Influência da dieta rica em frutose sobre a hiperalgesia e comportamento doentio em ratos

Abstract

The increased intake of processed foods and products such as soft drinks, sweetened drinks and corn syrup containing high concentration of fructose can cause metabolic disorders such as obesity, insulin resistance, type 2 diabetes mellitus and cardiovascular disease in humans. These disorders may alter the immune response of these individuals. The objective of this study was to investigate the inflammatory hyperalgesia and sickness behavior after an immune challenge in animals with metabolic disorders induced by diet rich in fructose. Adult male Wistar rats were provided either water or a fructose solution (10%) for 5 weeks. Peripheral inflammatory hyperalgesia according to the Von Frey test were evaluated after stimuli with carrageenan, lipopolysaccharide (LPS) and prostaglandin E2 (PGE2). Sickness behaviors were assessed 2 h following the injection of either a lipopolysaccharide (LPS) or vehicle. The rats were subjected to an open field test, a social interaction test, a food intake test and a fever evaluation. Cytokine expression was assessed in both adipose tissue and hypothalamus samples. The neural response was assessed in the forebrain via immunohistochemistry for c-Fos. Compared with the control group, the fructose diet induced dyslipidemia and significantly higher plasma glucose levels as well as both epididymal and retroperitoneal adiposity and insulin resistance. Increased peripheral inflammatory hyperalgesia were observed in animals treated with fructose. Furthermore, in response to LPS, the rats subjected to a fructose diet exhibited exacerbated sickness behaviors and accentuated febrile responses. Larger increases in cytokine expression were observed in both the hypothalamus and the adipose tissue of the obese rats compared with the control rats in response to LPS. LPS induced Fos protein expression in several areas of the brains of the control rats; however, larger numbers of Fos-positive cells were observed in the brains of the rats that were fed a fructose diet. In this study we conclude that the high-fructose diet plays an important role in the induction of metabolic disorders which will enhance inflammatory hyperalgesia and sickness behavior in response to an immune challenge induction via cytokines in the hypothalamus.