Cited by 234Adipose Tissue and MetabolismMetabolism, Diabetes, and CancerAdipokines, Inflammation, and Metabolic Diseases

Role of adiponectin in human skeletal muscle bioenergetics

Open access
Civitarese, Anthony E., Ukropcova, Barbara, Carling, Stacy, Hulver, Matthew, DeFronzo, Ralph A., Mandarino, Lawrence, Ravussin, Eric, Smith, Steve R.·2006·Cell Metabolism

Abstract

Insulin resistance is associated with impaired skeletal muscle oxidation capacity and reduced mitochondrial number and function. Here, we report that adiponectin signaling regulates mitochondrial bioenergetics in skeletal muscle. Individuals with a family history of type 2 diabetes display skeletal muscle insulin resistance and mitochondrial dysfunction; adiponectin levels strongly correlate with mtDNA content. Knockout of the adiponectin gene in mice is associated with insulin resistance and low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle. Adiponectin treatment of human myotubes in primary culture induces mitochondrial biogenesis, palmitate oxidation, and citrate synthase activity, and reduces the production of reactive oxygen species. The inhibition of adiponectin receptor expression by siRNA, or of AMPK by a pharmacological agent, blunts adiponectin induction of mitochondrial function. Our findings define a skeletal muscle pathway by which adiponectin increases mitochondrial number and function and exerts antidiabetic effects.

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Crossref · 10.1016/j.cmet.2006.05.002

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Authors
Civitarese, A. E., Ukropcova, B., Carling, S., Hulver, M., DeFronzo, R. A., Mandarino, L., Ravussin, E., & Smith, S. R.
Affiliations
  • Pennington Biomedical Research Center (US)
  • The University of Texas at San Antonio Health Science Center (US)
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2006-07
Volume
4
Issue
1
Pages
75-87
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2084362716
Cited by
234
References
82
Citations by year
2026: 8 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 12 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 6 · 2014: 16 · 2013: 19 · 2012: 20
FWCI
11.93
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (U01AG020478, R01 AG20478)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK04796, R56DK024092, DK 24092, R01DK066483, DK066483, P30DK072476, R01DK024092)
  • National Center for Research Resources (M01RR001346)
Topics
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
adiponectin, skeletal muscle, mitochondrial bioenergetics, insulin resistance, type 2 diabetes, mitochondrial biogenesis, mtDNA content, palmitate oxidation, citrate synthase, reactive oxygen species, AMPK, adiponectin receptors, myotubes
MeSH terms
Adult, Animals, Cells, Cultured, Diabetes Mellitus, Type 2, DNA, Mitochondrial, Energy Metabolism, Female, Humans, Insulin Resistance, Male, Mice, Inbred C57BL, Mitochondria, Receptors, Cell Surface, Signal Transduction, Reactive Oxygen Species, Mice, Knockout, Muscle, Skeletal, Muscle Cells, Mice, Adiponectin, Receptors, Adiponectin

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