Abstract
This study explored whether different ratios of fructose (F) and glucose (G) in sugar can engender significant differences in self-administration and associated neurobiological and physiological responses in male Sprague-Dawley rats. In Experiment 1, animals self-administered pellets containing 55% F + 45% G or 30% F + 70% G, and Fos immunoreactivity was assessed in hypothalamic regions regulating food intake and reward. In Experiment 2, rats self-administered solutions of 55% F + 42% G (high fructose corn syrup (HFCS)), 50% F + 50% G (sucrose) or saccharin, and mRNA of the dopamine 2 (D2R) and mu-opioid (MOR) receptor genes were assessed in striatal regions involved in addictive behaviors. Finally, in Experiment 3, rats self-administered HFCS and sucrose in their home cages, and hepatic fatty acids were quantified. It was found that higher fructose ratios engendered lower self-administration, lower Fos expression in the lateral hypothalamus/arcuate nucleus, reduced D2R and increased MOR mRNA in the dorsal striatum and nucleus accumbens core, respectively, as well as elevated omega-6 polyunsaturated fatty acids in the liver. These data indicate that a higher ratio of fructose may enhance the reinforcing effects of sugar and possibly lead to neurobiological and physiological alterations associated with addictive and metabolic disorders.
Highlights
The World Health Organization estimated that between 1980 and 2008, the rate of obesity (BMI > 30 kg/m2) doubled worldwide [1]
The 55% F + 45% G pellet was selected to approximate the ratio found in high fructose corn syrup (HFCS)-55, while the 30% F + 70% G pellet is the typical “sucrose” pellet that is employed in operant self-administration experiments
The results of Experiment 3, and other studies [78], lend support to the hypothesis [44] that frequent consumption of HFCS may be a risk factor for developing diseases that are characterized by chronic inflammatory states. These self-administration experiments in rats provide converging evidence that differences in fructose:glucose ratios can have a significant impact on self-administration behaviors
Summary
The World Health Organization estimated that between 1980 and 2008, the rate of obesity (BMI > 30 kg/m2) doubled worldwide [1]. It is clear that one important component is nutrition, with particular reference to excessive consumption of foods containing high levels of fats [13] and sugars [14,15,16] Within this context, there is the interesting issue of whether different sugars play a differential role in contributing to overeating and obesity. It is proposed that fructose may be more “hazardous” than glucose because of its limited effects on cessation of food intake and on activation of brain regions that regulate this homeostatic response [17,18,19] These observations have led to the hypothesis that sweeteners, such as high fructose corn syrup (HFCS), which contain a higher fructose to glucose ratio than sucrose, may be “addictive” and, critically involved in hedonic overeating leading to obesity [20,21,22,23]
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