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Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes
Abstract
The tissue-specific role of mitochondrial respiratory capacity in the development of insulin resistance and type 2 diabetes is unclear. We determined mitochondrial function in glycolytic and oxidative skeletal muscle and liver from lean (+/?) and obese diabetic (db/db) mice. In lean mice, the mitochondrial respiration pattern differed between tissues. Tissue-specific mitochondrial profiles were then compared between lean and db/db mice. In liver, mitochondrial respiratory capacity and protein expression, including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), was decreased in db/db mice, consistent with increased mitochondrial fission. In glycolytic muscle, mitochondrial respiration, as well as protein and mRNA expression of mitochondrial markers, was increased in db/db mice, suggesting increased mitochondrial content and fatty acid oxidation capacity. In oxidative muscle, mitochondrial complex I function and PGC-1α and mitochondrial transcription factor A (TFAM) protein levels were decreased in db/db mice, along with increased level of proteins related to mitochondrial dynamics. In conclusion, mitochondrial respiratory performance is under the control of tissue-specific mechanisms and is not uniformly altered in response to obesity. Furthermore, insulin resistance in glycolytic skeletal muscle can be maintained by a mechanism independent of mitochondrial dysfunction. Conversely, insulin resistance in liver and oxidative skeletal muscle from db/db mice is coincident with mitochondrial dysfunction.
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“and with insulin resistance in the same mice model (Holmstrom et al., 2012).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Holmstrom et al., 2012
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Metadata
- Authors
- Holmström, M. H., Iglesias-Gutierrez, E., Zierath, J. R., & Garcia-Roves, P. M.
- Affiliations
- Departments of 1Molecular Medicine and Surgery and
- Physiology and Pharmacology, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden
- Karolinska Institutet (SE)
- Corresponding author
- Zierath, Juleen R.
- ORCID
- Zierath, Juleen R.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2012-03-15
- Volume
- 302
- Issue
- 6
- Pages
- E731-E739
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2112563343
- Cited by
- 137
- References
- 53
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 11 · 2019: 7 · 2018: 13 · 2017: 13 · 2016: 7 · 2015: 11 · 2014: 15 · 2013: 15 · 2012: 6
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mitochondrial respiration, insulin resistance, type 2 diabetes, obesity, db/db mice, skeletal muscle, liver, PGC-1α, TFAM, mitochondrial dynamics, mitochondrial fission, mitochondrial biogenesis, fatty acid oxidation, mitochondrial complex I
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Animal Nutritional Physiological Phenomena, Blood Glucose, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, DNA-Binding Proteins, Glycogen, Glycolysis, High Mobility Group Proteins, Insulin Resistance, Mice, Inbred C57BL, Mice, Obese, Mitochondria, Mitochondria, Liver, Mitochondria, Muscle, Obesity, Oxygen Consumption, Transcription Factors, Triglycerides, Blotting, Western, Trans-Activators, Mice, Inbred NOD, Cell Lineage, Mice, Real-Time Polymerase Chain Reaction
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