Journal article
OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance
The EMBO journal, Vol.36(14), pp.2126-2145
07/14/2017
DOI: 10.15252/embj.201696179
PMCID: PMC5510002
PMID: 28607005
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.
Details
- Title: Subtitle
- OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance
- Creators
- Renata Oliveira Pereira - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USASatya M Tadinada - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USAFrederick M Zasadny - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USAKaren Jesus Oliveira - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, USAKarla Maria Pereira Pires - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, USAAngela Olvera - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USAJennifer Jeffers - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USARhonda Souvenir - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USARose Mcglauflin - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USAAlec Seei - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USATrevor Funari - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USAHiromi Sesaki - Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, MD, USAMatthew J Potthoff - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USAChristopher M Adams - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, IA, USAEthan J Anderson - College of Pharmacy, University of Iowa, Iowa City, IA, USAE Dale Abel - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
- Resource Type
- Journal article
- Publication Details
- The EMBO journal, Vol.36(14), pp.2126-2145
- Publisher
- England
- DOI
- 10.15252/embj.201696179
- PMID
- 28607005
- PMCID
- PMC5510002
- ISSN
- 0261-4189
- eISSN
- 1460-2075
- Grant note
- R01 HL127764 / NHLBI NIH HHS R01 HL112413 / NHLBI NIH HHS R01 HL122863 / NHLBI NIH HHS T32 HL007344 / NHLBI NIH HHS R01 HL108379 / NHLBI NIH HHS R01 DK092065 / NIDDK NIH HHS
- Language
- English
- Date published
- 07/14/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984025273602771
Metrics
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