TY - JOUR
T1 - Metabolic effects of CX3CR1 deficiency in diet-induced obese mice
AU - Shah, Rachana
AU - O'Neill, Sean M.
AU - Hinkle, Christine
AU - Caughey, Jennifer
AU - Stephan, Stephen
AU - Lynch, Emma
AU - Bermingham, Kate
AU - Lynch, Gina
AU - Ahima, Rexford S.
AU - Reilly, Muredach P.
N1 - Publisher Copyright:
© 2015 Shah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/9/22
Y1 - 2015/9/22
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0138317
DO - 10.1371/journal.pone.0138317
M3 - Article
C2 - 26393344
AN - SCOPUS:84947435413
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 9
M1 - e0138317
ER -