Short Exposure to a High-Sucrose Diet and the First 'Hit' of Nonalcoholic Fatty Liver Disease in Mice.

ABSTRACT

High-sucrose and high-fat diets induce deregulation in the metabolism of lipids and carbohydrates. This study aimed to detect the initial consequences on lipogenesis, gluconeogenesis and insulin signaling in the livers of rodents fed high-fat and/or high-sucrose diets for a short period of time. Male mice received a standard chow (SC), high-fat (HF), high-sucrose (HSu) or high-fat, high-sucrose (HFHSu) diet for 4 weeks. At euthanasia, blood was collected and the liver was removed for histomorphometrical and molecular analysis. The HF, HSu and HFHSu groups presented glucose intolerance, hepatomegaly, liver steatosis and lipid profile alteration when compared to the SC group (p < 0.0005). Additionally, there was an elevation in protein levels involved in lipogenesis (SREBP-1c), gluconeogenesis (PEPCK and G6Pase) and insulin signaling (IRS-1 and Akt) in the livers from the experimental groups compared to the SC group (p < 0.0005). Thus, we conclude that a short-term HF and/or HSu diet promotes glucose intolerance and liver damage in adult male mice. Surprisingly, the short exposure to excess sucrose in the diet promoted glucose intolerance and liver damage even in the absence of an increase in body mass or changes in serum insulin, cholesterol and triacylglycerol levels.