# pRb Function in Mediobasal Hypothalamus in Diet Induced Obesity

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $569,528

## Abstract

Abstract
Obesity is a present and increasing worldwide health threat. The vast majority of obese people contain higher
levels of leptin in the circulation, which can be modeled in wild type mice on high fat diet (HFD) to promote diet
induced obesity (DIO). Positive energy imbalance in the presence of higher leptin levels indicates reductions
in leptin action, which likely contribute to DIO. In this application, we propose to gain better understanding of
leptin action reduction in DIO. Major leptin target neurons that regulate energy balance are localized in
mediobasal hypothalamus (MBH), which is exposed to the circulation due to the incomplete blood-brain barrier
at the Median Eminence. Byproducts in circulation following HFD could therefore impair MBH neuron
homeostasis, which we define as a healthy balance of post-mitotic quiescence, proliferation, survival,
neurogenesis, and differentiation. The tumor suppressor pRb is a central regulator of cellular homeostasis, we
propose to apply the knowledge of pRb function in tumor suppression to study homeostasis of MBH neurons in
DIO. We obtained evidence that HFD induces pRb phosphorylation and inactivation in MBH neurons. We then
tested the effects of expressing an un-phosphorylable pRb (pRbΔP) in MBH to preserve pRb function in DIO,
and found significantly reduced DIO. In this MPI RO1 application, we propose to (1) determine the
mechanisms of pRbΔP function in MBH to inhibit DIO, (2) determine the anti-DIO effects of pRbΔP when
expressed in POMC neurons, (3) identify non-POMC neurons in MBH that contribute to inhibition of DIO when
pRbΔP is expressed in MBH and determine the underlying mechanisms, and (4) determine the translational
potential of our finding that expressing pRbΔP in MBH can inhibit DIO.

## Key facts

- **NIH application ID:** 9977171
- **Project number:** 5R01DK111043-06
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** STREAMSON C CHUA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $569,528
- **Award type:** 5
- **Project period:** 2016-07-10 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977171

## Citation

> US National Institutes of Health, RePORTER application 9977171, pRb Function in Mediobasal Hypothalamus in Diet Induced Obesity (5R01DK111043-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977171. Licensed CC0.

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