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Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.
Open accessAbstract
Obesity is frequently associated with insulin resistance and abnormal glucose homeostasis. Recent studies in animal models have indicated that TNF-alpha plays an important role in mediating the insulin resistance of obesity through its overexpression in fat tissue. However, the mechanisms linking obesity to insulin resistance and diabetes in humans remain largely unknown. In this study we examined the expression pattern of TNF-alpha mRNA in adipose tissues from 18 control and 19 obese premenopausal women by Northern blot analysis. TNF-alpha protein concentrations in plasma and in conditioned medium of explanted adipose tissue were measured by ELISA. Furthermore, the effects of weight reduction by dietary treatment of obesity on the adipose expression of TNF-alpha mRNA were also analyzed in nine premenopausal obese women, before and after a controlled weight-reduction program. These studies demonstrated that obese individuals express 2.5-fold more TNF-alpha mRNA in fat tissue relative to the lean controls (P < 0.001). Similar increases were also observed in adipose production of TNF-alpha protein but circulating TNF-alpha levels were extremely low or undetectable. A strong positive correlation was observed between TNF-alpha mRNA expression levels in fat tissue and the level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance. Finally, body weight reduction in obese subjects which resulted in improved insulin sensitivity was also associated with a decrease in TNF-alpha mRNA expression (45%, P < 0.001) in fat tissue. These results suggest a role for the abnormal regulation of this cytokine in the pathogenesis of obesity-related insulin resistance.
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“Elevated TNF␣ mRNA and protein levels have also been detected in human obesity (51,52).”
From Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [51]
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Research works printed but not linked: 2
- Hotamisligil, G. S., D. L. Murray, L. N. Choy, and B. M. Spiegelman. 1994. TNF-a inhibits signaling from insulin receptor. Proc. Natl. Acado Sci. USA. 91:4854-4858.
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Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
Adipose Tissue as an Endocrine Organ
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Inflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754
Metadata
- Authors
- Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L., & Spiegelman, B. M.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Spiegelman, B M
- Venue
- Journal of Clinical Investigation
- Published
- 1995-05-01
- Volume
- 95
- Issue
- 5
- Pages
- 2409-2415
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC295872
- OpenAlex
- W1974033843
- Cited by
- 3,543
- References
- 28
- Citations by year
- 2026: 46 · 2025: 67 · 2024: 73 · 2023: 91 · 2022: 100 · 2021: 110 · 2020: 91 · 2019: 130 · 2018: 141 · 2017: 127 · 2016: 123 · 2015: 149 · 2014: 178 · 2013: 183 · 2012: 172
- FWCI
- 41.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5r01dk042539-08, 5r01dk045592-05)
- Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 45592, DK42539)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- TNF-α, obesity, insulin resistance, adipose tissue, TNF-alpha mRNA expression, hyperinsulinemia, weight loss, premenopausal women, adipokines
- MeSH terms
- Adipose Tissue, Adult, Blood Glucose, Cholesterol, Female, Humans, Insulin, Insulin Resistance, Middle Aged, Obesity, Reference Values, Regression Analysis, RNA, Messenger, Thinness, Triglycerides, Tumor Necrosis Factor-alpha, Blotting, Northern, Gene Expression, Body Mass Index, Premenopause
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