Inflammation and the IKKβ/IκB/NF-κB axis in obesity- and diet-induced insulin resistance
Abstract
Antidiabetic effects associated with salicylates have been known for years, although the underlying mechanisms were not understood. We have been reinvestigating these effects in the light of recent discoveries in the areas of signal transduction and insulin resistance. Our findings showed that signaling pathways leading to I kappa B kinase beta (IKK beta) and NF-kappa B are activated in insulin-responsive tissues of obese and high-fat-fed animals. Since activation correlates with the development of insulin resistance, we asked whether signaling through this might be involved in the pathogenesis of insulin resistance. Heterozygous gene deletion (Ikk beta+/-) or salicylates, working as IKK beta inhibitors, improved insulin sensitivity in insulin-resistant rodent models. Furthermore, high doses of salicylates (aspirin or salicylate) improved insulin sensitivity in patients with type II diabetes. Our studies implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type II diabetes mellitus and identify the IKK beta/NF-kappa B pathway as a molecular mediator of insulin resistance and pharmacological target for insulin sensitization.
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Inflammatory molecules are likely candidates linking adipose tissue to metabolic, cardiovascular, hepatic and thrombotic complications and certain cancers in obesity.
“Inflammatory molecules are likely candidates exerting a molecular link between the adipose tissue and the metabolic, cardiovascular, hepatic and thrombotic complications, and certain cancer types occurring in conjunction with or as a consequence of human obesity.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [99]
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- Authors
- Shoelson, S. E., Lee, J., & Yuan, M.
- Affiliations
- Joslin Diabetes Center (US)
- Corresponding author
- Shoelson, S E
- ORCID
- Venue
- International Journal of Obesity
- Published
- 2003-11-14
- Volume
- 27
- Issue
- S3
- Pages
- S49-S52
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W1505106993
- Cited by
- 474
- References
- 17
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 10 · 2023: 14 · 2022: 15 · 2021: 19 · 2020: 15 · 2019: 14 · 2018: 20 · 2017: 17 · 2016: 21 · 2015: 17 · 2014: 29 · 2013: 25 · 2012: 25
- FWCI
- 15.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK45943, R01-DK-51729, R01DK045943, R01DK051729)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Keywords
- insulin resistance, obesity, high-fat diet, IKKβ, NF-κB signaling, inflammation, salicylates, aspirin, type 2 diabetes, insulin sensitivity, insulin sensitization
- MeSH terms
- Animals, Dietary Fats, Humans, Inflammation, Insulin Resistance, Obesity, Salicylates, NF-kappa B, Protein Serine-Threonine Kinases, Mice, Rats, I-kappa B Kinase
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