# Neuronal Mechanisms of Obesity and Hypertension: Role of the BBSome

> **NIH NIH P01** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $443,446

## Abstract

Abstract:
Obesity which has become common in the United States 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 energy homeostasis and blood pressure and how dysregulation in these
processes contribute to obesity and obesity-associated hypertension. This proposal is based on our recent
work demonstrating the importance of neuronal Bardet Biedl syndrome (BBS) proteins in the regulation of
energy homeostasis and blood pressure. We discovered that the BBSome, a complex of eight BBS proteins, is
required for the trafficking of receptors that underlie neural control of energy homeostasis. We further
hypothesize that defects in the hypothalamic BBSome contribute to common dietary obesity and associated
increase in sympathetic nerve activity and blood pressure. This is supported by our recent intriguing
preliminary data implicating dysfunction of the BBSome in the hypertensive high fat diet-induced obese mice.
To test our hypothesis, we will investigate whether restoring the BBSome in the hypothamus of diet-induced
obese mice alleviate the increased adiposity, energy imbalance, activation of the brain renin-angiotensin
system and the increase in blood pressure and sympathetic nerve activity. We will also determine the cellular
processes underlying the BBSome-mediated trafficking of the receptors regulating energy homeostasis and
use chemogenetics to assess the specificity and extend of the defects caused by disruption of the BBsome in
hypothalamic neurons. These innovative studies which will employ unique and sophisticated genetic strategies,
neuro-techniques and physiologic approaches should unravel novel mechanisms that underlie obesity and
obesity-associated cardiovascular risks, making our work of high clinical relevance. Insights into the cellular
and molecular processes that control energy balance and cardiovascular function may make it possible to
selectively interfere with the damage obesity inflicts on cardiovascular function.

## Key facts

- **NIH application ID:** 10445018
- **Project number:** 5P01HL084207-15
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** KAMAL RAHMOUNI
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $443,446
- **Award type:** 5
- **Project period:** 2007-06-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445018

## Citation

> US National Institutes of Health, RePORTER application 10445018, Neuronal Mechanisms of Obesity and Hypertension: Role of the BBSome (5P01HL084207-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445018. Licensed CC0.

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