Abstract 138: Acute Stimulation of Neuro-Adipose Connections Increase Blood Pressure Responses in Male Mice Exposed to Early Life Stress

Abstract

Visceral adiposity increases sympathetic activation and the risk for obesity-induced hypertension. Experimental stimulation of afferent excitatory signals from adipose tissue contributes to increased sympathetic activation during obesity-induced hypertension as part of a sympatho-excitatory mechanism called the Adipose Afferent Reflex (AAR). Our lab has shown that male mice exposed to maternal separation and early weaning (MSEW), a mouse model that mimics early life stress in humans, display increased sympathetic tone and mean arterial pressure (MAP) when fed high fat diet chronically. Therefore, we hypothesize that the AAR could be implicated in the exacerbated obesity-induced hypertension observed in male MSEW mice. Litters were separated from the dam from postnatal days 2 to 16 and weaned early on day 17. Undisturbed controls (C) were weaned on day 21. After weaning, C and MSEW mice were fed a low fat (LF) or high fat (HF) diet for 16 weeks (10% and 60% Kcal from fat respectively, Research Diets). In mice implanted with carotid catheter for MAP measurements, subcutaneous (sc) or epididymal white adipose tissue (eWAT) were exposed for saline or capsaicin infusions (0.5 nmol/ul; 4 sites; 4ul/min; 2 min; bilateral; n=4-7). Saline infusion in scWAT or eWAT did not change MAP from baseline in any of the groups. Capsaicin infusion in scWAT decreased MAP response in both C and MSEW HF-fed mice compared to LF (p Diet<0.01), whereas infusion in eWAT increased the MAP response in HF-fed MSEW mice compared to C (7±1 vs. -2.5±3 mmHg; p<0.01). After MAP recordings, fat depots were removed to measure capsaicin-induced CGRP release (1 uM capsaicin). In scWAT, CGRP release was decreased in HF compared to LF similarly in both C and MSEW (p Diet<0.01); however, MSEW increased CGRP release compared to C (p MSEW<0.05). In addition, capsaicin infusion increased the number of Fos positive neurons in the paraventricular nucleus of the hypothalamus in MSEW mice fed a HF diet compared to saline (51±6 vs. 26±4; p<0.05), but not in C. Our results show that male MSEW mice fed a HF may display depot-specific afferent signals that influence acute MAP control. Moreover, the AAR could play an important role in the increased sympathetic tone and blood pressure observed in these mice.