Sucrose induces fatty liver and pancreatic inflammation in male breeder rats independent of excess energy intake

Abstract

Fructose induces metabolic syndrome in rats; but studies have been criticized for using high concentrations of fructose that are not physiologic, for using only pure fructose, and for not controlling for energy intake. We tested the hypothesis that a 40% sucrose diet (containing 20% fructose) might induce features of metabolic syndrome in male breeder rats independent of excess energy intake. Male Sprague-Dawley breeder rats were pair fed 40% sucrose or isocaloric starch diet for 4 months and evaluated for metabolic syndrome and diabetes. In vitro studies were performed in rat insulinoma cells (RIN-m5F) exposed to uric acid, and markers of inflammation were assessed. Rats fed a 40% sucrose diet developed accelerated features of metabolic syndrome with up-regulation of fructose-dependent transporter Glut5 and fructokinase. Fatty liver and low-grade pancreatic inflammation also occurred. Uric acid was found to stimulate inflammatory mediators and oxidative stress in islet cells in vitro. Sucrose, at concentrations ingested by a subset of Americans, can accelerate metabolic syndrome, fatty liver, and type 2 diabetes mellitus in male breeder rats; and the effects are independent of excess energy intake.

Introduction

Diets enriched in fructose are known to induce features of metabolic syndrome in rats [1], [2]. However, these studies are frequently criticized for using excessive concentrations of fructose that are not physiological (eg, 60%) or for administering fructose alone (when most exposure to humans is as sucrose or high-fructose corn syrup) [3], [4]. Furthermore, there remains debate whether the effects of fructose to induce metabolic syndrome are simply a consequence of excessive energy intake [5]. Finally, whereas there are some data that added sugars may increase the risk for type 2 diabetes mellitus both experimentally [6] and in humans [7], [8], there is only minimal evidence that they have specific effects to induce islet cell dysfunction [9], [10], [11].

We therefore tested the hypothesis that a sucrose-based diet containing only 20% fructose might induce features of fatty liver and metabolic syndrome. To address whether the effects observed were specific to fructose, we administered an identical diet to control rats in which the sucrose was replaced with starch. Furthermore, all rats were pair fed so that each animal ate the exact same number of calories. To further ensure that intake was not excessive, all rats were fed approximately 90% of normal intake. The slight restriction in caloric intake is to simulate a dieting individual who still ingests a diet high in added sugars. Studies were performed in male Sprague-Dawley breeder rats, which are known to spontaneously develop features of metabolic syndrome as they age [12], [13]. Using this model system, we report that sucrose accelerated the development of metabolic syndrome and type 2 diabetes mellitus compared with starch-fed rats, in association with the development of mild inflammation in the pancreas.