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 language | English |
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Pages (from-to) | 4330-8 |
Number of pages | 9 |
Journal | Endocrinology |
Volume | 147 |
Issue number | 9 |
DOIs | |
Publication status | Published - 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