THE IMPACT OF SEX ON METABOLIC AND FUNCTIONAL ABNORMALITIES, INDUCED BY HIGH-FRUCTOSE-DIET IN RATS

Abstract

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors, which manifestation may be different for men and women. Changes in sex hormone levels in men and women during lifespan contribute to increased cardiometabolic risk. Data of clinical researches suggest that transition from normal glucose tolerance to dysglycemia lead to more adverse differences in cardiometabolic risk factors in women than in men, suggesting an important impact of sex on the development of metabolic abnormalities. A significant increase in risk may be due to the sex differences in manifestation of some components of metabolic syndrome, but accurate reasons of these discrepancies need future investigations. The aim of this study was to determine the differences in impairment of glucose, lipid metabolism and cardiovascular systems function between male and female rats with different levels of estrogen sufficiency. Materials and Methods. MetS was modelled in male and female rats with different levels of estrogens by chronic (for 8 weeks) intake of fructose (high-fructose diet - HFD) with drinking water at a concentration 200 g/L. Estrogens deficiency was reproduced by bilateral ovariectomy. Experimental rats were divided into five groups: control males (n=6), control females (n=6), males with HFD (n=6), sham-operated females with intact ovaries and HFD (n=6), ovariectomized (OVX) females with HFD (n=6). Glucose homeostasis was assessed by basal glycemia, glycemia during the intra-abdominal glucose tolerance test and fructosamine level. Insulin sensitivity was determined using intra-abdominal insulin tolerance test. Body weight gain, visceral fats, level of total cholesterol, triglycerides, levels of estradiol and testosterone in blood serum were determined. At the end of the study, electrocardiograms were recorded in three standard leads from the limbs. Data are presented as mean ± standard error of mean (SEM). Results. It was established that HFD have not been induced metabolic abnormalities in female rats with intact ovaries. HFD, independently of sex, led to the development of insulin resistance and significant increase in fructosamine level in blood serum of rats. Ovariectomized females with HFD had greater intensity of body weight gain, significantly higher levels of relative mass of fats, more pronounced alterations of lipid metabolism with increased total cholesterol and significantly higher levels of triglycerides, than HFD-treated male rats. However, impairment of glucose tolerance, induced by HFD, was more pronounced in male than in OVX female rats. We found the decline testosterone levels and slight increase in estradiol levels in male rats with HFD. OVX females with HFD had a moderate significant increase in testosterone levels and dramatically decrease in estradiol concentration as result of bilateral ovariectomy. HFD, independently from sex, induced the development of sinus tachycardia in experimental animals. Metabolic abnormalities, induced by HFD, in OVX female rats led to more pronounced disturbances of heart depolarization and repolarization processes and development of diastolic dysfunction compare to HFD-treated males. Conclusions. We revealed that sex and estrogens levels have a great impact on the impairment of glucose and lipid metabolism and cardiovascular systems function, induced by high-fructose diet in rats. The obtained data justifies the necessity to take into account sex and estrogens sufficiency in the development of gender-specific prevention and treatment of metabolic syndrome.