The transcriptional coactivator PGC-1β drives the formation of oxidative type IIX fibers in skeletal muscle.
Open accessAbstract
Skeletal muscle must perform different kinds of work, and distinct fiber types have evolved to accommodate these. Previous work had shown that the transcriptional coactivator PGC-1alpha drives the formation of type I and IIA muscle fibers, which are "slow-twitch" and highly oxidative. We show here that transgenic expression of PGC-1beta, a coactivator functionally similar to but distinct from PGC-1alpha, causes a marked induction of IIX fibers, which are oxidative but have "fast-twitch" biophysical properties. PGC-1beta coactivates the MEF2 family of transcription factors to stimulate the type IIX myosin heavy chain (MHC) promoter. PGC-1beta transgenic muscle fibers are rich in mitochondria and are highly oxidative, at least in part due to coactivation by PGC-1beta of ERRalpha and PPARalpha. Consequently, these transgenic animals can run for longer and at higher work loads than wild-type animals. Together, these data indicate that PGC-1beta drives the formation of highly oxidative fibers containing type IIX MHC.
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Muscle-specific transgenic overexpression of PGC-1β results in increased oxidative fiber content and increased expression of OXPHOS and multiple other mitochondrial genes.
“Muscle-specific transgenic overexpression of PGC-1 results in increased oxidative fiber content and increased expression of OXPHOS and multiple other mitochondrial genes.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [271]
Mice with muscle-specific transgenic overexpression of PGC-1β displayed enhanced endurance and oxidative work.
“Mice displayed enhanced endurance and oxidative work (271).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [271]
PGC-1β has distinct expression profiles in skeletal muscle, being expressed in parallel with myosin IIx rather than type I fibers.
“Although PGC-1-mediated gene expression and function appear to overlap considerably with that of PGC-1␣, PGC-1 has distinct expression profiles in skeletal muscle, being expressed in parallel with myosin IIx rather than type I fibers (271).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [271]
Modest overexpression of PGC-1α and transgenic overexpression of PGC-1β increase oxidative metabolism and insulin sensitivity.
“Taken together, these studies suggest that modest overexpression of PGC-1␣ (261, 262) and transgenic overexpression of PGC-1 (271, 272) increase oxidative metabolism and insulin sensitivity.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [271]
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References 40 · Cited by 370
- Authors
- Arany, Z., Lebrasseur, N., Morris, C., Smith, E., Yang, W., Ma, Y., Chin, S., & Spiegelman, B. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Boston University (US)
- Harvard University (US)
- Corresponding author
- Spiegelman, Bruce M.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 5
- Issue
- 1
- Pages
- 35-46
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2052989289
- Cited by
- 370
- References
- 40
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 14 · 2020: 10 · 2019: 14 · 2018: 11 · 2017: 22 · 2016: 20 · 2015: 19 · 2014: 16 · 2013: 31 · 2012: 40
- FWCI
- 12.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2389 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK54477, DK61562, HL079172)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PGC-1β, PGC-1α, skeletal muscle fiber types, oxidative muscle fibers, MEF2 transcription factors, estrogen-related receptor alpha, PPARα, mitochondrial biogenesis, transgenic mice, endurance running performance, fast-twitch fibers
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Cell Line, Humans, Mice, Transgenic, Mitochondria, Promoter Regions, Genetic, Transcription Factors, Transcriptional Activation, Trans-Activators, Muscle, Skeletal, Muscle Fibers, Fast-Twitch, Myosin Heavy Chains, Mice
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