A model of neglect during postnatal life heightens obesity-induced hypertension and is linked to a greater metabolic compromise in female mice

Abstract

Exposure to Early Life Stress (ELS) is associated with behavioral-related alterations, increases in body mass index and higher systolic blood pressure in humans. Postnatal maternal separation and early weaning (MSEW) is a mouse model of neglect characterized by a long-term dysregulation of the neuroendocrine system. Objectives Given the contribution of adrenal-derived hormones to the development of obesity, we hypothesized that exposure to MSEW could contribute to worsen the cardiometabolic function in response to chronic high fat diet (HF) feeding by promoting adipose tissue expansion and insulin resistance. Subjects MSEW was performed in C57BL/6 mice from postnatal days 2–16 and weaned at postnatal day 17. Undisturbed litters weaned at postnatal day 21 served as the control (C) group. At the weaning day, mice were placed on a low fat diet (LF) or HF for 16 weeks. Results When fed a LF, male and female mice exposed to MSEW display similar body weight but increased fat mass compared to controls. However, when fed a HF, only female MSEW mice display increased body weight, fat mass and adipocyte hypertrophy compared with controls. Also, female MSEW mice display evidence of an early onset of cardiometabolic risk factors, including hyperinsulinemia, glucose intolerance and hypercholesterolemia. Yet, both male and female MSEW mice fed a HF show increased blood pressure compared with controls. Conclusions This study shows that MSEW promotes a sex-specific dysregulation of the adipose tissue expansion and glucose homeostasis that precedes the development of obesity-induced hypertension.

Maternal Separation Induces Long-Term Alterations in the Cardiac Oxytocin Receptor and Cystathionine γ-Lyase Expression in Mice

“…This hypothesis is supported by studies in animal models showing that MS results in cardiac changes including cardiomyocyte hypertrophy as well as cardiac fibrosis [19]. More data is available showing that MS results in changes on the vascular level by misprogramming of resistance artery smooth muscles [20], increased vasoconstriction [21], and blood pressure [22,23]. These alterations are induced by superoxide production and endothelial dysfunction [24], inflammation [25], and sensitizing of the renal and sympathetic systems [26].…”

Does early weaning shape future endocrine and metabolic disorders? Lessons from animal models

“…72 The MSEW female mice exposed to a high-fat diet (HFD) showed increased body weight, adiposity, and fasting glucose levels. 73 Moreover, these animals exhibited hyperinsulinemia, hyperleptinemia, and hypertension. 73 Therefore, MD increased the susceptibility to obesity and metabolic disorders in offspring in response to HFD, especially in female offspring.…”

The influence of psychological stress in early life on sexual maturation and sexual behavior in male and female rats

“…Neonatal psychological stress might be an independent risk factor for the development of childhood obesity in humans . This finding has also been reproduced in animal models, for example, neonatal maternal separation (MS) and early weaning‐induced hyperinsulinemia and glucose intolerance in adulthood in female mice . On the contrary, to the best of our knowledge, the effects of neonatal psychological stress on reproductive functions in later life have not been investigated in detail.…”

“…13 This finding has also been reproduced in animal models, for example, neonatal maternal separation (MS) and early weaning-induced hyperinsulinemia and glucose intolerance in adulthood in female mice. 14 On the contrary, to the best of our knowledge, the effects of neonatal psychological stress on reproductive functions in later life have not been investigated in detail. Only one study has examined the effects of neonatal psychological stress on sexual function, and it only focused on female sexual maturation/estrous cyclicity and male sexual behavior.…”