Cholesterol metabolism in rat adrenal gland during reversible endotoxic shock

Abstract

The adrenal glands have a crucial role for survival during endotoxic shock. Cholesterol is the obligatory intermediary in corticosteroid biosynthesis; thus any alteration in either the availability of cholesterol or in the ability of the adrenal gland to use cholesterol would have a profound effect on corticosteroid production. We have studied the effect of Escherichia coli endotoxin on cholesterol metabolism, injecting lipopolysaccharide (1.6 mg/100 g body) from E. coli 0111:B4 into the tail vein of male Wistar rat. Previous studies from this laboratory have shown that this dose of lipopolysaccharide induces a reversible endotoxic shock. During reversible endotoxic shock there is an alteration in plasma cholesterol; plasma total-cholesterol levels increase mainly at 6-24 h post-lipopolysaccharide injection, whereas cholesterol in high-density lipoproteins shows no significant variations, except a slight but significant decrease at 24 h. The cholesterol content in adrenal gland is diminished in endotoxemic rat, this decrease is more important at 6-24 h after endotoxin injection. We have also measured the acyl-CoA:cholesterol O-acyltransferase (ACAT) and cholesterol-esterase (CEH) activity during endotoxic shock. ACAT activity decreases after lipopolysaccharide injection. ACAT activity in endotoxemic rats is approximately 35-40% of the activity in control rats. This decrease is due to a defect in the functional capacity of the enzyme, since with exogenous cholesterol there is no significant variation in the ACAT activity. CEH activity, in contrast, increases during endotoxic shock; it shows a maximum (twofold the activity seen in control rats) at 6 h after lipopolysaccharide injection. These results show that lipopolysaccharide injection modifies cholesterol metabolism in plasma and in the adrenal gland, either directly or by mediators.

Liver X Receptor α Activation with the Synthetic Ligand T0901317 Reduces Lung Injury and Inflammation After Hemorrhage and Resuscitation Via Inhibition of the Nuclear Factor κB Pathway

“…In support of this hypothesis, a previous study by Daull et al (32) showed a similar elevation of plasma cholesterol during the immediate resuscitative period following autologous blood transfusion amongst rats subjected to hemorrhage and resuscitation. Furthermore, a study by Abarca et al (33) also showed an increase in plasma cholesterol levels of rats during the early phase of reversible circulatory shock induced by endotoxin injection.…”

Serum Lipids and Lipoproteins During Uncomplicated Malaria: A Cohort Study in Lambaréné, Gabon

“…Several theories have been described in detail before. 7 In patients with acute infection [57][58][59][60][61][62] or with severe sepsis, lipid concentrations can occur rapidly (D0) and can decrease to 50% of the recovery concentrations. 23 HDL-C is found to decrease in patients with sepsis, but not as extreme as found in malaria patients in this study.…”

Effects of endotoxin on lipid metabolism

“…In rodents the increase in serum cholesterol is delayed in onset compared with the increase in serum triacylglycerols and is primarily due to an increase in LDL cholesterol [9,20,21]. In Syrian hamsters there is an increase in free cholesterol with only a modest increase in esterified cholesterol [22].…”

“…Endotoxin decreases HDL cholesterol levels in both primates and non-primates [2,7,9,20,22], This decrease is both rapid (3-4 h) and sustained (24 h) [20,22]. A decrease in cholesterol ester is responsible for the decreased HDL cholesterol as endotoxin increases free cholesterol [3,22].…”