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

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $448,038

## Abstract

PROJECT SUMMARY/ABSTRACT
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.
Experimental studies have demonstrated that adipose afferent reflex (AAR) is enhanced in diet-induced
obesity models. Specifically, the acute stimulation of adipose tissue afferent nerve fibers (e.g. capsaicin, leptin)
elevates blood pressure, renal nerve activity and plasma catecholamines. Adipose tissue also expresses
components of the renin-angiotensin system (RAS). Notably, it has been shown that adipose tissue-specific
abrogation of the sole RAS precursor, angiotensinogen (AGT), effectively prevents high fat diet-induced
increases in blood pressure. Our preliminary findings support for the novel central hypothesis postnatal
MSEW aggravates obesity-induced HT in adult life by stimulating AAR reflex-mediated sympathetic
activation and adipose tissue-derived 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. We will assess the effects of MSEW on AAR reflex in acute
and chronic in vivo experiments using a novel state of the art technique, in order to determine the adipose
tissue-brain axis effects on blood pressure; and (2) To test the hypothesis that MSEW exacerbates obesity-
induced hypertension by increasing AGT secretion in adipose tissue. We will generate an adipose tissue-
specific, tamoxifen-inducible AGT knockout mouse, expose the mice to MSEW and wean them on a high fat
diet. The AGT deletion will be induced at three time points from early postnatal life to adulthood, in order to
assess its effects on programming, progression and reversion of hypertension. The outcomes of these studies
may provide novel early life stress-programmed adipose tissue targets with impact on blood pressure control.

## Key facts

- **NIH application ID:** 9838293
- **Project number:** 5R01HL135158-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Analia Loria
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,038
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838293

## Citation

> US National Institutes of Health, RePORTER application 9838293, Effect of early life stress on obesity-induced hypertension in mice (5R01HL135158-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9838293. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*