β-GPA treatment leads to elevated basal metabolic rate and enhanced hypoxic exercise tolerance in mice.

Trenton T Ross,Jeffrey D Overton,Stephen T Kinsey,Katelyn F Houmard

doi:10.14814/phy2.13192

Trenton T Ross, Jeffrey D Overton + Show 2 more

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https://doi.org/10.14814/phy2.13192

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Journal: Physiological Reports	Publication Date: Mar 1, 2017
Citations: 11	License type: CC BY 4.0

Affiliation: University of North Carolina Wilmington

Abstract

Treatments that increase basal metabolic rate (BMR) and enhance exercise capacity may be useful therapeutic approaches for treating conditions such as type 2 diabetes, obesity, and associated circulatory problems. β‐guanidinopropionic acid (β‐GPA) supplementation decreases high‐energy phosphate concentrations, such as ATP and phosphocreatine (PCr) resulting in an energetic challenge that is similar to both exercise programs and hypoxic conditions. In this study, we administered β‐GPA to mice for 2 or 6 weeks, and investigated the effect on muscle energetic status, body and muscle mass, muscle capillarity, BMR, and normoxic and hypoxic exercise tolerance (NET and HET, respectively). Relative [PCr] and PCr/ATP ratios significantly decreased during both treatment times in the β‐GPA fed mice compared to control mice. Body mass, muscle mass, and muscle fiber size significantly decreased after β‐GPA treatment, whereas muscle capillarity and BMR were significantly increased in β‐GPA fed mice. NET significantly decreased in the 2‐week treatment, but was not significantly different in the 6‐week treatment. HET significantly decreased in 2‐week treatment, but in contrast to NET, significantly increased in the 6‐week‐treated mice compared to control mice. We conclude that β‐GPA induces a cellular energetic response in skeletal muscle similar to that of chronic environmental hypoxia, and this energetic perturbation leads to elevated BMR and increased hypoxic exercise capacity in the absence of hypoxic acclimation.

Highlights

Acute exercise induces an energetic challenge in skeletal muscle by increasing the rate of ATP consumption, which is manifested as a transient reduction in the phosphocreatine (PCr) to ATP ratio during the exercise period, followed by a relatively rapid return to resting levels postexercise (Kushmerick and Conley 2002)
This study demonstrated that both 2- and 6-week b-guanidinopropionic acid (b-GPA) treatments resulted in a lower muscle PCr/ATP ratio, decreased body mass, muscle mass, and fiber size, and increased capillarity and basal metabolic rate (BMR)
Most of these responses are similar to those following hypoxia acclimation, so it is not surprising that mice treated with b-GPA for 6 weeks had an increased exercise tolerance under hypoxic conditions

Summary

Introduction

Acute exercise induces an energetic challenge in skeletal muscle by increasing the rate of ATP consumption, which is manifested as a transient reduction in the phosphocreatine (PCr) to ATP ratio during the exercise period, followed by a relatively rapid return to resting levels postexercise (Kushmerick and Conley 2002). Hypoxia can lead to a reduced PCr/ATP ratio, but unlike exercise, this is not due to an increased rate of ATP consumption. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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