Skip to Content
MilliporeSigma
  • The orphan nuclear receptor Nur77 is a determinant of myofiber size and muscle mass in mice.

The orphan nuclear receptor Nur77 is a determinant of myofiber size and muscle mass in mice.

Molecular and cellular biology (2015-01-22)
Peter Tontonoz, Omar Cortez-Toledo, Kevin Wroblewski, Cynthia Hong, Laura Lim, Rogelio Carranza, Orla Conneely, Daniel Metzger, Lily C Chao
ABSTRACT

We previously showed that the orphan nuclear receptor Nur77 (Nr4a1) plays an important role in the regulation of glucose homeostasis and oxidative metabolism in skeletal muscle. Here, we show using both gain- and loss-of-function models that Nur77 is also a regulator of muscle growth in mice. Transgenic expression of Nur77 in skeletal muscle in mice led to increases in myofiber size. Conversely, mice with global or muscle-specific deficiency in Nur77 exhibited reduced muscle mass and myofiber size. In contrast to Nur77 deficiency, deletion of the highly related nuclear receptor NOR1 (Nr4a3) had minimal effect on muscle mass and myofiber size. We further show that Nur77 mediates its effects on muscle size by orchestrating transcriptional programs that favor muscle growth, including the induction of insulin-like growth factor 1 (IGF1), as well as concomitant downregulation of growth-inhibitory genes, including myostatin, Fbxo32 (MAFbx), and Trim63 (MuRF1). Nur77-mediated increase in IGF1 led to activation of the Akt-mTOR-S6K cascade and the inhibition of FoxO3a activity. The dependence of Nur77 on IGF1 was recapitulated in primary myoblasts, establishing this as a cell-autonomous effect. Collectively, our findings identify Nur77 as a novel regulator of myofiber size and a potential transcriptional link between cellular metabolism and muscle growth.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
R3 IGF-1 human, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
Sigma-Aldrich
Anti-Laminin antibody produced in rabbit, 0.5 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Phenylmethanesulfonyl fluoride, ≥98.5% (GC)
Sigma-Aldrich
ECM Gel from Engelbreth-Holm-Swarm murine sarcoma, liquid, BioReagent, suitable for cell culture
Sigma-Aldrich
Phenylmethanesulfonyl fluoride, ≥99.0% (T)
Sigma-Aldrich
Isopropyl alcohol, ≥99.7%, FCC, FG
Supelco
2-Propanol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
2-Propanol, JIS special grade, ≥99.5%
Sigma-Aldrich
2-Propanol, SAJ first grade, ≥99.0%
Sigma-Aldrich
2-Propanol, suitable for HPLC
Sigma-Aldrich
2-Propanol, anhydrous, 99.5%
Supelco
2-Propanol, analytical standard
Sigma-Aldrich
2-Propanol, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
2-Propanol, 99.5%, HPLC grade
Sigma-Aldrich
2-Propanol, for molecular biology, BioReagent, ≥99.5%
Sigma-Aldrich
2-Propanol, HPLC Plus, for HPLC, GC, and residue analysis, 99.9%, poly coated bottles
Sigma-Aldrich
2-Propanol, ACS reagent, ≥99.5%
USP
2-Propanol, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
2-Propanol, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
Isopropyl alcohol, meets USP testing specifications
Sigma-Aldrich
2-Propanol, ACS reagent, ≥99.5%
Sigma-Aldrich
2-Propanol, Laboratory Reagent, ≥99.5%
Sigma-Aldrich
2-Propanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)
Sigma-Aldrich
2-Propanol, puriss., meets analytical specification of Ph. Eur., BP, USP, ≥99.5% (GC)
Sigma-Aldrich
2-Propanol, ACS reagent, ≥99.5%
Sigma-Aldrich
2-Propanol, puriss. p.a., ACS reagent, ≥99.8% (GC)
Sigma-Aldrich
2-Propanol, suitable for HPLC, 99.5%
Sigma-Aldrich
2-Propanol, suitable for HPLC, 99.9%
Sigma-Aldrich
2-Propanol, HPLC Plus, for HPLC, GC, and residue analysis, 99.9%