# Skeletal Muscle and Brown Adipose Mechanisms Mediating Cardiovascular Risk Factor Protection in RGS14 KO

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $534,250

## Abstract

Project Summary:
We have generated a mouse knockout (KO) of the regulator of G protein signaling 14 (RGS14). The RGS14 KO
mice live longer than their wild type (WT) littermates and are protected against stress, type 2 diabetes and
obesity, all features related to cardiovascular risk protection. The mechanisms mediating these salutary effects
of the RGS14 KO involve the striated muscle. The RGS14 KO also has increased brown adipose tissue, which
is likely involved in the mechanism of its protective effects. The goal of this proposal is to determine the
mechanisms mediating these salutary actions. We plan to establish the RGS14 KO as a novel model for longevity
and determine to what extent striated muscle specific loss of RGS 14 and brown adipose tissue contribute to
longevity, and protection against obesity and diabetes. In this proposal “diabetes” is used to reflect protection of
glucose utilization and insulin resistance, rather than the clinical disease.
Our long term goal is to develop a clinically useful pharmacological inhibitor of RGS14.
The proposal is based on the following hypotheses:
Hypothesis A: Striated muscle specificity of RGS14 KO protects against the development of insulin resistance,
glucose intolerance and obesity and extends lifespan mediated by increased energy metabolism through
mitochondrial oxidation and protection against oxidative stress through the NAD+/SIRT3/MnSOD pathway.
Hypothesis B: The RGS14 KO has the additional novel feature of increased brown adipose tissue, which also
protects against diabetes, obesity and prolongs lifespan.

## Key facts

- **NIH application ID:** 9900047
- **Project number:** 5R01HL137368-04
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** STEPHEN F VATNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $534,250
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900047

## Citation

> US National Institutes of Health, RePORTER application 9900047, Skeletal Muscle and Brown Adipose Mechanisms Mediating Cardiovascular Risk Factor Protection in RGS14 KO (5R01HL137368-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900047. Licensed CC0.

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