The differential effect of fructose on metabolic risk factors

Abstract

High fructose intakes have previously been associated with dysregulation of carbohydrate and lipid metabolism within the liver. This dysregulation of metabolism can produce a distinctive phenotype that includes fatty liver, insulin resistance and dysregulated lipid transport. Although the association between fructose consumption and disease has yet to be elucidated, this phenotype is associated with metabolic-related diseases such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Newly emerging research suggests that previous long-term exposure to fructose may result in metabolic adaptations to create a new steady state, thereby providing a protective effect against bolus doses of fructose. The objective of this study was to determine if previous exposure to fructose can alleviate symptoms of metabolic distress such as weight gain, high liver weight and blood metabolomics. To achieve this objective, adult sexbalanced C57Bl/6J mice consumed a high-fat, high-sugar, hypercaloric diet consisting of either 0%, 10%, or 20% of total calories from fructose. In the preliminary study, the 20% fructose group returned to chow diet after 2-weeks to examine if metabolic adaptations are possible after a short time interval. Prior to necropsy, 0.5 g/kg U-C¹³-fructose (stable isotope) and 0.5 g/kg glucose were orally gavaged. After 30 minutes, the mice were sacrificed by heart puncture and all samples were collected and flash frozen. Previous fructose exposure was associated with a higher enrichment of glucose from ¹³C-fructose, specifically in females. Other sex-related differences were also present including liver weight, fatty acid profile, and triacylglycerol content, suggesting that oral fructose alters metabolic outcomes in a sex-dependent manner in mice.