Female Mice Exposed to Early Life Stress Display Exacerbated Obesity‐Hypertension while Normal Response to Adipose Afferent Reflex Stimulation

Abstract

The experimental stimulation of afferent excitatory signals from adipose tissue has been shown to contribute with obesity‐induced hypertension as part of a mechanism called the adipose afferent reflex (AAR). Previous studies from our lab have shown that male mice exposed to maternal separation and early weaning (MSEW), a mouse model of early life stress, display increased mean arterial pressure (MAP) and sympathetic tone compared to control mice when fed a high fat diet (HF). Also, MSEW‐HF males display exacerbated blood pressure responses to the acute stimulation of the AAR in perigonadal white adipose tissue (gWAT) compared to controls that correlates with increased neuronal activation in the posterior paraventricular nucleus of the hypothalamus and rostroventrolateral medulla. We have identified increased serotonin (5‐HT) levels in eWAT from obese MSEW mice as a potential endogenous factor stimulating sensory neurons. As females MSEW do not show sympathetic activation, the aim of this study was to determine whether their increased blood pressure was independent of exacerbated blood pressure response to AAR stimulation or levels of 5‐HT in gWAT. C57BL/6J mice pups were separated from the dams from postnatal day (PD) 2 to PD 16 and weaned early on PD 17. Control (C) litters remained undisturbed with the dams and were weaned on PD 21. After weaning, Female C and MSEW mice (n=5/group) were placed on low fat diet (LF) or HF (10% and 60% Kcal from fat, respectively). At 16 weeks, subcutaneous (sc) and gWAT depots were exposed for vehicle or 1.5 pmol/μL of capsaicin (8 μL, 2’, 4 sites, bilateral). Vehicle infusions in scWAT or gWAT did not change MAP from baseline in any of the groups. Capsaicin infusions in scWAT slightly increase MAP similarly in all groups (Delta MAP, mmHg: C‐LF: 3±1; MSEW‐LF: 3±1; C‐HF: 2±1; MSEW‐HF: 2±1). In gWAT, capsaicin infusions also increased MAP similarly in all groups (Delta MAP, mmHg: C‐LF: 3±1; MSEW‐LF: 4±1; C‐HF: 3±1; MSEW‐HF: 5±2). None of these changes in MAP were significant. No differences in 5‐HT levels in scWAT (C‐HF: 1801.15±122.26; MSEW‐HF: 1799.17±216.58 ug/mg tissue) and gWAT (C‐HF: 563.51±71.41; MSEW‐HF: 518.31±99.73 ug/mg tissue); were found between groups. Furthermore, stimulation of AAR with 5‐HT (10‐6 M, 4 sites, bilateral) increased blood pressure only in male MSEW mice (p<0.05). These results suggest that the AAR is not exacerbated in obese female MSEW mice, result that is consistent with a lack of sympathetic activation compared to control mice.