The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index.
TNF- downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents
Open accessAbstract
Obesity is associated with chronic low-grade inflammation. Thus, at metabolically relevant sites, including adipose tissue and muscle, there is abnormal production of proinflammatory cytokines such as TNF-alpha. Here we demonstrate that eNOS expression was reduced, with a concomitant reduction of mitochondrial biogenesis and function, in white and brown adipose tissue and in the soleus muscle of 3 different animal models of obesity. The genetic deletion of TNF receptor 1 in obese mice restored eNOS expression and mitochondrial biogenesis in fat and muscle; this was associated with less body weight gain than in obese wild-type controls. Furthermore, TNF-alpha downregulated eNOS expression and mitochondrial biogenesis in cultured white and brown adipocytes and muscle satellite cells of mice. The NO donors DETA-NO and SNAP prevented the reduction of mitochondrial biogenesis observed with TNF-alpha. Our findings demonstrate that TNF-alpha impairs mitochondrial biogenesis and function in different tissues of obese rodents by downregulating eNOS expression and suggest a novel pathophysiological process that sustains obesity.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“lower NOS3 abundance is found in both adipose tissue and skeletal muscle of obese humans and rodents [120-124].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [123]
In the citing paper
“was shown to downregulate NOS3 expression and abundance [123, 131-134] by decreasing the stability of NOS3 mRNA [135, 136], effectively shortening its half-life [137].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [123]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
‘Small Changes' to Diet and Physical Activity Behaviors for Weight Management
Hills, A. P., Byrne, N. M., Lindstrom, R. C., & Hill, J. O. (2013) · Obesity Facts · doi:10.1159/000345030 · Cited by 9,526
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Metabolism of Isolated Fat Cells
Rodbell, M. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51687-2 · Cited by 4,647
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L., & Spiegelman, B. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117936 · Cited by 3,543
Kim, H. J., Park, S. Y., Choi, Y. J., Han, S. J., Lee, K. W., & Kim, D. J. (2013) · Hormone Research in Paediatrics · doi:10.1159/000348848 · Cited by 3,061
Cited by
Sorted by citations
Nitric oxide signalling in cardiovascular health and disease
Farah, C., Michel, L. Y. M., & Balligand, J.-L. (2018) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.224 · Cited by 779
Neuroinflammation and psychiatric illness
Najjar, S., Pearlman, D. M., Alper, K., Najjar, A., & Devinsky, O. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-43 · Cited by 733
Transcriptional Control of Mitochondrial Biogenesis and Function
Hock, M. B., & Kralli, A. (2009) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163119 · Cited by 626
PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response
Abu Shelbayeh, O., Arroum, T., Morris, S., & Busch, K. B. (2023) · Antioxidants · doi:10.3390/antiox12051075 · Cited by 552
Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease
Paradies, G. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i39.14205 · Cited by 525
Metadata
- Authors
- Valerio, A.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Valerio, A.
- ORCID
- Valerio, A.
- Venue
- Journal of Clinical Investigation
- Published
- 2006-10-02
- Volume
- 116
- Issue
- 10
- Pages
- 2791-2798
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2147649093
- Cited by
- 327
- References
- 56
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 5 · 2023: 14 · 2022: 10 · 2021: 7 · 2020: 12 · 2019: 14 · 2018: 15 · 2017: 19 · 2016: 14 · 2015: 19 · 2014: 24 · 2013: 16 · 2012: 27
- FWCI
- 14.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Ministero della Salute
- Associazione Italiana per la Ricerca sul Cancro
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- TNF-α, endothelial nitric oxide synthase, mitochondrial biogenesis, obesity, adipose tissue, brown adipose tissue, white adipose tissue, skeletal muscle, TNF receptor 1, low-grade inflammation, nitric oxide, satellite cells, adipocytes, weight gain
- MeSH terms
- Adenosine Triphosphate, Adipose Tissue, Animals, Cells, Cultured, Electron Transport Complex IV, DNA-Binding Proteins, Female, High Mobility Group Proteins, Male, Mice, Inbred C57BL, Mice, Obese, Mitochondria, Obesity, Oxygen Consumption, Rats, Zucker, Tumor Necrosis Factor-alpha, Down-Regulation, Receptors, Tumor Necrosis Factor, Mice, Knockout, Muscle, Skeletal, Nitric Oxide Donors, Cytochromes c, Nuclear Respiratory Factor 1, Mice, Rats, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
