Imperial College London
Professor Dominic Withers

ProfessorDominicWithers

Faculty of Medicine, Institute of Clinical Sciences

Clinical Chair in Diabetes & Endocrinology
 
 
 
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Contact

 

d.withers

 
 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rached:2019:10.1016/j.molmet.2018.11.010,
author = {Rached, M-T and Millership, SJ and Pedroni, SMA and Choudhury, AI and Costa, ASH and Hardy, DG and Glegola, JA and Irvine, EE and Selman, C and Woodberry, MC and Yadav, VK and Khadayate, S and Vidal-Puig, A and Virtue, S and Frezza, C and Withers, D},
doi = {10.1016/j.molmet.2018.11.010},
journal = {Molecular Metabolism},
pages = {38--50},
title = {Deletion of myeloid IRS2 enhances adipose tissue sympathetic nerve function and limits obesity},
url = {http://dx.doi.org/10.1016/j.molmet.2018.11.010},
volume = {20},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ObjectiveSympathetic nervous system and immune cell interactions play key roles in the regulation of metabolism. For example, recent convergent studies have shown that macrophages regulate obesity through brown adipose tissue (BAT) activation and beiging of white adipose tissue (WAT) via effects upon local catecholamine availability. However, these studies have raised issues about the underlying mechanisms involved including questions regarding the production of catecholamines by macrophages, the role of macrophage polarization state and the underlying intracellular signaling pathways in macrophages that might mediate these effects.MethodsTo address such issues we generated mice lacking Irs2, which mediates the effects of insulin and interleukin 4, specifically in LyzM expressing cells (Irs2LyzM−/− mice).ResultsThese animals displayed obesity resistance and preservation of glucose homeostasis on high fat diet feeding due to increased energy expenditure via enhanced BAT activity and WAT beiging. Macrophages per se did not produce catecholamines but Irs2LyzM−/− mice displayed increased sympathetic nerve density and catecholamine availability in adipose tissue. Irs2-deficient macrophages displayed an anti-inflammatory transcriptional profile and alterations in genes involved in scavenging catecholamines and supporting increased sympathetic innervation.ConclusionsOur studies identify a critical macrophage signaling pathway involved in the regulation of adipose tissue sympathetic nerve function that, in turn, mediates key neuroimmune effects upon systemic metabolism. The insights gained may open therapeutic opportunities for the treatment of obesity.
AU  - Rached,M-T
AU  - Millership,SJ
AU  - Pedroni,SMA
AU  - Choudhury,AI
AU  - Costa,ASH
AU  - Hardy,DG
AU  - Glegola,JA
AU  - Irvine,EE
AU  - Selman,C
AU  - Woodberry,MC
AU  - Yadav,VK
AU  - Khadayate,S
AU  - Vidal-Puig,A
AU  - Virtue,S
AU  - Frezza,C
AU  - Withers,D
DO  - 10.1016/j.molmet.2018.11.010
EP  - 50
PY  - 2019///
SN  - 2212-8778
SP  - 38
TI  - Deletion of myeloid IRS2 enhances adipose tissue sympathetic nerve function and limits obesity
T2  - Molecular Metabolism
UR  - http://dx.doi.org/10.1016/j.molmet.2018.11.010
UR  - http://hdl.handle.net/10044/1/66518
VL  - 20
ER  -
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