Metabolic effects of CX3CR1 deficiency in diet-induced obese mice

Rachana Shah, Sean M. O'Neill, Christine Hinkle, Jennifer Caughey, Stephen Stephan, Emma Lynch, Kate Bermingham, Gina Lynch, Rexford S Ahima, Muredach P. Reilly

Research output: Contribution to journalArticle

Abstract

The fractalkine (CX3CL1-CX3CR1) chemokine system is associated with obesity-related inflammation and type 2 diabetes, but data on effects of Cx3cr1 deficiency onmetabolic pathways is contradictory. We examined male C57BL/6 Cx3cr1-/- mice on chow and high-fat diet to determine the metabolic effects of Cx3cr1 deficiency.We found no difference in body weight and fat content or feeding and energy expenditure between Cx3cr1-/- and WT mice. Cx3cr1-/- mice had reduced glucose intolerance assessed by intraperitoneal glucose tolerance tests at chow and high-fat fed states, though there was no difference in glucose-stimulated insulin values. Cx3cr1-/- mice also had improved insulin sensitivity at hyperinsulinemiceuglycemic clamp, with higher glucose infusion rate, rate of disposal, and hepatic glucose production suppression compared toWT mice. Enhanced insulin signaling in response to acute intravenous insulin injection was demonstrated in Cx3cr1-/- by increased liver protein levels of phosphorylated AKT and GSK3β proteins. There were no differences in adipose tissue macrophage populations, circulating inflammatory monocytes, adipokines, lipids, or inflammatory markers. In conclusion, we demonstrate amoderate and reproducible protective effect of Cx3cr1 deficiency on glucose intolerance and insulin resistance.

Original languageEnglish (US)
Article numbere0138317
JournalPLoS One
Volume10
Issue number9
DOIs
StatePublished - Sep 22 2015
Externally publishedYes

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Obese Mice
Nutrition
Diet
Glucose
glucose
Chemokine CX3CL1
Insulin
mice
diet
Glucose Intolerance
insulin
insulin resistance
Fats
Insulin Resistance
Adipose Tissue
adipokines
liver protein
Adipokines
Liver
High Fat Diet

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Shah, R., O'Neill, S. M., Hinkle, C., Caughey, J., Stephan, S., Lynch, E., ... Reilly, M. P. (2015). Metabolic effects of CX3CR1 deficiency in diet-induced obese mice. PLoS One, 10(9), [e0138317]. https://doi.org/10.1371/journal.pone.0138317

Metabolic effects of CX3CR1 deficiency in diet-induced obese mice. / Shah, Rachana; O'Neill, Sean M.; Hinkle, Christine; Caughey, Jennifer; Stephan, Stephen; Lynch, Emma; Bermingham, Kate; Lynch, Gina; Ahima, Rexford S; Reilly, Muredach P.

In: PLoS One, Vol. 10, No. 9, e0138317, 22.09.2015.

Research output: Contribution to journalArticle

Shah, R, O'Neill, SM, Hinkle, C, Caughey, J, Stephan, S, Lynch, E, Bermingham, K, Lynch, G, Ahima, RS & Reilly, MP 2015, 'Metabolic effects of CX3CR1 deficiency in diet-induced obese mice', PLoS One, vol. 10, no. 9, e0138317. https://doi.org/10.1371/journal.pone.0138317
Shah R, O'Neill SM, Hinkle C, Caughey J, Stephan S, Lynch E et al. Metabolic effects of CX3CR1 deficiency in diet-induced obese mice. PLoS One. 2015 Sep 22;10(9). e0138317. https://doi.org/10.1371/journal.pone.0138317
Shah, Rachana ; O'Neill, Sean M. ; Hinkle, Christine ; Caughey, Jennifer ; Stephan, Stephen ; Lynch, Emma ; Bermingham, Kate ; Lynch, Gina ; Ahima, Rexford S ; Reilly, Muredach P. / Metabolic effects of CX3CR1 deficiency in diet-induced obese mice. In: PLoS One. 2015 ; Vol. 10, No. 9.
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