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Impaired Mitochondrial Biogenesis in Adipose Tissue in Acquired Obesity
Abstract
Low mitochondrial number and activity have been suggested as underlying factors in obesity, type 2 diabetes, and metabolic syndrome. However, the stage at which mitochondrial dysfunction manifests in adipose tissue after the onset of obesity remains unknown. Here we examined subcutaneous adipose tissue (SAT) samples from healthy monozygotic twin pairs, 22.8–36.2 years of age, who were discordant (ΔBMI >3 kg/m2, mean length of discordance 6.3 ± 0.3 years, n = 26) and concordant (ΔBMI <3 kg/m2, n = 14) for body weight, and assessed their detailed mitochondrial metabolic characteristics: mitochondrial-related transcriptomes with dysregulated pathways, mitochondrial DNA (mtDNA) amount, mtDNA-encoded transcripts, and mitochondrial oxidative phosphorylation (OXPHOS) protein levels. We report global expressional downregulation of mitochondrial oxidative pathways with concomitant downregulation of mtDNA amount, mtDNA-dependent translation system, and protein levels of the OXPHOS machinery in the obese compared with the lean co-twins. Pathway analysis indicated downshifting of fatty acid oxidation, ketone body production and breakdown, and the tricarboxylic acid cycle, which inversely correlated with adiposity, insulin resistance, and inflammatory cytokines. Our results suggest that mitochondrial biogenesis, oxidative metabolic pathways, and OXPHOS proteins in SAT are downregulated in acquired obesity, and are associated with metabolic disturbances already at the preclinical stage.
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“Ultimately, this dysfunction leads to decreased mitochondrial content, decreased genetic material, and decreased rate of OXPHOS [19, 20].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [20]
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BackgroundMitochondrial dynamics in type 2 diabetes: Pathophysiological implications
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“In fact, a downshifting of fatty acid oxidation, ketone body production and breakdown, and tricarboxylic acid cycle was observed and inversely correlated with insulin resistance, adiposity and inflammatory cytokines [42].”
Background
Metadata
- Authors
- Heinonen, S., Buzkova, J., Muniandy, M., Kaksonen, R., Ollikainen, M., Ismail, K., Hakkarainen, A., Lundbom, J., Lundbom, N., Vuolteenaho, K., Moilanen, E., Kaprio, J., Rissanen, A., Suomalainen, A., & Pietiläinen, K. H.
- Affiliations
- University of Helsinki (FI)
- Research Programs Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland
- Tampere University Hospital (FI)
- Corresponding author
- Pietiläinen, Kirsi H.
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2015-05-13
- Volume
- 64
- Issue
- 9
- Pages
- 3135-3145
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2168209245
- Cited by
- 362
- References
- 42
- Citations by year
- 2026: 25 · 2025: 39 · 2024: 39 · 2023: 45 · 2022: 44 · 2021: 38 · 2020: 34 · 2019: 29 · 2018: 20 · 2017: 20 · 2016: 21 · 2015: 8
- FWCI
- 16.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Academy of Finland
- Orion Foundation
- Finnish Foundation for Cardiovascular Research
- European Research Council
- University of Helsinki
- Sigrid Jusélius Foundation
- Novo Nordisk Foundation
- Helsinki University Hospital Research Funds
- Jalmari and Rauha Ahokas Foundation
- Diabetes Research Foundation
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- mitochondrial biogenesis, subcutaneous adipose tissue, monozygotic twin discordance, mitochondrial DNA, oxidative phosphorylation, fatty acid oxidation, ketone body metabolism, TCA cycle, insulin resistance, inflammatory cytokines, mitochondrial transcriptome, type 2 diabetes, metabolic syndrome
- MeSH terms
- Adult, Citric Acid Cycle, DNA, Mitochondrial, Fatty Acids, Female, Gene Expression Regulation, Humans, Inflammation, Insulin Resistance, Ketone Bodies, Male, Mitochondria, Obesity, Oxidative Phosphorylation, Twins, Monozygotic, Case-Control Studies, Cytokines, Gene Expression Profiling, Subcutaneous Fat, Mitochondrial Turnover
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