# Regulation of Muscle Protein Phenotype in Humans with Obesity

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2022 · $504,829

## Abstract

Project Summary/Abstract
 Distorted expression of isoforms of the skeletal muscle myosin heavy chain (MHC) protein, which collectively
determine the MHC proteome, is a hallmark of altered proteome in muscle of humans with obesity. The most
striking feature of this is a characteristic reduction in the content of the slow MHC-I isoform, which is responsible
for determining the content of Type I muscle fibers. Type I muscle fibers are characterized by increased capacity
for glucose uptake, and in contrast to Type II fibers, maintain their sensitivity to insulin within the adverse
metabolic environment associated with obesity. Increased content of Type I fibers in skeletal muscle, and thus
favorable metabolic effects in muscle, require increased expression of MHC-I in muscle. Importantly, the slow
MHC-I gene drives the molecular mechanisms that determine the overall MHC proteome and fiber type
phenotype in skeletal muscle. We seek to determine the underlying biology that sustains distorted MHC
proteome in skeletal muscle of humans with obesity.
 We will evaluate overall protein turnover in skeletal muscle of humans with obesity and lean controls, and
focus specifically on that of MHC isoforms. We will determine gene expression of the MHC isoforms and
associated molecular factors implicated in activating Type I muscle fiber programing to obtain a deeper insight
into the biology that sustains the unfavorable MHC proteome/muscle fiber phenotype in muscle of humans with
obesity. We will employ acute aerobic exercise and increase in plasma amino acids as experimental tools to
target biological processes of transcription and translation related to MHC genes expression in skeletal muscle.
Ultimately, our findings will provide an understanding of mechanisms responsible for unfavorable MHC proteome
and fiber type phenotype in skeletal muscle of humans with obesity. These findings will advantage our knowledge
about molecular targets that can favorably remodel the muscle proteome and improve metabolism in muscle of
humans with obesity.

## Key facts

- **NIH application ID:** 10439675
- **Project number:** 5R01DK123441-03
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Christos S Katsanos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $504,829
- **Award type:** 5
- **Project period:** 2020-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439675

## Citation

> US National Institutes of Health, RePORTER application 10439675, Regulation of Muscle Protein Phenotype in Humans with Obesity (5R01DK123441-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10439675. Licensed CC0.

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