Fructose supplementation worsens the deleterious effects of short‐term high‐fat feeding on hepatic steatosis and lipid metabolism in adult rats

New Findings What is the central question of this study? In humans, ‘Western‐style’ diet is characterized by high levels of both saturated fats and fructose. Lipid oversupply to the liver typical of high‐fat diets could be exacerbated by the coexistence of high levels of fat and fructose in the diet, thus accelerating the development of metabolic deregulation. What is the main finding and its importance? Short‐term consumption of a Western diet, rich in saturated fats and fructose, is more conducive to the development of liver steatosis and deleterious to glucose homeostasis than a high‐fat diet. This result points to the harmful effect of adding fructose to the usual Western, high‐fat diet. The purpose of the present study was to examine the short‐term effect of high‐fat or high‐fat–high‐fructose feeding on hepatic lipid metabolism and mitochondrial function in adult sedentary rats. Adult male rats were fed a high‐fat or high‐fat–high‐fructose diet for 2 weeks. Body and liver composition, hepatic steatosis, plasma lipid profile and hepatic insulin sensitivity, together with whole‐body and hepatic de novo lipogenesis, were assessed. Hepatic mitochondrial mass, functionality, oxidative stress and antioxidant defense were also measured. Rats fed the high‐fat–high‐fructose diet exhibited significantly higher plasma triglycerides, non‐esterified fatty acids, insulin and indexes of hepatic insulin resistance compared with rats fed a low‐fat or a high‐fat diet. Hepatic triglycerides and ceramide, as well as the degree of steatosis and necrosis, were significantly higher, while liver p‐Akt was significantly lower, in rats fed high‐fat–high‐fructose diet than in rats fed high‐fat diet. A significant increase in non‐protein respiratory quotient and hepatic fatty acid synthase and stearoyl CoA desaturase activity was found in rats fed the high‐fat–high‐fructose diet compared with those fed the high‐fat diet. Significantly lower mitochondrial oxidative capacity but significantly higher oxidative stress was found in rats fed high‐fat and high‐fat–high‐fructose diets compared with rats fed low‐fat diet, while mitochondrial mass significantly increased only in rats fed high‐fat–high‐fructose diet. In conclusion, short‐term consumption of a Western diet, rich in saturated fats and fructose, is more conducive to the development of liver steatosis and deleterious to glucose homeostasis than a high‐fat diet.