Ubiquitous transgenic overexpression of C-C Chemokine Ligand 2: A model to Assess the Combined Effect of High Energy Intake and Continous Low-Grade Inflammation

Identifier:  PC:586

Handle: https://hdl.handle.net/20.500.11797/PC586

Authors:  Joven, J.; Alonso-Villaverde, C.; Camps, J.; Garcia-Heredia, A.; Aragones, G.; Sierra-Filardi, E.; Corbi, A.; Martin Paredero, V.; Sirvent, J.; Vazquez-Martin, A.; Menendez, J.; Luciano, F.; Beltran, R.; Rull, A.; Mariné, R.; Hernandez-Aguilera, A.; Riera, M.; Rodriguez-Gallego, E.

Abstract:
Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study.