Chemokine C-C motif ligand 2 overexpression drives tissue-specific metabolic responses in the liver and muscle of mice.

Autor: Luciano-Mateo F; Department of Medicine and Surgery, Universitat Rovira I Virgili, Reus, Spain.; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut D'Investigació Sanitària Pere Virgili, Reus, Spain., Cabré N; Department of Medicine and Surgery, Universitat Rovira I Virgili, Reus, Spain.; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut D'Investigació Sanitària Pere Virgili, Reus, Spain., Fernández-Arroyo S; Department of Medicine and Surgery, Universitat Rovira I Virgili, Reus, Spain.; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut D'Investigació Sanitària Pere Virgili, Reus, Spain., Baiges-Gaya G; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut D'Investigació Sanitària Pere Virgili, Reus, Spain., Hernández-Aguilera A; Department of Medicine and Surgery, Universitat Rovira I Virgili, Reus, Spain.; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut D'Investigació Sanitària Pere Virgili, Reus, Spain., Rodríguez-Tomàs E; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut D'Investigació Sanitària Pere Virgili, Reus, Spain., Muñoz-Pinedo C; Cell Death and Metabolism, Institut D'Investigació Biomèdica de Bellvitge, Barcelona, Spain., Menéndez JA; Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain.; Girona Biomedical Research Institute (IDIBGI), Girona, Spain., Camps J; Department of Medicine and Surgery, Universitat Rovira I Virgili, Reus, Spain. jcamps@grupsagessa.com.; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut D'Investigació Sanitària Pere Virgili, Reus, Spain. jcamps@grupsagessa.com., Joven J; Department of Medicine and Surgery, Universitat Rovira I Virgili, Reus, Spain. jjoven@grupsagessa.com.; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut D'Investigació Sanitària Pere Virgili, Reus, Spain. jjoven@grupsagessa.com.; The Campus of International Excellence Southern Catalonia, Tarragona, Spain. jjoven@grupsagessa.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Jul 20; Vol. 10 (1), pp. 11954. Date of Electronic Publication: 2020 Jul 20.
DOI: 10.1038/s41598-020-68769-7
Abstrakt: Chemokine (C-C motif) ligand 2 (CCL2) has been associated with chronic metabolic diseases. We aimed to investigate whether Ccl2 gene overexpression is involved in the regulation of signaling pathways in metabolic organs. Biochemical and histological analyses were used to explore tissue damage in cisgenic mice that overexpressed the Ccl2 gene. Metabolites from energy and one-carbon metabolism in liver and muscle extracts were measured by targeted metabolomics. Western blot analysis was used to explore the AMP-activated protein kinase (AMPK) and mammalian target of rapamycin pathways. Ccl2 overexpression resulted in steatosis, decreased AMPK activity and altered mitochondrial dynamics in the liver. These changes were associated with decreased oxidative phosphorylation and alterations in the citric acid cycle and transmethylation. In contrast, AMPK activity and its downstream mediators were increased in muscle, where we observed an increase in oxidative phosphorylation and increased concentrations of different metabolites associated with ATP synthesis. In conclusion, Ccl2 overexpression induces distinct metabolic alterations in the liver and muscle that affect mitochondrial dynamics and the regulation of energy sensors involved in cell homeostasis. These data suggest that CCL2 may be a therapeutic target in metabolic diseases.
Databáze: MEDLINE
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