The effect of age on hypothalamic oxidative stress in fructose-induced metabolic syndrome.

Sevtap Han1, Bora Palabiyik1, Nur Banu Uzun1, Merve Yilmaz1, Orhan Uludag1, Bilgen Basgut2. 1Gazi University, Faculty of Pharmacy, Department of Pharmacology 06330, Turkey, 2Eastern Mediterranean University, Faculty of Pharmacy, Pharmacology Unit, Turkey

Metabolic syndrome is a complex pathology associated with hypertension, dyslipidemia, insulin resistance and obesity. It results from over ingestion and sedentary lifestyle and high fructose containing diet induces the disorders in metabolic syndrome. It’s well known that the incidence of metabolic syndrome is higher in elderly. Both age related hypertension and obesity have been linked to increased oxidative stress and sympathetic activity. Therefore, we investigated the effects of age on hypothalamic oxidative stress in high fructose induced metabolic syndrome.

Young (4 mo, n=8) and old (24 mo, n=8) male Wistar albino rats were fed with standard chow or 20% fructose diet for 6 weeks. Blood pressures were measured by using tail-cuff method during the diet regimen. Also we measured biochemical parameters in the blood samples as fasting glucose, TG, and HDL levels. Oral glucose tolerance test was administrated at the end of the fructose diet duration. After the experimental protocol, rats were sacrificed and hypothalamic tissues were dissected. The mRNA levels of NADPH subunits: gp91 phox and p22 phox (oxidative stress markers); antioxidant enzymes: CuZnSOD, MnSOD and catalase were measured by real-time PCR. For statistical analysis student-t test was used. For all comparisons, differences were considered statistically significant at a p<0.05.

We found that the systolic blood pressures (SBP) increased with age, with a further increment in SBP due to the fructose diet. While the plasma glucose levels decreased with age, fructose diet caused a significant increase in glucose levels in the old rats. TG levels increased in response to fructose diet in both age groups, this increment was significantly higher in the old group than young. Furthermore, oral glucose tolerance impaired with age and due to fructose diet only in old rats. Although hypothalamic NADPH oxidase associated mRNA levels (gp91 phox, p22 phox) increased with age, yet remained unaltered with the fructose diet. However, catalase mRNA levels decreased with age and significantly increased in old fructose group. MnSOD and CuZnSOD levels were unchanged with age. High fructose diet significantly decreased MnSOD levels in old rats. In brief, our results showed that high-fructose intake did not change hypothalamic oxidative stress markers in young rats but it changed the central oxidant/antioxidant balance in old rats.

These results suggest that central mechanisms might be mediate predisposition of metabolic syndrome especially in terms of biochemical markers in the elderly. Although in young rats peripheral mechanisms rather than central ones plays an important role in development of metabolic syndrome.