TY - JOUR
T1 - Peritoneal macrophages have an impaired immune response in obesity which can be reversed by subsequent weight loss
AU - Willemsen, Lisa
AU - Neele, Annette E.
AU - van der Velden, Saskia
AU - Prange, Koen H. M.
AU - den Toom, Myrthe
AU - van Roomen, Cindy P. A. A.
AU - Reiche, Myrthe E.
AU - Griffith, Guillermo R.
AU - Gijbels, Marion J. J.
AU - Lutgens, Esther
AU - de Winther, Menno P. J.
PY - 2019
Y1 - 2019
N2 - Introduction Obesity is recognized as a risk factor for various microbial infections. The immune system, which is affected by obesity, plays an important role in the pathophysiology of these infections and other obesity-related comorbidities. Weight loss is considered the most obvious treatment for obesity. However, multiple studies suggest that the comorbidities of obesity may persist after weight loss. Deregulation of immune cells including adipose tissue macrophages of obese individuals has been extensively studied, but how obesity and subsequent weight loss affect immune cell function outside adipose tissue is not well defined. Research design and methods Here we investigated the phenotype of non-adipose tissue macrophages by transcriptional characterization of thioglycollate-elicited peritoneal macrophages (PM) from mice with diet-induced obesity and type 2 diabetes (T2D). Subsequently, we defined the characteristics of PMs after weight loss and mimicked a bacterial infection by exposing PMs to lipopolysaccharide. Results and conclusions In contrast to the proinflammatory phenotype of adipose tissue macrophages in obesity and T2D, we found a deactivated state of PMs in obesity and T2D. Weight loss could reverse this deactivated macrophage phenotype. Anti-inflammatory characteristics of these non-adipose macrophages may explain why patients with obesity and T2D have an impaired immune response against pathogens. Our data also suggest that losing weight restores macrophage function and thus contributes to the reduction of immune-related comorbidities in patients.
AB - Introduction Obesity is recognized as a risk factor for various microbial infections. The immune system, which is affected by obesity, plays an important role in the pathophysiology of these infections and other obesity-related comorbidities. Weight loss is considered the most obvious treatment for obesity. However, multiple studies suggest that the comorbidities of obesity may persist after weight loss. Deregulation of immune cells including adipose tissue macrophages of obese individuals has been extensively studied, but how obesity and subsequent weight loss affect immune cell function outside adipose tissue is not well defined. Research design and methods Here we investigated the phenotype of non-adipose tissue macrophages by transcriptional characterization of thioglycollate-elicited peritoneal macrophages (PM) from mice with diet-induced obesity and type 2 diabetes (T2D). Subsequently, we defined the characteristics of PMs after weight loss and mimicked a bacterial infection by exposing PMs to lipopolysaccharide. Results and conclusions In contrast to the proinflammatory phenotype of adipose tissue macrophages in obesity and T2D, we found a deactivated state of PMs in obesity and T2D. Weight loss could reverse this deactivated macrophage phenotype. Anti-inflammatory characteristics of these non-adipose macrophages may explain why patients with obesity and T2D have an impaired immune response against pathogens. Our data also suggest that losing weight restores macrophage function and thus contributes to the reduction of immune-related comorbidities in patients.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074631885&origin=inward
U2 - https://doi.org/10.1136/bmjdrc-2019-000751
DO - https://doi.org/10.1136/bmjdrc-2019-000751
M3 - Article
C2 - 31798899
SN - 2052-4897
VL - 7
JO - BMJ open diabetes research and care
JF - BMJ open diabetes research and care
IS - 1
M1 - e000751
ER -