphodiesterase Inhibitors/pharmacology
  • Phosphoproteins/metabolism
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta/physiology
  • Sterol Esterase/metabolism

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