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Fractalkine and Receptor Linked to Adipose Inflammation

Obese individuals and those with type 2 diabetes have higher levels of fractalkine (CX3CL1)

FRIDAY, May 13 (HealthDay News) -- Fractalkine (CX3CL1) and its receptor CX3CR1 may be involved in adipose inflammation, obesity, insulin resistance, and type 2 diabetes, according to a study published in the May issue of Diabetes.

Rachana Shah, M.D., from the Children's Hospital of Philadelphia, and colleagues assessed the role of CX3CL1 and CX3CR1 in adipose inflammation and type 2 diabetes. They quantified CX3CL1 mRNA and protein from subcutaneous adipose and blood during experimental human toxemia, and in both lean and obese human adipose tissue. They also probed its cellular source, assessed its role in monocyte-adipocyte adhesion using CX3CL1-blocking antibodies, determined the correlation between genetic variations and metabolic traits, and measured plasma CX3CL1 levels in a case-control study of type 2 diabetes.

The investigators found that endotoxemia induced adipose CX3CL1 mRNA and protein (32.7- and 43-fold, respectively,). Compared to lean individuals, obese individuals had significantly higher CX3CL1 levels. Human adipocytes and stromal vascular cells secreted and expressed CX3CL1. Pretreatment with a peroxisome proliferator-activated receptor-γ agonist completely attenuated inflammatory cytokine induction of CX3CL1 in human adipocytes. A putative functional nonsynonymous single nucleotide polymorphism (rs3732378) in the fractalkine receptor was correlated with both adipose and metabolic traits. Individuals with type 2 diabetes had significantly increased levels of CX3CL1 compared to those without diabetes.

"CX3CL1-CX3CR1 is a novel inflammatory adipose chemokine system that modulates monocyte adhesion to adipocytes and is associated with obesity, insulin resistance, and type 2 diabetes. These data provide support for CX3CL1 as a diagnostic and therapeutic target in cardiometabolic disease," the authors write.

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