Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals.

Abstract:

: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.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Patsouris D,Li PP,Thapar D,Chapman J,Olefsky JM,Neels JG

doi

10.1016/j.cmet.2008.08.015

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

301-9

issue

4

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(08)00282-9

journal_volume

8

pub_type

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