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.
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.
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Esther
E
Rodríguez-Gallego
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Marta
M
Riera-Borrull
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Anna
A
Hernández-Aguilera
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Roger
R
Mariné-Casadó
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Anna
A
Rull
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Raúl
R
Beltrán-Debón
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Fedra
F
Luciano-Mateo
Catalan Institute of Oncology and Girona Biomedical Research Institute, Avda de Francia s/n, 17007 Girona, Spain.
Javier A
JA
Menendez
Catalan Institute of Oncology and Girona Biomedical Research Institute, Avda de Francia s/n, 17007 Girona, Spain.
Alejandro
A
Vazquez-Martin
Department of Pathology, Hospital Universitari Joan XXIII, C/ Dr. Mallafrè Guasch 4, 43005 Tarragona, Spain.
Juan J
JJ
Sirvent
Department of Vascular Surgery, Hospital Universitari Joan XXIII, C/ Dr. Mallafrè Guasch 4, 43005 Tarragona, Spain.
Vicente
V
Martín-Paredero
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Angel L
AL
Corbí
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Elena
E
Sierra-Filardi
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Gerard
G
Aragonès
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Anabel
A
García-Heredia
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Jordi
J
Camps
Servei de Medicina Interna, Hospital Sant Pau i Santa Tecla, Rambla Vella 14, 43003 Tarragona, Spain.
Carlos
C
Alonso-Villaverde
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201 Reus, Spain ; Campus of International Excellence Southern Catalonia, Spain.
Jorge
J
Joven
D017667:Adipocytes / Q000473:pathology; D000818:Animals; D001343:Autophagy; D001835:Body Weight; D018932:Chemokine CCL2 / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000235:genetics; D059305:Diet, High-Fat; D002149:Energy Intake; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000209:etiology*; D050356:Lipid Metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D005947:Glucose