Acipimox Induces the Hepatic Accumulation of Long‐Chain Diacylglycerides and Triglycerides in Severely Burned Sprague Dawley Rats

Abstract

ObjectivePersistent lipolysis is a hallmark of severe burns, contributing to futile triglyceride cycling and the accumulation of lipid in ectopic tissues. It has been suggested that the administration of acipimox, a potent inhibitor of lipolysis, may blunt the hypermetabolic response to burns. However, what impact massive burns has on the accumulation of individual lipid species in the liver and how this is affected by acipimox treatment is unknown.HypothesisWe hypothesize that large burns results in the accumulation of lipotoxic species within the liver and that this can be prevented by administering acipimox.MethodsThirty‐two male Sprague Dawley rats were randomized to receive either a scald burn (~60% total body surface area) or sham procedure, performed under isoflurane general anesthesia. Afterwards, animals were further randomized to receive either acipimox (50 mg/kg/day) or vehicle (saline) by i.p. injection administered once a day for 7 days. On day 7, animals were euthanized and the liver snap frozen in liquid nitrogen. Liver lipids were extracted by using a chloroform:methanol (2:1) solution and diacylglycerol (DAG), triacylglycerol (TAG), free fatty acids (FFA) and cholesterol esters (CE) separated by thin‐layer chromatography. Afterwards, individual lipid classes were esterified to methyl esters, derivatized using heptane, and analyzed by gas chromatography (GC). The fatty acids C16:0, C18:0, cis/trans C18:1, cis 18:2, C20:0, C22:0, C24:0, and C22:6 were resolved by GC for each of the lipid classes examined.ResultsLiver weights were comparable between groups. Burn injury had no significant effect on the concentration of liver lipids compared to sham treated animals, irrespective of lipid class (P > 0.05). In contrast, the administration of acipimox significantly increased liver C16:0 (2.1‐fold; P < 0.05), trans C18:1 (2.5‐fold; P < 0.05), and cis C18:2 (5.5‐fold; P < 0.05) TAG content in burned animals, when compared to injured animals treated with vehicle. No effect of acipimox on liver lipids was observed in sham treated animals.ConclusionContrary to expectations, acipimox causes the accumulation of long‐chain TAGs in rat liver following massive burns, but this is not observed in response to burn injury alone. The ability of acipimox to cause unwanted hepatic metabolic side effects warrants further investigation before it is used clinically to treat massive burns.