Postnatal overnutrition and undernutrition and immunometabolic markers in mice during adulthood

Abstract

According to the metabolic programming hypothesis, nutritional changes in the neonatal period may influence physiological processes with repercussions in adulthood, inducing or preventing the development of immunometabolic changes and, consequently, the genesis of chronic diseases. The aim of this study was to evaluate the influence of postnatal overnutrition and undernutrition on metabolic and inflammatory markers during adulthood. Female C57BL / 6 female mice were mated over a period of 10 days. After birth, the litters size was relocated for the lactation period, obtaining the experimental groups: control (C) with the standard litter of 8-10 pups, undernutrition (UN) with the litter increased to 15-16 pups and overnutrition (ON) with the litter reduced to 3-4 pups. Only male pups were used in the study, and the process described above was repeated until the desired number of animals was obtained for the experimental groups (C = 8; ON = 8; UN = 6). After weaning, which occurred at 21 days of age, the animals were kept with free access to water and standard chow. Body weight and food intake were measured weekly. Mice were euthanized at 120 days of age for tissue collection. Biochemical analyzes were performed using commercial kits. Concentrations of serum adipokines, as well as cytokines in the epididymal adipose tissue were determined by ELISA. Hepatic lipids were extracted by the Folch method and subsequently evaluated by commercial kits. Oxidative stress markers (TBARS and hydroperoxide concentration) and antioxidant enzymes (SOD and CAT) were determined using a colorimetric method. Statistical analyzes were performed using the GraphPad Prism®, and the comparison between groups was done using the Student’s t test. The level of significance adopted was P <0.05. The ON model induced higher body weight at 21 and 120 days of life, as well as higher liver and epididymal adipose tissue weight. While the UN model presented lower body weight at 21 days, lower Lee index and epididymal adipose tissue weight at 120 days. In biochemical parameters, the ON model presented higher serum concentrations of glucose, total cholesterol and LDL-cholesterol and increased hepatic triacylglycerol. The UN model exhibited higher serum LDL-cholesterol and triacylglycerol concentrations, lower HDL-cholesterol concentration, and higher hepatic triacylglycerol concentration. In hepatic oxidative stress, both experimental groups presented higher concentrations of TBARS and hydroperoxides; also, reduction in catalase activity. Both groups presented higher concentration of TNF-α in the epididymal adipose tissue. Regarding serum adipokines, the ON group showed an increase in resistin and leptin concentrations, while the UN group showed an increase in leptin and a reduction in resistin, chemerin and adiponectin concentrations. Thus, both experimental models induced persistent metabolic and inflammatory changes in adulthood, increasing the risk of developing metabolic diseases.