Divergent skeletal muscle respiratory capacities in rats artificially selected for high and low running ability

A role for Nor1?

Erin J. Stephenson, Nigel K. Stepto, Lauren G. Koch, Steven L. Britton, John A. Hawley

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Inactivity-related diseases are becoming a huge burden on Western society. While there is a major environmental contribution to metabolic health, the intrinsic properties that predispose or protect against particular health traits are harder to define. We used rat models of inborn high running capacity (HCR) and low running capacity (LCR) to determine inherent differences in mitochondrial volume and function, hypothesizing that HCR rats would have greater skeletal muscle respiratory capacity due to an increase in mitochondrial number. Additionally, we sought to determine if there was a link between the expression of the orphan nuclear receptor neuron-derived orphan receptor (Nor)1, a regulator of oxidative metabolism, and inherent skeletal muscle respiratory capacity. LCR rats were 28% heavier (P < 0.0001), and fasting serum insulin concentrations were 62% greater than in HCR rats (P = 0.02). In contrast, HCR rats had better glucose tolerance and reduced adiposity. In the primarily oxidative soleus muscle, maximal respiratory capacity was 21% greater in HCR rats (P = 0.001), for which the relative contribution of fat oxidation was 20% higher than in LCR rats (P = 0.02). This was associated with increased citrate synthase (CS; 33%, P = 0.009) and β-hydroxyacyl-CoA (β-HAD; 33%, P = 0.0003) activities. In the primarily glycolytic extensor digitum longus muscle, CS activity was 29% greater (P = 0.01) and β-HAD activity was 41% (P = 0.0004) greater in HCR rats compared with LCR rats. Mitochondrial DNA copy numbers were also elevated in the extensor digitum longus muscles of HCR rats (35%, P = 0.049) and in soleus muscles (44%, P = 0.16). Additionally, HCR rats had increased protein expression of individual mitochondrial respiratory complexes, CS, and uncoupling protein 3 in both muscle types (all P < 0.05). In both muscles, Nor1 protein was greater in HCR rats compared with LCR rats (P < 0.05). We propose that the differential expression of Nor1 may contribute to the differences in metabolic regulation between LCR and HCR phenotypes.

Original languageEnglish (US)
Pages (from-to)1403-1412
Number of pages10
JournalJournal of Applied Physiology
Volume113
Issue number9
DOIs
StatePublished - Nov 1 2012

Fingerprint

Aptitude
Running
Skeletal Muscle
Muscles
Nuclear Receptor Subfamily 4, Group A, Member 3
Orphan Nuclear Receptors
Mitochondrial Size
Citrate (si)-Synthase
Muscle Proteins
Adiposity
Health
Coenzyme A
Mitochondrial DNA
Fasting

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Divergent skeletal muscle respiratory capacities in rats artificially selected for high and low running ability : A role for Nor1? / Stephenson, Erin J.; Stepto, Nigel K.; Koch, Lauren G.; Britton, Steven L.; Hawley, John A.

In: Journal of Applied Physiology, Vol. 113, No. 9, 01.11.2012, p. 1403-1412.

Research output: Contribution to journalArticle

Stephenson, Erin J. ; Stepto, Nigel K. ; Koch, Lauren G. ; Britton, Steven L. ; Hawley, John A. / Divergent skeletal muscle respiratory capacities in rats artificially selected for high and low running ability : A role for Nor1?. In: Journal of Applied Physiology. 2012 ; Vol. 113, No. 9. pp. 1403-1412.
@article{9ae8a89e1c964cbb9521830c9791993c,
title = "Divergent skeletal muscle respiratory capacities in rats artificially selected for high and low running ability: A role for Nor1?",
abstract = "Inactivity-related diseases are becoming a huge burden on Western society. While there is a major environmental contribution to metabolic health, the intrinsic properties that predispose or protect against particular health traits are harder to define. We used rat models of inborn high running capacity (HCR) and low running capacity (LCR) to determine inherent differences in mitochondrial volume and function, hypothesizing that HCR rats would have greater skeletal muscle respiratory capacity due to an increase in mitochondrial number. Additionally, we sought to determine if there was a link between the expression of the orphan nuclear receptor neuron-derived orphan receptor (Nor)1, a regulator of oxidative metabolism, and inherent skeletal muscle respiratory capacity. LCR rats were 28{\%} heavier (P < 0.0001), and fasting serum insulin concentrations were 62{\%} greater than in HCR rats (P = 0.02). In contrast, HCR rats had better glucose tolerance and reduced adiposity. In the primarily oxidative soleus muscle, maximal respiratory capacity was 21{\%} greater in HCR rats (P = 0.001), for which the relative contribution of fat oxidation was 20{\%} higher than in LCR rats (P = 0.02). This was associated with increased citrate synthase (CS; 33{\%}, P = 0.009) and β-hydroxyacyl-CoA (β-HAD; 33{\%}, P = 0.0003) activities. In the primarily glycolytic extensor digitum longus muscle, CS activity was 29{\%} greater (P = 0.01) and β-HAD activity was 41{\%} (P = 0.0004) greater in HCR rats compared with LCR rats. Mitochondrial DNA copy numbers were also elevated in the extensor digitum longus muscles of HCR rats (35{\%}, P = 0.049) and in soleus muscles (44{\%}, P = 0.16). Additionally, HCR rats had increased protein expression of individual mitochondrial respiratory complexes, CS, and uncoupling protein 3 in both muscle types (all P < 0.05). In both muscles, Nor1 protein was greater in HCR rats compared with LCR rats (P < 0.05). We propose that the differential expression of Nor1 may contribute to the differences in metabolic regulation between LCR and HCR phenotypes.",
author = "Stephenson, {Erin J.} and Stepto, {Nigel K.} and Koch, {Lauren G.} and Britton, {Steven L.} and Hawley, {John A.}",
year = "2012",
month = "11",
day = "1",
doi = "10.1152/japplphysiol.00788.2012",
language = "English (US)",
volume = "113",
pages = "1403--1412",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "9",

}

TY - JOUR

T1 - Divergent skeletal muscle respiratory capacities in rats artificially selected for high and low running ability

T2 - A role for Nor1?

AU - Stephenson, Erin J.

AU - Stepto, Nigel K.

AU - Koch, Lauren G.

AU - Britton, Steven L.

AU - Hawley, John A.

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Inactivity-related diseases are becoming a huge burden on Western society. While there is a major environmental contribution to metabolic health, the intrinsic properties that predispose or protect against particular health traits are harder to define. We used rat models of inborn high running capacity (HCR) and low running capacity (LCR) to determine inherent differences in mitochondrial volume and function, hypothesizing that HCR rats would have greater skeletal muscle respiratory capacity due to an increase in mitochondrial number. Additionally, we sought to determine if there was a link between the expression of the orphan nuclear receptor neuron-derived orphan receptor (Nor)1, a regulator of oxidative metabolism, and inherent skeletal muscle respiratory capacity. LCR rats were 28% heavier (P < 0.0001), and fasting serum insulin concentrations were 62% greater than in HCR rats (P = 0.02). In contrast, HCR rats had better glucose tolerance and reduced adiposity. In the primarily oxidative soleus muscle, maximal respiratory capacity was 21% greater in HCR rats (P = 0.001), for which the relative contribution of fat oxidation was 20% higher than in LCR rats (P = 0.02). This was associated with increased citrate synthase (CS; 33%, P = 0.009) and β-hydroxyacyl-CoA (β-HAD; 33%, P = 0.0003) activities. In the primarily glycolytic extensor digitum longus muscle, CS activity was 29% greater (P = 0.01) and β-HAD activity was 41% (P = 0.0004) greater in HCR rats compared with LCR rats. Mitochondrial DNA copy numbers were also elevated in the extensor digitum longus muscles of HCR rats (35%, P = 0.049) and in soleus muscles (44%, P = 0.16). Additionally, HCR rats had increased protein expression of individual mitochondrial respiratory complexes, CS, and uncoupling protein 3 in both muscle types (all P < 0.05). In both muscles, Nor1 protein was greater in HCR rats compared with LCR rats (P < 0.05). We propose that the differential expression of Nor1 may contribute to the differences in metabolic regulation between LCR and HCR phenotypes.

AB - Inactivity-related diseases are becoming a huge burden on Western society. While there is a major environmental contribution to metabolic health, the intrinsic properties that predispose or protect against particular health traits are harder to define. We used rat models of inborn high running capacity (HCR) and low running capacity (LCR) to determine inherent differences in mitochondrial volume and function, hypothesizing that HCR rats would have greater skeletal muscle respiratory capacity due to an increase in mitochondrial number. Additionally, we sought to determine if there was a link between the expression of the orphan nuclear receptor neuron-derived orphan receptor (Nor)1, a regulator of oxidative metabolism, and inherent skeletal muscle respiratory capacity. LCR rats were 28% heavier (P < 0.0001), and fasting serum insulin concentrations were 62% greater than in HCR rats (P = 0.02). In contrast, HCR rats had better glucose tolerance and reduced adiposity. In the primarily oxidative soleus muscle, maximal respiratory capacity was 21% greater in HCR rats (P = 0.001), for which the relative contribution of fat oxidation was 20% higher than in LCR rats (P = 0.02). This was associated with increased citrate synthase (CS; 33%, P = 0.009) and β-hydroxyacyl-CoA (β-HAD; 33%, P = 0.0003) activities. In the primarily glycolytic extensor digitum longus muscle, CS activity was 29% greater (P = 0.01) and β-HAD activity was 41% (P = 0.0004) greater in HCR rats compared with LCR rats. Mitochondrial DNA copy numbers were also elevated in the extensor digitum longus muscles of HCR rats (35%, P = 0.049) and in soleus muscles (44%, P = 0.16). Additionally, HCR rats had increased protein expression of individual mitochondrial respiratory complexes, CS, and uncoupling protein 3 in both muscle types (all P < 0.05). In both muscles, Nor1 protein was greater in HCR rats compared with LCR rats (P < 0.05). We propose that the differential expression of Nor1 may contribute to the differences in metabolic regulation between LCR and HCR phenotypes.

UR - http://www.scopus.com/inward/record.url?scp=84868321953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868321953&partnerID=8YFLogxK

U2 - 10.1152/japplphysiol.00788.2012

DO - 10.1152/japplphysiol.00788.2012

M3 - Article

VL - 113

SP - 1403

EP - 1412

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 9

ER -