Changes in liver weight are independent of hepatic lipid content in guinea pigs fed a high‐cholesterol low‐carbohydrate diet

Abstract

We have used high cholesterol (HC) diets to study mechanisms of atherosclerosis in the guinea pig and shown that low carbohydrate diets (LCD) mitigate aortic cholesterol accumulation and inflammatory expression. We have also shown that HC diets induce fatty liver in guinea pigs. We evaluated whether LCD could improve hepatic steatosis in guinea pigs. Male Hartley guinea pigs were fed a HC diet (0.25g/100g) and randomly assigned (n=10/group) to consume either a LCD or high‐carbohydrate diet (HCD) for 12 wk. Plasma and whole livers were collected for lipid analysis. Plasma LDL cholesterol was lower in animals fed the LCD (P < 0.01) diet while plasma triglycerides (TG) were higher (P < 0.05). There were no differences in plasma free fatty acids or plasma glucose between groups. However, glucagon‐like peptide‐1 (GLP‐1) was lower in the LCD group (P < 0.01). Liver weight was 40% higher in the LCD compared to the HCD group. Interestingly despite the increased liver weight in LCD there were no differences in hepatic TG, cholesterol or non‐esterified fatty acids between groups. Histological analysis performed by hematoxylin and eosin staining confirmed there were no differences in hepatic lipid accumulation or steatosis between groups. Collectively these results suggest that in the presence of a HC‐LCD, the increase in liver mass is unrelated to lipid accumulation. An increased number of hepatocytes through an accelerated regenerative process may be responsible for these observations in the LCD group.