Skip to main content

Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization.

Publication ,  Journal Article
Chao, LC; Wroblewski, K; Ilkayeva, OR; Stevens, RD; Bain, J; Meyer, GA; Schenk, S; Martinez, L; Vergnes, L; Narkar, VA; Drew, BG; Hong, C ...
Published in: J Lipid Res
December 2012

Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes. Identifying novel regulators of mitochondrial bioenergetics will broaden our understanding of regulatory checkpoints that coordinate complex metabolic pathways. We previously showed that Nur77, an orphan nuclear receptor of the NR4A family, regulates the expression of genes linked to glucose utilization. Here we demonstrate that expression of Nur77 in skeletal muscle also enhances mitochondrial function. We generated MCK-Nur77 transgenic mice that express wild-type Nur77 specifically in skeletal muscle. Nur77-overexpressing muscle had increased abundance of oxidative muscle fibers and mitochondrial DNA content. Transgenic muscle also exhibited enhanced oxidative metabolism, suggestive of increased mitochondrial activity. Metabolomic analysis confirmed that Nur77 transgenic muscle favored fatty acid oxidation over glucose oxidation, mimicking the metabolic profile of fasting. Nur77 expression also improved the intrinsic respiratory capacity of isolated mitochondria, likely due to the increased abundance of complex I of the electron transport chain. These changes in mitochondrial metabolism translated to improved muscle contractile function ex vivo and improved cold tolerance in vivo. Our studies outline a novel role for Nur77 in the regulation of oxidative metabolism and mitochondrial activity in skeletal muscle.

Duke Scholars

Published In

J Lipid Res

DOI

EISSN

1539-7262

Publication Date

December 2012

Volume

53

Issue

12

Start / End Page

2610 / 2619

Location

United States

Related Subject Headings

  • Promoter Regions, Genetic
  • Oxidation-Reduction
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Muscle, Skeletal
  • Mitochondria, Muscle
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • DNA, Mitochondrial
  • Creatine Kinase
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chao, L. C., Wroblewski, K., Ilkayeva, O. R., Stevens, R. D., Bain, J., Meyer, G. A., … Tontonoz, P. (2012). Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization. J Lipid Res, 53(12), 2610–2619. https://doi.org/10.1194/jlr.M029355
Chao, Lily C., Kevin Wroblewski, Olga R. Ilkayeva, Robert D. Stevens, James Bain, Gretchen A. Meyer, Simon Schenk, et al. “Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization.J Lipid Res 53, no. 12 (December 2012): 2610–19. https://doi.org/10.1194/jlr.M029355.
Chao LC, Wroblewski K, Ilkayeva OR, Stevens RD, Bain J, Meyer GA, et al. Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization. J Lipid Res. 2012 Dec;53(12):2610–9.
Chao, Lily C., et al. “Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization.J Lipid Res, vol. 53, no. 12, Dec. 2012, pp. 2610–19. Pubmed, doi:10.1194/jlr.M029355.
Chao LC, Wroblewski K, Ilkayeva OR, Stevens RD, Bain J, Meyer GA, Schenk S, Martinez L, Vergnes L, Narkar VA, Drew BG, Hong C, Boyadjian R, Hevener AL, Evans RM, Reue K, Spencer MJ, Newgard CB, Tontonoz P. Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization. J Lipid Res. 2012 Dec;53(12):2610–2619.

Published In

J Lipid Res

DOI

EISSN

1539-7262

Publication Date

December 2012

Volume

53

Issue

12

Start / End Page

2610 / 2619

Location

United States

Related Subject Headings

  • Promoter Regions, Genetic
  • Oxidation-Reduction
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Muscle, Skeletal
  • Mitochondria, Muscle
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • DNA, Mitochondrial
  • Creatine Kinase