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

• Published in: International Journal of Obesity Vol. 42; no. 7; pp. 1354 - 1365
• Main Authors: Murphy, Margaret O., Herald, Joseph B., Leachman, Jacqueline, Villasante Tezanos, Alejandro, Cohn, Dianne M., Loria, Analia S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2018; Nature Publishing Group
• Subjects: 13/105; 13/21; 14/63; 38/77; 59/57; 631/1647/334/1874/345; 631/443/319/1642/2037; 64/60; 9/10; Adipose tissue; Adipose Tissue - metabolism; Adiposity - physiology; Analysis; Animals; Blood pressure; Body fat; Body mass index; Body size; Body weight; Complications and side effects; Diet; Diet, Fat-Restricted; Diet, High-Fat; Disease Models, Animal; Displays (Marketing); Epidemiology; Exposure; Glucose; Glucose intolerance; Glucose tolerance; Health Promotion and Disease Prevention; Health risks; High fat diet; Homeostasis; Hormones; House mouse; Hypercholesterolemia; Hyperinsulinemia; Hypertension; Hypertension - etiology; Hypertension - physiopathology; Hypertrophy; Insulin; Insulin resistance; Internal Medicine; Intolerance; Low fat diet; Maternal Deprivation; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred C57BL; Neuroendocrine system; Nutrient deficiency; Obesity; Obesity - complications; Obesity - physiopathology; Public Health; Risk analysis; Risk assessment; Risk factors; Rodents; Stress (Psychology); Type 2 diabetes; Weaning
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/s41366-018-0035-z

. 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  the worsening of 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.