Effects of acipimox on the secretion of adipokines, the composition of fatty acids, and development of non-alcoholic fatty liver disease in rats fed a high-fat diet

Abstract

Acipimox, a lipolysis inhibitor, has been reported to improve insulin resistance by lowering plasma FFA. Recently, the role of n-3 and n-6 fatty acids in regards to insulin resistance was focused on. However, there was no adequate study of the acipimox effects on the composition of fatty acids. In addition, little is known about whether acipimox can improve development of fatty liver disease. At 8 weeks of age, male Sprague-Dawley rats weighing approximately 280g were randomly assigned to one of three treatment groups (standard diet, high-fat diet with vehicle, high-fat diet with acipimox). After 4 weeks, we performed an intraperitoneal insulin tolerance test and measured fatty acids composition in addition to adipokines. Changes in liver histopathology were examined using hematoxylin and eosin, Oil red O, and tumor necrosis factor-α staining. There were no differences between the three groups in basal body weight and food intake. Body weight increment was higher in rats fed a high-fat diet without difference by acipimox administration. The plasma level of leptin tended to increase in the high-fat diet group and to decrease by acipimox. Adiponectin levels tended to decrease in plasma of the high-fat diet group and to increase by acipimox. Insulin sensitivity decreased in rats fed a high-fat diet and appeared to be improved by acipimox administration. Although acipimox showed conflicting results in changes of fatty acids composition, it induced improvement in the degree of steatosis and inflammation of the liver. These results suggest that acipimox might yield beneficial effects on the development of non-alcoholic fatty liver disease (NAFLD) and be a new therapeutic strategy. Further studies are required for the effects of acipimox on NAFLD development and the underlying mechanisms.