Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals.
Obese adipose tissue is characterized by infiltration of macrophages. We and others recently showed that a specific subset of macrophages is recruited to obese adipose and muscle tissue. This subset expresses CD11c and produces high levels of proinflammatory cytokines that are linked to the development of obesity-associated insulin resistance. Here, we used a conditional cell ablation system, based on transgenic expression of the diphtheria toxin receptor under the control of the CD11c promoter, to study the effects of depletion of CD11c+ cells in obese mouse models. Our results show that CD11c+ cell depletion results in rapid normalization of insulin sensitivity. Furthermore, CD11c+ cell ablation leads to a marked decrease in inflammatory markers, both locally and systemically, as reflected by gene expression and protein levels. Together, these results indicate that these CD11c+ cells are a potential therapeutic target for treatment of obesity-related insulin resistance and type II diabetes.
Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
David
D
Patsouris
Ping-Ping
PP
Li
Divya
D
Thapar
Justin
J
Chapman
Jerrold M
JM
Olefsky
Jaap G
JG
Neels
D000273:Adipose Tissue / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology*; D018932:Chemokine CCL2 / Q000276:immunology; D018925:Chemokines / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000276:immunology*; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000276:immunology*
D039521:CD11c Antigen; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D005947:Glucose