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Hepatic fatty acid profile in the rat model of NAFLD: influence of sex and diet

Nonalcoholic fatty liver disease (NAFLD) is an important health disorder with the increasing incidence in Western countries. High-fructose and cafeteria diet rodent models have been important source of data on the pathophysiological mechanisms of NAFLD. Therefore, our aim was to investigate the differences in the hepatic fatty acid profile and the influence of diet and sex in these models. Thirty-six Wistar rats (18 male and 18 female) were divided into the control group (CON), the high fructose group (HF, 15% of fructose in the drinking water) and the cafeteria diet group (CAF, 50% basal diet and 50% cafeteria diet). All dietary treatments lasted for 20 weeks. Liver histopathology was assessed by H&E, PAS and Oil red staining, lipid peroxidation was assessed by measuring MDA-TBARS and 4-HNE and the expression of the inflammation gene markers was quantified by RT- qPCR. The analysis of the hepatic fatty acid composition was performed using gas chromatography after the lipid extraction and methylation. For statistical data analysis, GraphPad 8 was used. Data were compared using the analysis of variance and Tukey post hoc test. The rats from both treated groups showed histological evidence of NAFLD including lipid accumulation and increased glycogen accumulation. The expression of the inflammation gene markers (TGFβ and IL6) significantly increased. Markers of lipid peroxidation were also increased (MDA-TBARS and 4-HNE). Hepatic fatty acid profile showed significant variations depending on the diet and sex. In general, in treated rats significant increase in monounsaturated fatty acids and decrease in n3 and n6 polyunsaturated fatty acids (PUFA) was visible. In the cafeteria diet, the depletion of PUFA was much stronger. The concentration of eicosapentaenoic acid was drastically reduced in the hepatic phospholipids and triglycerides and docosahexaenoic acid concentration were much lower in the cafeteria diet compared to the high-fructose group. Palmitoleic acid concentration increased in the high-fructose group, while in the cafeteria group concentrations remained unchanged. In both diets, the concentration of n6 docosapentaenoic (n6 DPA) acid increased. Sex also had significant influence on the fatty acid profile. Overall concentrations of n3 fatty acids and n6 DPA concentration were higher in the female rats. Most of the sex related changes were also visible during NAFLD. Nevertheless, several fatty acids showed NAFLD x sex interactions (e.g. C20:3n6 and C16:1n7) The results showed significant differences in the hepatic fatty acid profile in investigated rat models of NAFLD. The observed differences include fatty acids with important biological effects (e.g. n3 PUFA), which, therefore, must be considered in the investigations of NAFLD.

NAFLD ; Lipids ; Fatty acid ; Fructose ; Cafeteria diet

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