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 journalArticlepeer-review

    26 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 - Sept 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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