# Mechanisms of metabolic, inflammatory and healthspan enhancement by 17a-estradiol

> **NIH NIH R00** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $248,391

## Abstract

PROJECT SUMMARY/ABSTRACT
The research and career development activities outlined in this application have been designed to equip the
candidate, Dr. Michael Stout, with the scientific and technical expertise necessary to become an independent
investigator. The proposed research aims to elucidate the mechanisms responsible for the alleviation of age-
related metabolic and inflammatory dysfunction by 17α-estradiol and identify the receptor(s)/pathway(s) by
which these effects occur. As such, the candidate will receive additional training in signaling networks directly
relevant to this area of research through intensive coursework and hands-on laboratory experience under the
supervision of Drs. James Kirkland, Eduardo Chini, and Sundeep Khosla. The short-term objectives of this
application are to enhance the candidate's knowledge of nutrient-sensing and inflammatory pathway
interactions and develop technical skills to evaluate these relationships in culture- and animal-model systems.
The long-term goals of this application are to enable the candidate, as a newly-hired faculty member, to secure
protected time for research activities, establish new collaborations, and develop a novel line of research that
produces competitive grant proposals for future funding. Preliminary studies performed by the candidate under
the direction of Dr. James Kirkland indicate that 17α-estradiol enhances metabolic function and alleviates
inflammation in older mice through pathways that are central to metabolic homeostasis and the aging process.
This proposal will expand upon these findings by unraveling the intracellular mechanisms responsible for these
phenotypes while also identifying receptor(s)/pathway(s) by which 17α-estradiol elicits these downstream
effects. The overall hypothesis is that 17α-estradiol signals through an uncharacterized receptor/pathway
leading to activation of AMPK and alleviation of metabolic and inflammatory dysfunction. The candidate will
test this hypothesis through the following aims: 1) Determine if metabolic enhancement by 17α-estradiol is
AMPK-dependent; 2) Determine if 17α-estradiol reduces inflammation by suppressing mTOR and/or NFKB;
and 3) Identify the receptor(s)/pathway(s) by which 17α-estradiol elicits its cellular effects. This work will
significantly enhance the understanding of molecular and cellular pathways by which 17α-estradiol elicits its
effects which could lead to the development of novel treatments for aging- and/or obesity-related metabolic
and inflammatory disorders.

## Key facts

- **NIH application ID:** 9977777
- **Project number:** 5R00AG051661-05
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Michael B Stout
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,391
- **Award type:** 5
- **Project period:** 2018-09-30 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977777

## Citation

> US National Institutes of Health, RePORTER application 9977777, Mechanisms of metabolic, inflammatory and healthspan enhancement by 17a-estradiol (5R00AG051661-05). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/9977777. Licensed CC0.

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