| First Author | Deiuliis JA | Year | 2014 |
| Journal | Obesity (Silver Spring) | Volume | 22 |
| Issue | 5 | Pages | 1264-74 |
| PubMed ID | 24124129 | Mgi Jnum | J:336490 |
| Mgi Id | MGI:6868369 | Doi | 10.1002/oby.20642 |
| Citation | Deiuliis JA, et al. (2014) CXCR3 modulates obesity-induced visceral adipose inflammation and systemic insulin resistance. Obesity (Silver Spring) 22(5):1264-74 |
| abstractText | OBJECTIVE: Chemokine (C-X-C motif) receptor 3 (CXCR3) is a chemokine receptor involved in the regulation of immune cell trafficking and activation. Increased CXCR3 expression in the visceral adipose of obese humans and mice was observed. A pathophysiologic role for CXCR3 in diet-induced obesity (DIO) was hypothesized. METHODS: Wild-type (WT) C57B/L6J and chemokine receptor 3 knockout (CXCR3(-/-) ) mice were fed a high-fat diet (HFD) for 20 weeks followed by assessment of glucose metabolism and visceral adipose tissue (VAT) inflammation. RESULTS: CXCR3(-/-) mice exhibited lower fasting glucose and improved glucose tolerance compared with WT-HFD mice, despite similar body mass. HFD-induced VAT innate and adaptive immune cell infiltration, including immature myeloid cells (CD11b(+) F4/80(lo) Ly6C(+) ), were markedly ameliorated in CXCR3(-/-) mice. In vitro IBIDI and in vivo migration assays demonstrated no CXCR3-mediated effect on macrophage or monocyte migration, respectively. CXCR3(-/-) macrophages, however, had a blunted response to interferon-gamma, a TH 1 cytokine that induces macrophage activation. CONCLUSIONS: A previously unreported role for CXCR3 in the development of HFD-induced insulin resistance (IR) and VAT macrophage infiltration in mice was demonstrated. Our results support pharmaceutical targeting of the CXCR3 receptor as a potential treatment for obesity/IR. |
