Metabolic status of adipose tissue after fructose overconsumption – differences between young and adult female rats

Abstract

Modern diet, rich in refined sugars and sweeteners, led to dramatic increase in fructose intake especially in young population. Excessive fructose intake has been associated with growing rate of obesity, insulin resistance and development of metabolic syndrome, women being more prone than men. Chronic low-grade inflammation accompanies obesity and has been implicated in the pathogenesis of obesity-related disorders including metabolic syndrome and insulin resistance. To elucidate whether fructose overconsumption causes inflammation in the visceral adipose tissue (VAT) of young and adult female rats thus contributing to the development of obesity and insulin resistance. We investigated the effects of 9-week fructose-enriched diet applied immediately after weaning (young) or at the 2.5 months of age (adult) on nuclear factor κB (NF-κB) intracellular distribution, and on the expression of pro-inflammatory cytokines (IL-1β, IL-6 and TNFα) in female Wistar rats. Additionally, insulin signalling was analysed at the level of insulin receptor substrate-1 (IRS1), Akt kinase, and their activating and inhibitory phosphorylations. Fructose-enriched diet increased absolute and relative VAT mass in young female rats. There were no changes in VAT mass of adults after fructose diet, even though histological analysis revealed the presence of islets of smaller adipocytes, which indicated adipogenesis. Both young and adult female fructose-fed rats had increased nuclear accumulation of NF-κB and elevated expression of pro-inflammatory cytokines in the VAT. In adults, fructose overconsumption reduced protein content and stimulatory phosphorylation of Akt kinase, while increasing inhibitory phosphorylation of IRS-1. These changes were not observed in young female rats. The results suggest that fructose-enriched diet causes inflammation in VAT of both young and adult female rats. Our work supports the stand that VAT inflammation could represent one of the earliest metabolic perturbations upon fructose overconsumption, since it can occur even before the onset of obesity or insulin resistance. Additionally, only adults developed VAT insulin resistance, indicating age-dependent differences in insulin signalling system and its response to fructose overconsumption in female rats.