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Diabetologia
Published in: Diabetologia 7/2015

01-07-2015 | Article

The receptor CD44 is associated with systemic insulin resistance and proinflammatory macrophages in human adipose tissue

Authors: Li Fen Liu, Keiichi Kodama, Ke Wei, Lorna L. Tolentino, Okmi Choi, Edgar G. Engleman, Atul J. Butte, Tracey McLaughlin

Published in: Diabetologia | Issue 7/2015

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Abstract

Aims/hypothesis

Proinflammatory immune cell infiltration in human adipose tissue is associated with the development of insulin resistance. We previously identified, via a gene expression-based genome-wide association study, the cell-surface immune cell receptor CD44 as a functionally important gene associated with type 2 diabetes. We then showed that, compared with controls, Cd44 knockout mice were protected from insulin resistance and adipose tissue inflammation during diet-induced obesity. We thus sought to test whether CD44 is associated with adipose tissue inflammation and insulin resistance in humans.

Methods

Participants included 58 healthy, overweight/moderately obese white adults who met predetermined criteria for insulin resistance or insulin sensitivity based on the modified insulin-suppression test. Serum was collected from 43 participants to measure circulating concentrations of CD44. Subcutaneous adipose tissue was obtained from 17 participants to compare CD44, its ligand osteopontin (OPN, also known as SPP1) and pro-inflammatory gene expression. CD44 expression on adipose tissue macrophage (ATM) surfaces was determined by flow cytometry.

Results

Serum CD44 concentrations were significantly increased in insulin-resistant (IR) participants. CD44 gene expression in subcutaneous adipose tissue was threefold higher in the IR subgroup. The expression of OPN, CD68 and IL6 was also significantly elevated in IR individuals. CD44 gene expression correlated significantly with CD68 and IL6 expression. CD44 density on ATMs was associated with proinflammatory M1 polarisation.

Conclusions/interpretation

CD44 and OPN in human adipose tissue are associated with localised inflammation and systemic insulin resistance. This receptor–ligand pair is worthy of further research as a potentially modifiable contributor to human insulin resistance and type 2 diabetes.
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Metadata
Title
The receptor CD44 is associated with systemic insulin resistance and proinflammatory macrophages in human adipose tissue
Authors
Li Fen Liu
Keiichi Kodama
Ke Wei
Lorna L. Tolentino
Okmi Choi
Edgar G. Engleman
Atul J. Butte
Tracey McLaughlin
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 7/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3603-y

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