Dose-dependent effects of chronic ethanol on mouse adipose tissue lipase activity and cyclic AMP accumulation.

1. The effects of two chronic ethanol treatment schedules, which produce different plasma ethanol concentrations, on the specific activities of adipose tissue lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) have been investigated in brown and white fat. 2. Mice provided with 20% ethanol solution as sole drinking fluid for 28 days consumed between 13 and 15 g ethanol kg-1 body weight day-1 over days 22-28. The mean plasma ethanol concentration was 4.94 +/- 1.4 mM (n = 8) at 09 h 00 min on day 28 when the lipase assays were performed. Mice given ethanol in a liquid diet for 7 days consumed between 15 and 18 g ethanol day-1 over days 3-7. The mean plasma ethanol concentration was 15.9 +/- 4.7 mM (n = 8) at 09 h 00 min on day 7. These concentrations of ethanol had no effect on the activity of either LPL or HSL in vitro. 3. LPL activity in white and brown fat (expressed as nmol fatty acids released h-1 mg-1 acetone powder) was unaltered 60 min following an acute injection of ethanol (2.5 g kg-1, i.p.) which produced a mean blood ethanol level of 37.5 +/- 6.7 mM. HSL activity in white fat (expressed as nmol fatty acid released h-1 mg-1 protein) was also unaffected by this acute dose of ethanol, but the activity in brown fat was significantly reduced: 3.07 +/- 0.30 (n = 8) after ethanol compared to 4.36 +/- 0.25 (n = 12) in controls (P < 0.01). 4. LPL activity in white fat was little altered by either of the chronic ethanol treatment schedules whilst LPL activity in the brown fat from the same animals was significantly increased compared to the respective control values: 0.27 +/- 0.03 (ethanol drinking), control: 0.16 +/- 0.01; 0.79 +/- 0.14 (ethanol liquid diet), control: 0.39 +/- 0.05. 5. HSL activity in white fat was significantly increased by the chronic drinking treatment (7.7 +/- 0.5; control: 3.78 +/- 0.17, n = 8) at the same time that the activity in brown fat was reduced (3.76 +/- 0.2; control: 4.74 +/- 0.16). The ethanol liquid diet also reduced HSL activity in brown fat but had negligible effect in white fat. 6. The effects of the two chronic ethanol treatments on adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in brown and white fat were very similar, both qualitatively and quantitatively, to the effects on HSL. 7. It has been shown that brown and white adipose tissues respond differently to the presence of chronic ethanol and that the response is dependent both upon the concentration of ethanol and the nature of the diet with which the ethanol is administered. The effects of ethanol on adipose tissue HSL activity appear to be mediated via changes in the tissue cyclic AMP level and, in this respect, brown fat is more sensitive to ethanol than white fat.