Effect of early life stress on obesity-induced hypertension in mice

提出的摘要/工作范围

Abstract/ scope of work proposed Obesity promotes hypertension, a major risk factor for cardiovascular disease. Epidemiological studies have linked early life stress as a modifiable risk factor for increased body mass index and blood pressure. Using an advantageous mouse model of early life stress that combines postnatal maternal separation and early weaning (MSEW) with a high fat diet, we have identified two potential adipose tissue-derived targets implicated in the pathways by which these mice display exacerbated obesity-induced hypertension. Our preliminary findings support the novel central hypothesis that postnatal MSEW aggravates obesity-induced HT in adult life by stimulating adipose afferent reflex (AAR)-mediated sympathetic activation and adipose tissue-derived angiotensinogen (AGT) secretion. We will test key predictions in two multilevel specific aims: (1) To test the hypothesis that MSEW heightens obesity-induced hypertension by stimulating adipose tissue excitatory signals to increase AAR reflex. In this aim, the applicant will contribute to determine the different neurons that are activated in response to MSEW mice fed a high fat diet and test the afferent reflex in vivo in female mice; and (2) To test the hypothesis that MSEW exacerbates obesity-induced hypertension by increasing AGT secretion in adipose tissue. The applicant will contribute to determine whether changes in circulating angiotensin II influence the activation of the circuventricular organs (CVO).