Circulating NOD1 Activators and Hematopoietic NOD1 Contribute to Metabolic Inflammation and Insulin Resistance

Cell Reports

Theresa H. Tam¹  Kenny L. Chan¹  Philip J. Bilan¹  Amira Klip¹  Parastoo Boroumand¹  Zhi Liu¹  Dilshaayee Prabaharan¹  Stephen E. Girardin²  Nichole K. Escalante²  Susan J. Robertson²  David Prescott²  Dana J. Philpott²  Sheila R. Costford³  Michael W. Salter⁴  Noah Fine⁵  Michael Glogauer⁵  YuShan Tu⁶ 

[1] Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada;Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada;Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada;

关键词: inflammation;    insulin resistance;    gut microbiome;    macrophage;    neutrophil;    NOD1;    obesity;   

DOI  :  10.1016/j.celrep.2017.02.027

来源: DOAJ

【 摘 要 】

Insulin resistance is a chronic inflammatory condition accompanying obesity or high fat diets that leads to type 2 diabetes. It is hypothesized that lipids and gut bacterial compounds in particular contribute to metabolic inflammation by activating the immune system; however, the receptors detecting these “instigators” of inflammation remain largely undefined. Here, we show that circulating activators of NOD1, a receptor for bacterial peptidoglycan, increase with high fat feeding in mice, suggesting that NOD1 could be a critical sensor leading to metabolic inflammation. Hematopoietic depletion of NOD1 did not prevent weight gain but protected chimeric mice against diet-induced glucose and insulin intolerance. Mechanistically, while macrophage infiltration of adipose tissue persisted, notably these cells were less pro-inflammatory, had lower CXCL1 production, and consequently, lower neutrophil chemoattraction into the tissue. These findings reveal macrophage NOD1 as a cell-specific target to combat diet-induced inflammation past the step of macrophage infiltration, leading to insulin resistance.

【 授权许可】

Unknown