# Neuronal Mechanisms of Obesity-Induced Hypertension

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2022 · —

## Abstract

Obesity which has become common in the US and among the VA population is a major cause of hypertension,
a principal reversible risk factor for cardiovascular disease. However, the mechanisms underlying the
relationship between obesity and hypertension remain largely unknown. The goal of this proposal is to identify
the neuronal and molecular processes that control sympathetic activity and blood pressure and how
dysregulation in these processes contribute to obesity-associated cardiovascular risks. This proposal is based
on the hypothesis that mTORC1 signaling in the hypothalamic arcuate nucleus neurons are critical for
sympathetic and blood pressure regulation with important pathophysiological implications in obesity. We will
use a multidisciplinary strategy combining unique genetically engineered mouse models that permit selective
modulation of key pathways in defined neurons with novel and cutting edge neuro-technologies to precisely
and remotely modulate the firing of distinct arcuate nucleus neuronal populations in freely moving animals with
sophisticated integrative physiology for sympathetic and cardiovascular phenotyping. We will investigate the
contribution of mTORC1 signaling in arcuate nucleus neurons that express proopiomelanocortin (POMC) or
agouti-related protein (AgRP) to the regulation of sympathetic activity and arterial pressure and obesity-
associated hypertension and sympathetic nerve activation. We will also use chemogenetic and optogenetics to
probe the functional relevance of arcuate nucleus POMC and AgRP neurons for the regulation of arterial
pressure and sympathetic activity in normal and obese states. This work should unravel novel mechanisms
that underlie obesity-associated sympathetic activation and hypertension, making our work of high clinical
relevance. Insights into the cellular and molecular processes that control the sympathetic tone that regulates
cardiovascular function may make it possible to selectively interfere with the damage obesity inflicts on
cardiovascular sympathetic functions.

## Key facts

- **NIH application ID:** 10428499
- **Project number:** 5I01BX004249-04
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** KAMAL RAHMOUNI
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428499

## Citation

> US National Institutes of Health, RePORTER application 10428499, Neuronal Mechanisms of Obesity-Induced Hypertension (5I01BX004249-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10428499. Licensed CC0.

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