OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance

Renata Oliveira Pereira, Satya M. Tadinada, Frederick M. Zasadny, Karen Jesus Oliveira, Karla Maria Pereira Pires, Angela Olvera, Jennifer Jeffers, Rhonda Souvenir, Rose Mcglauflin, Alec Seei, Trevor Funari, Hiromi Sesaki, Matthew J. Potthoff, Christopher M. Adams, Ethan J. Anderson, E. Dale Abel

Research output: Contribution to journalArticle

Abstract

Mitochondrial dynamics is a conserved process by which mitochondria undergo repeated cycles of fusion and fission, leading to exchange of mitochondrial genetic content, ions, metabolites, and proteins. Here, we examine the role of the mitochondrial fusion protein optic atrophy 1 (OPA1) in differentiated skeletal muscle by reducing OPA1 gene expression in an inducible manner. OPA1 deficiency in young mice results in non-lethal progressive mitochondrial dysfunction and loss of muscle mass. Mutant mice are resistant to age- and diet-induced weight gain and insulin resistance, by mechanisms that involve activation of ER stress and secretion of fibroblast growth factor 21 (FGF21) from skeletal muscle, resulting in increased metabolic rates and improved whole-body insulin sensitivity. OPA1-elicited mitochondrial dysfunction activates an integrated stress response that locally induces muscle atrophy, but via secretion of FGF21 acts distally to modulate whole-body metabolism.

Original languageEnglish (US)
JournalEMBO Journal
DOIs
StateAccepted/In press - 2017

Fingerprint

Autosomal Dominant Optic Atrophy
Muscle
Insulin Resistance
Optics
Obesity
Insulin
Mitochondrial Dynamics
Muscles
Skeletal Muscle
Fusion reactions
Mitochondria
Muscular Atrophy
Mitochondrial Proteins
Nutrition
Metabolites
Metabolism
Gene expression
Weight Gain
Proteins
Chemical activation

Keywords

  • ER stress
  • FGF21
  • Mitochondrial dysfunction
  • OPA1
  • Skeletal muscle

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pereira, R. O., Tadinada, S. M., Zasadny, F. M., Oliveira, K. J., Pires, K. M. P., Olvera, A., ... Abel, E. D. (Accepted/In press). OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance. EMBO Journal. https://doi.org/10.15252/embj.201696179

OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance. / Pereira, Renata Oliveira; Tadinada, Satya M.; Zasadny, Frederick M.; Oliveira, Karen Jesus; Pires, Karla Maria Pereira; Olvera, Angela; Jeffers, Jennifer; Souvenir, Rhonda; Mcglauflin, Rose; Seei, Alec; Funari, Trevor; Sesaki, Hiromi; Potthoff, Matthew J.; Adams, Christopher M.; Anderson, Ethan J.; Abel, E. Dale.

In: EMBO Journal, 2017.

Research output: Contribution to journalArticle

Pereira, RO, Tadinada, SM, Zasadny, FM, Oliveira, KJ, Pires, KMP, Olvera, A, Jeffers, J, Souvenir, R, Mcglauflin, R, Seei, A, Funari, T, Sesaki, H, Potthoff, MJ, Adams, CM, Anderson, EJ & Abel, ED 2017, 'OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance', EMBO Journal. https://doi.org/10.15252/embj.201696179
Pereira, Renata Oliveira ; Tadinada, Satya M. ; Zasadny, Frederick M. ; Oliveira, Karen Jesus ; Pires, Karla Maria Pereira ; Olvera, Angela ; Jeffers, Jennifer ; Souvenir, Rhonda ; Mcglauflin, Rose ; Seei, Alec ; Funari, Trevor ; Sesaki, Hiromi ; Potthoff, Matthew J. ; Adams, Christopher M. ; Anderson, Ethan J. ; Abel, E. Dale. / OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance. In: EMBO Journal. 2017.
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