The role of chemokine (c-c motif) ligand 2 in inflammation, oxidative stress, aging and metabolism

Identificador:  TDX:2946

Handle: https://hdl.handle.net/20.500.11797/TDX2946

Autors:  Luciano Mateo, Fedra Nicaury

Resum:
Metabolism and immune system are closely interconnected and their interactions play an important role in whole-body homeostasis. The activation, proliferation, differentiation and polarization of the immune cells represent significant metabolic stress, which can compromise the cellular metabolism, homeostasis and energetics requirements. These conditions can promote the chronic metabolic stress and metabolic abnormalities in non-immune pathologies. Nevertheless, how these changes in the immunological profile affect systemic metabolism are still not clear. Growing evidences support that chemokines play a crucial role in all these processes. Specially, the increase of chemokine C-C motif ligand 2 (CCL2) in metabolic diseases suggests the possibility of this chemokine to play a systemic role in the regulation of metabolism. The key question is if increase of CCL2 is the cause or consequence of the problem. For this reason, we explored the effect of CCL2 ablation in the metabolism of mice with a background of hyperlipidemia, hepatic steatosis and metabolic syndrome. In addition, we investigated whether that effect might be conditioned by diet. Obtained results are presented in the first study. These results open a brief to other questions. For example, does CCL2 function go further to its chemoattracting capacity? Can this chemokine affect the systemic energy metabolism? To answer these questions, we generated targeted CCL2 cisgenic mice, which overexpressed CCL2 in all tissues and results are presented in study 2. In study 3 we evaluated the effect of CCL2 overexpression in a mice model of Hutchinson-Gilford progeria syndrome, a model of accelerated aging. The finding of therapeutic targets for the treatment of metabolic diseases is an important point in current investigations in our research group. The conclusions of this thesis suggest that CCL2 could be an important therapeutic target in different metabolic diseases.