Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2 : A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

Abstract EN

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.