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

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. 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. 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. 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. 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.