# The role of ventromedial hypothalamic steroidogenic factor-1 neurons in exercise-related metabolism

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2022 · $67,174

## Abstract

PROJECT SUMMARY
Nearly half of the American population is classified as obese and just under one in ten suffer from type 2 diabetes
mellitus (T2DM). Exercise protects against a number of deleterious metabolic changes that correspond with
obesity and T2DM, including impaired glucose metabolism and altered energy balance. The ventromedial
nucleus of the hypothalamus (VMH) is critical for the regulation of whole-body metabolism. Co-sponsor Dr. Joel
Elmquist has shown that the expression of the transcription factor steroidogenic factor-1 (SF1) in the dorsomedial
VMH (VMHdm) is required for normal energy homeostasis in response to metabolic challenges including
exercise. While preliminary work in sponsor Dr. J. Nicholas Betley’s laboratory has shown that the activity of
VMHdm SF1 neurons substantially increases following exercise, it remains unknown how SF1 neural activity
may mediate the metabolic effects of exercise. The main goals of the proposed research are to characterize the
neurophysiology of VMHdm SF1 neurons and their two major subtypes—those that express the leptin and insulin
receptors (LEPR and INSR)—during exercise training; and to determine the role of SF1, LEPR, and INSR neural
activity in exercise-driven changes in energy balance and glucose homeostasis. Specific Aim I experiments will
use fiber photometry and endoscopic calcium imaging to monitor the neural activity of VMHdm SF1, LEPR, and
INSR neurons during and immediately following both acute exercise and chronic exercise training. Specific Aim
II experiments will combine optogenetic manipulation of VMHdm SF1, LEPR, and INSR neurons in in exercising
and sedentary mice with metabolic chamber monitoring and glucose tolerance tests to test the necessity and
sufficiency of these neural populations to drive exercise-related changes in energy balance and glucose
homeostasis. Collectively, these experiments will open avenues for future research into the specific mechanisms
by which VMHdm neural activity contributes to the whole-body homeostatic response to metabolic challenges
such as exercise. The training plan included in this application builds upon the applicant, Dr. Ryan Post’s prior
expertise in systems neuroscience, optogenetics, and fiber photometry as he develops his skills in endoscopic
calcium imaging and metabolic techniques, and enters the field of metabolism. The application’s sponsor, Dr. J.
Nicholas Betley, and co-sponsors, Drs. Joel Elmquist and Junhyong Kim, will be instrumental in Ryan’s
completion of the proposed research and training plan. Given Dr. Betley’s expertise in the contribution of the
central nervous system to metabolism, Dr. Elmquist’s experience as a leader in the field of hypothalamic research
and metabolism, and Dr. Kim’s standing as a pre-eminent cell biologist and successful mentor, they will serve
as invaluable resources to Ryan in his development as an independent scientist. Drs. Betley, Elmquist, and Kim
will also oversee Ryan’s professional develo...

## Key facts

- **NIH application ID:** 10463197
- **Project number:** 1F32DK131892-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ryan James Post
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 1
- **Project period:** 2022-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463197

## Citation

> US National Institutes of Health, RePORTER application 10463197, The role of ventromedial hypothalamic steroidogenic factor-1 neurons in exercise-related metabolism (1F32DK131892-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463197. Licensed CC0.

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