Age-related features of developing insulin resistance and adipocyte sensitivity to insulin in rats with induced metabolic syndrome

Abstract

Old age and insulin resistance accompanying metabolic syndrome are significant factors in the development of cardiovascular pathology.Aim. The aim of the study was to identify the age-related characteristics of developing insulin resistance on the body level and insulin resistance in rat adipocytes in animals with induced metabolic syndrome.Material and Methods. The study was carried out on male Wistar rats, which were divided into the following groups: group 1 (n = 14) comprised intact rats aged 150 days at the end of study; group 2 (n = 14) comprised rats aged 150 days at the end of 90-day period on diet with high contents of carbohydrates and fats (HCHFD); group 3 (n = 14) comprised intact rats aged 540 days at the end of the study; group 4 (n = 14) comprised rats aged 540 days after the end of 90-day HCHFD. Diet composition was as follows: 16% proteins, 21% fats, 46% carbohydrates including 17% fructose, 0.125% cholesterol, and replacement of drinking water with a 20%-fructose solution. At the end of the diet, body and organ weights were measured, and contents of glucose, insulin, triglycerides, serum leptin, and liver triglycerides were assessed. Epididymal adipose tissue adipocytes were isolated enzymatically. The content of reactive oxygen species (ROS) was investigated using 2,3-dihydrodichlorofluorescein diacetate. Increased ROS production and lipolysis inhibition in response to insulin were observed.Results. The signs of metabolic syndrome were observed in both age groups of HCHFD animals and included visceral obesity, hyperglycemia, and insulin resistance measured by homeostatic model assessment of insulin resistance (HOMA-IR). However, the obesity indicators were more pronounced in the group of young rats, whereas the signs of insulin resistance prevailed in older rats. Leptinemia directly correlated with HOMA-IR (rSp = 0.485, p = 0.03). Insulin resistance of adipocytes was observed in rats older than 540 days after the HCHFD.Conclusion. The obtained results suggested that age was a risk factor for the development of insulin resistance on the body level. Aging resulted in a decrease in the adipocyte sensitivity to insulin in metabolic syndrome. An increase in leptin may be a possible mechanism for worsening of insulin resistance with age.