Dietary manipulation and stress alter hepatic fat metabolism in rats

Fatty liver is commonly observed in a number of disease slates (i.e. obesity, diabetes, critical illness) which predispose the greatest risk for infectious complications. Yet, it is currently impossible to manipulate the degree of liver fat content under normal conditions which would allow the study of the effects of hepatic steatosis on morbidity and mortality. We investigated the effects of diet composition and starvation on hepatic fat metabolism in male Wistar rats (325-350g). Liver weights, liver triglycéride (TG) content, and serum alkaline phosphatase (A<(>) were measured in response to dietary manipulation. Three groups of rals (n = 10) had free access to either a regular chow (55% of total energy as carbohydrate (CHO), 14% fat (F), and 31% protein (P)), a high-fat diet (40% CHO, 40% F, and 20% P), or a high-carbohydrate diet (81% CHO, 4% F, and 15% P) for six days. Another three groups (n = 10) of animals were starved for 48h prior to the dietary manipulation. Daily food intake and body weights were recorded, Results were analyzed by one-way ANOVA with Bonferroni's correction for significant differences (p<0.05). Without prior starvation, liver weights in the high-CHO group were significantely higher (16.2 ±1.6 g) than in the control group (14.4 ±1.3 g). The high-fat diet had no influence on liver weights (15.1 ±1.3 g). Liver triglycéride content was highest (p<0.05) in response to the high-fat diet (25.6 ±6.9 mg/g) and not different from the control group (9.4 ±3.8 mg/g) in rats on the high-CHO diet (12.4 ±3.7 mg/g). Serum A(|> was significantely elevated in response to both experimental diets. Upon refeeding after 48h of starvation, liver triglycéride contents were significantely elevated in both, the high-fat (18.8 ±8.3 mg/g) and the high-CHO group (28.7 ±14.4 mg/g) compared to the starved control group (6.7 ±3.7 mg/g). Liver weights were not different in the three groups. Serum A<|> was elevated in the high-fat group (p<0.05) but not in the high-CHO group. In summary, the high-fat diet alone induced an increase in liver TG-content while the high-CHO diet did not. With the addition of stress due lo starvation, however, the highCHO diet caused a significant increase in liver fat content. We conclude that diets alone can manipulate hepatic fat metabolism and the response changes with stress. Further, dietary manipulation can serve as a model for the direct investigation of the role of hepatic steatosis on clinically important parameters such as the ability of the liver to clear and detoxify inflammatory mediators, and the capacity of the liver to handle increased fat loads or to manufacture constitutive proteins.