Cited by 327Adipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic DiseasesMuscle Physiology and Disorders

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TNF- downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents

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Valerio, A.·2006·Journal of Clinical Investigation

DOI 10.1172/jci28570

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Abstract

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.

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Authors: Valerio, A.
Affiliations: University of Milan (IT)
Corresponding author: Valerio, A.
ORCID: Valerio, A.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2006-10-02
Volume: 116
Issue: 10
Pages: 2791-2798
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci28570
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

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TNF- downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents

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