# PE methylation in skeletal muscle energy efficiency

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $36,184

## Abstract

Project Summary/Abstract
A pandemic in obesity-related metabolic diseases has increased at an alarming rate over the last two decades.
Lifestyle changes promote limited success for long-term weight management, while many medical
interventions have side effects. Reduction in energy efficiency might provide an alternative approach to
promote weight loss. As skeletal muscle is an organ with large mass and metabolic demand, energy
inefficiency in skeletal muscle would be predicted to promote substantial increase in whole body energy
expenditure. Studies in membrane vesicles suggest that energy efficiency of sarco/endoplasmic reticulum
(SR/ER) Ca2+-ATPase (SERCA) pump may be modulated by composition of SR phospholipids. In this
application, we propose to investigate the role of phosphatidylethanolamine (PE) methylation in regulating
muscle energy efficiency. PE methylation is catalyzed by an enzyme PE methyltransferase (PEMT), and mice
with whole body deletion of PEMT are protected from diet-induced obesity. We discovered that skeletal
muscles from PEMT knockout mice have elevated metabolic rate, which was likely promoted by a reduction in
SERCA energy efficiency. We hypothesize that PE methylation deficiency reduces SERCA energy efficiency
through its effects on skeletal muscle SR phospholipid composition. Aim 1: With tissue-specific inactivation of
PEMT, we will determine how PE methylation deficiency affects cellular Ca2+ handling to increase skeletal
muscle energy expenditure. Aim 2: In multiple experimental models, we will determine whether alterations in
muscle SR phospholipids would be sufficient to induce changes in resting metabolic rate and propensity for
diet-induced obesity. Aim 3: We will derive mechanical efficiency (η) of contracting muscles with PE
methylation deficiency. We will also examine whether inactivation of PEMT would augment the anti-obesogenic
effect of regular exercise.

## Key facts

- **NIH application ID:** 10242978
- **Project number:** 3R01DK107397-04S1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Katsuhiko Funai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $36,184
- **Award type:** 3
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242978

## Citation

> US National Institutes of Health, RePORTER application 10242978, PE methylation in skeletal muscle energy efficiency (3R01DK107397-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242978. Licensed CC0.

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