, a bio/informatics shared resource is still "open for business" - Visit the CDS website

Loss of CCR5 results in glucose intolerance in diet-induced obese mice.

Kennedy A, Webb CD, Hill AA, Gruen ML, Jackson LG, Hasty AH
Am J Physiol Endocrinol Metab. 2013 305 (7): E897-906

PMID: 23941876 · PMCID: PMC3798705 · DOI:10.1152/ajpendo.00177.2013

Macrophage and T cell infiltration into metabolic tissues contributes to obesity-associated inflammation and insulin resistance (IR). C-C chemokine receptor 5 (CCR5), expressed on macrophages and T cells, plays a critical role in the recruitment and activation of proinflammatory M1 and TH1 immune cells to tissues and is elevated in adipose tissue (AT) and liver of obese humans and mice. Thus, we hypothesized that deficiency of CCR5 would protect against diet-induced inflammation and IR. CCR5-deficient (CCR5(-/-)) mice and C57BL/6 (WT) controls were fed 10% low-fat (LF) or 60% high-fat (HF) diets for 16 wk. HF feeding increased adiposity, blood glucose, and plasma insulin levels equally in both genotypes. Opposing our hypothesis, HF-fed CCR5(-/-) mice were significantly more glucose intolerant than WT mice. In AT, there was a significant reduction in the M1-associated gene CD11c, whereas M2 associated genes were not different between genotypes. In addition, HF feeding caused a twofold increase in CD4(+) T cells in the AT of CCR5(-/-) compared with WT mice. In liver and muscle, no differences in immune cell infiltration or inflammatory cytokine expression were detected. However, in AT and muscle, there was a mild reduction in insulin-induced phosphorylation of AKT and IRĪ² in CCR5(-/-) compared with WT mice. These findings suggest that whereas CCR5 plays a minor role in regulating immune cell infiltration and inflammation in metabolic tissues, deficiency of CCR5 impairs systemic glucose tolerance as well as AT and muscle insulin signaling.

MeSH Terms (13)

Adipose Tissue Animals Glucose Glucose Intolerance Inflammation Insulin Insulin Resistance Macrophages Mice Mice, Knockout Mice, Obese Muscle, Skeletal Receptors, CCR5

Connections (4)

This publication is referenced by other Labnodes entities: