Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase

Saswata Talukdar, Dayoung Oh, Gautam Bandyopadhyay, Dongmei Li, Jianfeng Xu, Joanne McNelis, Min Lu, Pingping Li, Qingyun Yan, Yimin Zhu, Jachelle Ofrecio, Michael Lin, Martin B. Brenner, Jerrold M. Olefsky

Research output: Contribution to journalArticle

400 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1407-1412
Number of pages6
JournalNature Medicine
Volume18
Issue number9
DOIs
StatePublished - Sep 1 2012

Fingerprint

Pancreatic Elastase
High Fat Diet
Nutrition
Leukocyte Elastase
Insulin Resistance
Macrophages
Neutrophils
Fats
Insulin
Inflammation
Tissue
Adipose Tissue
Obese Mice
T-cells
Metabolic Diseases
Antigen-Presenting Cells
Medical problems
Eosinophils
Mast Cells
Liver

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Talukdar, S., Oh, D., Bandyopadhyay, G., Li, D., Xu, J., McNelis, J., ... Olefsky, J. M. (2012). Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nature Medicine, 18(9), 1407-1412. https://doi.org/10.1038/nm.2885

Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. / Talukdar, Saswata; Oh, Dayoung; Bandyopadhyay, Gautam; Li, Dongmei; Xu, Jianfeng; McNelis, Joanne; Lu, Min; Li, Pingping; Yan, Qingyun; Zhu, Yimin; Ofrecio, Jachelle; Lin, Michael; Brenner, Martin B.; Olefsky, Jerrold M.

In: Nature Medicine, Vol. 18, No. 9, 01.09.2012, p. 1407-1412.

Research output: Contribution to journalArticle

Talukdar, S, Oh, D, Bandyopadhyay, G, Li, D, Xu, J, McNelis, J, Lu, M, Li, P, Yan, Q, Zhu, Y, Ofrecio, J, Lin, M, Brenner, MB & Olefsky, JM 2012, 'Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase', Nature Medicine, vol. 18, no. 9, pp. 1407-1412. https://doi.org/10.1038/nm.2885
Talukdar, Saswata ; Oh, Dayoung ; Bandyopadhyay, Gautam ; Li, Dongmei ; Xu, Jianfeng ; McNelis, Joanne ; Lu, Min ; Li, Pingping ; Yan, Qingyun ; Zhu, Yimin ; Ofrecio, Jachelle ; Lin, Michael ; Brenner, Martin B. ; Olefsky, Jerrold M. / Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. In: Nature Medicine. 2012 ; Vol. 18, No. 9. pp. 1407-1412.
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