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

Kang L, Nagy LE
Endocrinology. 2006 147 (9): 4330-8

PMID: 16794014 · PMCID: PMC1764504 · DOI:10.1210/en.2006-0120

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.

MeSH Terms (24)

3',5'-Cyclic-AMP Phosphodiesterases 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone Adipocytes Adrenergic beta-Agonists Animals Carrier Proteins Cyclic AMP Cyclic AMP-Dependent Protein Kinases Cyclic Nucleotide Phosphodiesterases, Type 4 Diet Epididymis Ethanol Glycerol Isoproterenol Lipolysis Male Perilipin-1 Phosphodiesterase Inhibitors Phosphoproteins Phosphorylation Rats Rats, Wistar Receptors, Adrenergic, beta Sterol Esterase

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