# Regulation of Muscle Protein Phenotype in Humans with Obesity

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2021 · $62,031

## Abstract

Project Summary/Abstract
 Obesity is increasing in the developed world, and more than one-third of the adult population (35%) in the
United States are classified as obese. When compared to lean humans, humans with obesity demonstrate
differential expression of proteins in skeletal muscle. Differential expression of skeletal muscle myosin heavy
chain (MHC) protein isoforms, which collectively determine the MHC proteome in skeletal muscle, is a hallmark
of distorted muscle proteome in humans with obesity. The content of the MHC-I isoform is characteristically low,
whereas that of MHC-IIx is high, in skeletal muscle of humans with obesity, resulting in an unfavorable muscle
MHC proteome phenotype that has been consistently linked to obesity-associated adverse metabolic and
functional outcomes. These MHC-specific proteome alterations in muscle of humans with obesity are resistant
to weight-loss interventions, indicating an apparent inflexibility in modifying the MHC proteome in muscle of
humans with obesity, and with life-long physiological and clinical implications.
 We will determine rates of synthesis and breakdown of the overall proteome in skeletal muscle of humans
with obesity and lean controls, along with relevant molecular mechanisms regulating these processes in muscle.
We will focus specifically on the rates of synthesis and breakdown of MHC isoforms, as well as gene expression
of the MHC isoforms. That way, we will be able to obtain a deeper insight on the biology that sustains the
unfavorable MHC proteome phenotype in muscle of humans with obesity. A prerequisite for muscle MHC
proteome remodeling in humans with obesity is an increase in the content of the MHC-I isoform, which is
physiologically achieved by increase in the rate of synthesis of MHC-I. Acute aerobic exercise provides the
muscle with a stimulus to increase MHC-I transcription, while acute increase in plasma amino acids is a powerful
signal to upregulate overall protein translation in muscle. Consequently, by employing acute aerobic exercise
and increase in plasma amino acids as investigational tools to target biological processes of transcription and
translation, respectively, that regulate the rate of synthesis of MHC-I in muscle we expect to understand the
underlying biological mechanisms responsible for distorted MHC proteome in muscle of humans with obesity.
 Overall, these studies will investigate the mechanistic underpinnings responsible for disrupted muscle
proteome homeostasis in skeletal muscle of humans with obesity. Findings from the proposed studies will
provide an understanding particularly of the factors that sustain unfavorable MHC proteome in muscle of humans
with obesity. Furthermore, these findings may provide novel targets for interventions that can favorably remodel
the muscle proteome in obesity to improve metabolism and function in skeletal muscle of humans with obesity.

## Key facts

- **NIH application ID:** 10361952
- **Project number:** 3R01DK123441-02S1
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Christos S Katsanos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $62,031
- **Award type:** 3
- **Project period:** 2020-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10361952

## Citation

> US National Institutes of Health, RePORTER application 10361952, Regulation of Muscle Protein Phenotype in Humans with Obesity (3R01DK123441-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10361952. Licensed CC0.

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