# Short- and Long-Term Effects of Undernutrition During Adolescence on Oxidative Status and Glucose Homeostasis in Male and Female Rats

## TL;DR

Undernutrition during adolescence leads to long-term metabolic issues in rats, including obesity and disrupted redox balance, especially in males.

## Contribution

The study reveals sex-specific long-term effects of adolescent undernutrition on glucose homeostasis and oxidative stress in rats.

## Key findings

- Short-term undernutrition increases insulin sensitivity and lean phenotype in both male and female rats.
- Long-term undernutrition leads to obesity and high insulin sensitivity in both sexes, but only males show impaired iBAT redox status.
- Male rats exhibit reduced CAT activity and increased GSH levels in iBAT after long-term undernutrition.

## Abstract

Undernutrition, particularly in critical stages of life development, such as adolescence, can lead to lifelong energy and glucose dyshomeostasis. When dietary protein is inadequate during adolescence, it has long-term consequences in male rats, leading to an obesity phenotype associated with insulin resistance and hypothalamus-pituitary-gonadal axis and testosterone disruption. Accordingly, this study was designed to evaluate both the immediate (short-term) and extended (long-term) effects of undernutrition resulting from food deprivation (by restricting caloric intake to 50% of that consumed by the control group of rats) on body composition, glucose–insulin homeostasis and redox balance markers in metabolic (liver) and thermogenic interscapular brown adipose (iBAT) tissues in both male and female rats. The body of data in the present article provides novel information for the scientific community, namely, that calorie deprivation during adolescence causes in the short term a lean phenotype and increased insulin sensitivity (in both male and female rats), whereas in the long term it causes an obese phenotype and high peripheral insulin sensitivity in both male and female rats, while in male rats, it causes impaired iBAT redox status (reduced SOD and CAT activity and increased GSH levels).

Malnutrition during adolescence can cause metabolic diseases later in life. This study examined the short- and long-term effects of undernutrition during adolescence on body composition, glucose homeostasis and redox balance. Male (n = 32) and female (n = 32) Wistar rats were fed a rodent chow reduced by 50% (FR50) of the amount consumed by control rats (CONT) from 30 to 60 days and then fed ad libitum until 120 days of age. Half of the rats were euthanized at 60 and the other half at 120 days old. At 60 and 120 days old, glucose and insulin tolerance test; skeletal muscle, visceral fat, liver and interscapular brown adipose tissue (iBAT) weights; and oxidative stress marker levels in the liver and iBAT were evaluated. The FR50 male (FR50-M) and female (FR50-F) rats exhibited a lean phenotype and high insulin sensitivity at 60 days of age (p < 0.05), but at 120 days of age, they exhibited an obese phenotype with high insulin sensitivity (p < 0.05). An increase in liver GSH was observed as only a short-term effect (p < 0.05). At 120 days of age, only male rats displayed increased iBAT GSH levels (p < 0.05) and reduced CAT activity (p < 0.01). In summary, undernutrition during adolescence affects body composition, glucose homeostasis and redox status equally in males and females but causes long-term impairment of the redox status of iBAT only in male rats.