High fat diet exacerbates adipose tissue‐derived adipokines and hypertension in female C57BL/6 mice exposed to early life stress (ELS)

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Early life stress (ELS) exposure has been recognized as an independent risk factor for obesity and cardiovascular disease. Maternal separation and early weaning (MSEW) during postnatal life show long‐lasting neuroendocrine and behavioral disturbances thereby is used as a mouse model of ELS. The goal of this study was to determine whether exposure to MSEW is associated with sex differences in adiposity, vascular function and blood pressure in response to high fat (HF) diet. MSEW was performed in C57BL/6 mice from postnatal days 2–16. Undisturbed litters served as control (C) group. Mice were placed on a low‐fat (LF, 10% kcal from fat) or HF (60% kcal from fat) diet for 16 weeks upon weaning. MSEW did not influence body weight gain in male and female mice fed a LF diet; however, MSEW increased fat mass with no changes in lean mass vs. C (p<0.05). In response to HF diet, despite significant increases in fat mass in both sexes, only female MSEW displayed higher levels of adiposity vs. C (44±2 vs. 31±2 %, p<0.05). In addition, MSEW exacerbated 24 hour mean arterial pressure (MAP) in both sexes; however, this increase in MAP was significantly greater in female (MSEW= 115.0±0.9 mmHg and C= 106.6±1.6 mmHg) than in male (MSEW= 121.2±1.3 mmHg and C=117.3±0.4 mmHg) mice (p sex<0.05, p MSEW p<0.05, p interaction <0.05). Yet, heart rate was increased only in male MSEW vs. C (p<0.05). Vascular reactivity assessed by wire myography showed increased serotonin‐induced vasoconstriction in female MSEW mice vs. C (73±15 vs. 36±3 %maximal constriction, p<0.05) but not in male MSEW mice vs. C (59±8 vs. 51±3 %maximal constriction, p<0.05). Plasma metabolic profile revealed that female, but not male, MSEW mice display hyperinsulinemia (1.3±0.1 vs. 0.5±0.1 ng/ml, p<0.05), hyperleptinemia (37.4±1.9 vs. 26.5±1.4 ng/ml, p<0.05), higher levels of plasma resistin (8.1±0.4 vs. 5.7±0.5 ng/ml, p<0.05) and PAI‐1 (1.7±0.2 vs. 0.5±0.0 ng/ml, p<0.05). Taken together, these data indicate that female mice exposed to MSEW are particularly susceptible to display fat expansion thereby increasing fat‐derived adipokines involved in vascular dysfunction and hypertension in response to HF diet.Support or Funding InformationHL111354