Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance
Open accessAbstract
Obesity and type 2 diabetes are associated with mitochondrial dysfunction in adipose tissue, but the role for adipose tissue mitochondria in the development of these disorders is currently unknown. To understand the impact of adipose tissue mitochondria on whole-body metabolism, we have generated a mouse model with disruption of the mitochondrial transcription factor A (TFAM) specifically in fat. F-TFKO adipose tissue exhibit decreased mtDNA copy number, altered levels of proteins of the electron transport chain, and perturbed mitochondrial function with decreased complex I activity and greater oxygen consumption and uncoupling. As a result, F-TFKO mice exhibit higher energy expenditure and are protected from age- and diet-induced obesity, insulin resistance, and hepatosteatosis, despite a greater food intake. Thus, TFAM deletion in the adipose tissue increases mitochondrial oxidation that has positive metabolic effects, suggesting that regulation of adipose tissue mitochondria may be a potential therapeutic target for the treatment of obesity.
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Adipose tissue-specific deletion of TFAM decreased reactive oxygen species, increased mitochondrial fuel oxidation, and protected mice against obesity and insulin resistance.
“adipose tissue–specific deletion of TFAM decreased reactive oxygen species (ROS), increased mitochondrial fuel oxidation, and protected mice against obesity and IR (12).”
From TFAM Enhances Fat Oxidation and Attenuates High-Fat Diet–Induced Insulin Resistance in Skeletal Muscle (2019) · cites this paper as [12]
The Results section reports that ROS levels increased in TFAM-knockdown cell lines, contrary to the claimed decrease. The Discussion also describes increased adipose-tissue oxidative stress in the mice. The paper does support increased mitochondrial oxidation and protection against obesity and insulin resistance; page numbers were not available in our copy. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredEffects of TFAM overexpression in skeletal muscle are distinct from effects reported in other tissues when TFAM is overexpressed or PGC-1α is overexpressed in muscle.
“These effects are distinct from what has been reported in other tissues when TFAM is overexpressed (11,12) or PGC-1α is overexpressed in muscle (38).”
From TFAM Enhances Fat Oxidation and Attenuates High-Fat Diet–Induced Insulin Resistance in Skeletal Muscle (2019) · cites this paper as [12]
The Results describe TFAM deletion in brown and white adipose tissue, not TFAM overexpression in another tissue. The Discussion compares adipose-specific deletion with skeletal-muscle TFAM knockout, but the passages found do not address the effects of TFAM overexpression or establish the claimed contrast. (LLM, conf=0.76)
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References 53 · Cited by 245
- Authors
- Vernochet, C., Mourier, A., Bezy, O., Macotela, Y., Boucher, J., Rardin, M. J., An, D., Lee, K. Y., Ilkayeva, O. R., Zingaretti, C. M., Emanuelli, B., Smyth, G., Cinti, S., Newgard, C. B., Gibson, B. W., Larsson, N.-G., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Max Planck Institute for Biology of Ageing (DE)
- Buck Institute for Research on Aging (US)
- Duke Medical Center (US)
- IRCCS San Raffaele Roma (IT)
- Corresponding author
- Kahn, C. Ronald
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 16
- Issue
- 6
- Pages
- 765-776
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3529641
- OpenAlex
- W2055231034
- Cited by
- 245
- References
- 53
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 11 · 2023: 27 · 2022: 25 · 2021: 22 · 2020: 16 · 2019: 20 · 2018: 15 · 2017: 19 · 2016: 16 · 2015: 17 · 2014: 18 · 2013: 15 · 2012: 1
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK085610, DK-082659, P30-DK36836, R01DK033201, P30DK036836, R01DK082659)
- National Center for Research Resources (S10-RR025545)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- TFAM, obesity, insulin resistance, type 2 diabetes, mitochondrial dysfunction, mitochondrial DNA copy number, electron transport chain, complex I, mitochondrial uncoupling, oxygen consumption, energy expenditure, hepatic steatosis
- MeSH terms
- Animals, Adipose Tissue, Brown, Cell Line, DNA-Binding Proteins, DNA, Mitochondrial, Energy Metabolism, Insulin Resistance, Mitochondria, Obesity, Oxidative Phosphorylation, Oxygen, Transcription Factors, Mice, Knockout, Mitochondrial Proteins, Electron Transport Complex I, Mice, Adipose Tissue, White
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