The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase
Open accessAbstract
Chronic low-grade adipose tissue and liver inflammation is a major cause of systemic insulin resistance and is a key component of the low degree of insulin sensitivity that exists in obesity and type 2 diabetes. Immune cells, such as macrophages, T cells, B cells, mast cells and eosinophils, have all been implicated as having a role in this process. Neutrophils are typically the first immune cells to respond to inflammation and can exacerbate the chronic inflammatory state by helping to recruit macrophages and by interacting with antigen-presenting cells. Neutrophils secrete several proteases, one of which is neutrophil elastase, which can promote inflammatory responses in several disease models. Here we show that treatment of hepatocytes with neutrophil elastase causes cellular insulin resistance and that deletion of neutrophil elastase in high-fat-diet–induced obese (DIO) mice leads to less tissue inflammation that is associated with lower adipose tissue neutrophil and macrophage content. These changes are accompanied by improved glucose tolerance and increased insulin sensitivity. Taken together, we show that neutrophils can be added to the extensive repertoire of immune cells that participate in inflammation-induced metabolic disease.
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Cites
Inflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769
Inflammatory Mechanisms in Obesity
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Neutrophils and immunity: challenges and opportunities
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Self-citationNishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M., Otsu, M., Hara, K., Ueki, K., Sugiura, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.1964 · Cited by 2,230
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Normalization of obesity-associated insulin resistance through immunotherapy
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Increased Hepatic Myeloperoxidase Activity in Obese Subjects with Nonalcoholic Steatohepatitis
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Cited by
Neutrophil recruitment and function in health and inflammation
Kolaczkowska, E., & Kubes, P. (2013) · Nature Reviews Immunology · doi:10.1038/nri3399 · Cited by 5,472
Neutrophil extracellular traps in immunity and disease
Papayannopoulos, V. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.105 · Cited by 3,397
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
Self-citationAdipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947
Metadata
- Authors
- Talukdar, S., Oh, D. Y., Bandyopadhyay, G., Li, D., Xu, J., McNelis, J., Lu, M., Li, P., Yan, Q., Zhu, Y., Ofrecio, J., Lin, M., Brenner, M. B., & Olefsky, J. M.
- Venue
- Nature Medicine
- Published
- 2012-08-05
- Volume
- 18
- Issue
- 9
- Pages
- 1407-1412
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2053142936
- Cited by
- 960
- References
- 9
- FWCI
- 46.96
- Type
- journal article
- Language
- en
- Open access
- green
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- Talukdar, S., Oh, D. Y., Bandyopadhyay, G., Li, D., Xu, J., McNelis, J., Lu, M., Li, P., Yan, Q., Zhu, Y., Ofrecio, J., Lin, M., Brenner, M. B., & Olefsky, J. M. (2012). Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nature Medicine. https://doi.org/10.1038/nm.2885
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