Secretion of high density lipoprotein by the isolated perfused alcoholic rat liver

Abstract

Summary. Chronic alcohol feeding of a low fat diet for 5 weeks led to a slightly raised though statistically non-significant high density liproprotein cholesterol/apoB containing lipoprotein cholesterol ratio in both the fasting rat serum as well as the secretory products of the isolated perfused liver.Previously published epidemiological studies have convincingly established that there is a very strong negative correlation between plasma HDL cholesterol levels and the probability (risk) of developing coronary heart disease 24 h 1 (CHD) -. T e molecu ar mechanisms underlying this protective capacity of HDL are not entirely clear. However, 2 propositionsS'Ghave been made: a) HDL may facilitate reverse cholesterol transport from cells of the artery wall and b) HDL may inhibit the uptake of LDL by cells of the artery wall. Plasma HDL levels may be influenced by dietary carbohydrates and alcohol, by physical activity, some lipid-lowering drugs and endocrine factors such as sex steroids and insulin 7. Alcohol appears to play a deleterious role with respect to cardiac muscles 8, while several recent epidemiological studies suggest a protective role for alcohol via elevation of HDL on the development of CHD 9-11. It was therefore decided to examine the capacity of an isolated perfused rat liver to secrete HDL cholesterol subsequent to chronic administration of alcohol in a totally liquid low fat (5%) Metrecal diet. Materials and methods.Male Sprague-Dawley rats originally weighing 150-175 g were fed a 37% alcohol low fat (5%) totally liquid Metrecal diet for 5 weeks as previously described 12'13. Livers from control and alcoholic rats fasted 20-24 h were perfused with recirculation for 3 h according to Lee and Hosein la. Serum samples were obtained from the inferior vena cava prior to protal vein cannulation. The lipids were extracted from the serum and cell-free perfusate with chloroform-methanol (2:1) and washed by the method of Folch et al. 14. Cholesterol was determined according to Zlatkis et al. 15. ApoB-containing lipoproteins (VLDL + LDL) were isolated by ultracentrifugation as follows: the density of the liver perfusate or rat serum was raised to 1.09 g/m116,17 using solid sodium bromide. The samples were centrifuged in a Beckman SW 56 rotor at 100,000 • g for 23 h. The float containing VLDL and LDL was quantitatively removed by suction and dialyzed extensively against saline-EDTA, pH 7.4 containing 0.02% sodium azide. The total lipids of the apoB-containing liproproteins were extracted r4 and the cholesterol content determined Is. The HDL cholesterol value was calculated by difference (total cholesterol minus apoB-containing lipoprotein cholesterol).Results. Rats maintained on the 37% low fat alcohol diet gained weight at a slower rate than their sucrose pair fed 13 _+3 (7) 9 _+2 (5) HDL/(VLDL+ LDL) ratio 4.2_+0.7 (7) 3.7_+0.6 (5)Rats were fed for 5 weeks on a 37% alcohol low fat liquid Metrecal diet and the serum samples obtained after a 20-24-h fast as described in the text. Each value represents the mean_+ ...

Ethanol Enhances De Novo Synthesis of High Density Lipoprotein Cholesterol

“…Taken together, data from this study support previous in vivo (15) and liver perfusion (16) rat studies which suggest that increased HDL lipid synthesis results from intake of dietary ethanol at 36 -37% of calories. The present study is unique, however, in elucidating a lower dose (24%) at which this ethanol effect occurs, and in providing the first in vivo experimental documen-tation that alcohol consumption specifically enhances de novo HDL nonesterified cholesterol synthesis in a nonhuman primate species with clinical relevance to man.…”