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Protection from obesity-induced insulin resistance in mice lacking TNF-α function

Author

Listed:
  • K. Teoman Uysal

    (Harvard School of Public Health)

  • Sarah M. Wiesbrock

    (Harvard School of Public Health)

  • Michael W. Marino

    (Ludwig Institute for Cancer Research, Memorial Sloan Kettering Cancer Center)

  • Gkhan S. Hotamisligil

    (Harvard School of Public Health)

Abstract

Obesity is highly associated with insulin resistance and is the biggest risk factor for non-insulin-dependent diabetes mellitus1,2,3. The molecular basis of this common syndrome, however, is poorly understood. It has been suggested that tumour necrosis factor (TNF)-α is a candidate mediator of insulin resistance in obesity, as it is overexpressed in the adipose tissues of rodents and humans4,5,6,7,8,9,10 and it blocks the action of insulin in cultured cells and whole animals10,11,12,13,14. To investigate the role of TNF-α in obesity and insulin resistance, we have generated obese mice with a targeted null mutation in the gene encoding TNF-α and those encoding the two receptors for TNF-α. The absence of TNF-α resulted in significantly improved insulin sensitivity in both diet-induced obesity and that resulting for the ob/ob model of obesity. The TNFα-deficient obese mice had lower levels of circulating free fatty acids, and were protected from the obesity-related reduction in the insulin receptor signalling in muscle and fat tissues. These results indicate that TNF-α is an important mediator of insulin resistance in obesity through its effects on several important sites of insulin action.

Suggested Citation

  • K. Teoman Uysal & Sarah M. Wiesbrock & Michael W. Marino & Gkhan S. Hotamisligil, 1997. "Protection from obesity-induced insulin resistance in mice lacking TNF-α function," Nature, Nature, vol. 389(6651), pages 610-614, October.
    • Handle: RePEc:nat:nature:v:389:y:1997:i:6651:d:10.1038_39335
    DOI: 10.1038/39335
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    Cited by:

    1. Dong-Keon Lee & Taesam Kim & Junyoung Byeon & Minsik Park & Suji Kim & Joohwan Kim & Seunghwan Choi & Gihwan Lee & Chanin Park & Keun Woo Lee & Yong Jung Kwon & Jeong-Hyung Lee & Young-Guen Kwon & You, 2022. "REDD1 promotes obesity-induced metabolic dysfunction via atypical NF-κB activation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Yeon A. Kim & Joon Beom Park & Min Seok Woo & Sang Yeob Lee & Hye Young Kim & Young Hyun Yoo, 2019. "Persistent Organic Pollutant-Mediated Insulin Resistance," IJERPH, MDPI, vol. 16(3), pages 1-14, February.
    3. Alexander V. Sergeev & David O. Carpenter, 2011. "Increase in Metabolic Syndrome-Related Hospitalizations in Relation to Environmental Sources of Persistent Organic Pollutants," IJERPH, MDPI, vol. 8(3), pages 1-15, March.
    4. Cailan Lindsay Feingold & Abbas Smiley, 2022. "Healthy Sleep Every Day Keeps the Doctor Away," IJERPH, MDPI, vol. 19(17), pages 1-35, August.
    5. Shuai Yan & Anna Santoro & Micah J. Niphakis & Antonio M. Pinto & Christopher L. Jacobs & Rasheed Ahmad & Radu M. Suciu & Bryan R. Fonslow & Rachel A. Herbst-Graham & Nhi Ngo & Cassandra L. Henry & Dy, 2024. "Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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