CYB5R3 overexpression exhibits sexual dimorphism: Mitochondrial and metabolic adaptations in transgenic female mice during calorie restriction.

Autor: Sánchez-Mendoza LM; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, CeiA3, Córdoba, Spain. Electronic address: bc2samel@uco.es., Pérez-Sánchez C; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, CeiA3, Córdoba, Spain; Rheumatology Service, Reina Sofia Hospital/ Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/University of Cordoba, Cordoba, Spain. Electronic address: b32pesac@uco.es., García-Caballero C; Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, Spain. Electronic address: crisgcomplutense@gmail.com., Pérez-Rodríguez M; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, CeiA3, Córdoba, Spain. Electronic address: b42perom@uco.es., Calero-Rodríguez P; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, CeiA3, Córdoba, Spain. Electronic address: pilar.calero@uco.es., Vellón-García B; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, CeiA3, Córdoba, Spain; Rheumatology Service, Reina Sofia Hospital/ Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/University of Cordoba, Cordoba, Spain. Electronic address: bea.vellon@gmail.com., Moreno JA; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, CeiA3, Córdoba, Spain; Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, Spain. Electronic address: juan.moreno@uco.es., Burón MI; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, CeiA3, Córdoba, Spain. Electronic address: bc1burom@uco.es., de Cabo R; Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA. Electronic address: decabora@grc.nia.nih.gov., González-Reyes JA; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, CeiA3, Córdoba, Spain. Electronic address: bc1gorej@uco.es., Villalba JM; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, CeiA3, Córdoba, Spain. Electronic address: jmvillalba@uco.es.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2024 Oct; Vol. 223, pp. 69-86. Date of Electronic Publication: 2024 Jul 26.
DOI: 10.1016/j.freeradbiomed.2024.07.034
Abstrakt: There is a pressing need to develop new strategies for enhancing health in the elderly and preventing the rise in age-related diseases. Calorie restriction without malnutrition (CR) stands among the different antiaging interventions. Lifelong CR leads to increased expression and activity of plasma membrane CYB5R3, and male mice overexpressing CYB5R3 exhibit some beneficial adaptations that are also seen with CR. However, the mechanisms involved in both interventions could be independent since key aspects of energy metabolism and tissue lipid profile do not coincide, and many of the changes induced by CR in mitochondrial abundance and dynamics in the liver and skeletal muscle could be counteracted by CYB5R3 overexpression. In this study, we sought to elucidate the impact of CR on key markers of metabolic status, mitochondrial function, and pro-oxidant/antioxidant balance in transgenic (TG) female mice overexpressing CYB5R3 compared to their WT littermates. In females fed ad libitum, CYB5R3 overexpression decreased fat mass, led to a preferred utilization of fatty acids as an energy source, upregulated key antioxidant enzymes, and boosted respiration both in skeletal muscle and liver mitochondria, supporting that CYB5R3 overexpression is phenotypic closer to CR in females than in males. Whereas some markers of mitochondrial biogenesis and dynamics were found decreased in TG females on CR, as also found for the levels of Estrogen Receptor α, mitochondrial abundance and activity were maintained both in skeletal muscle and in liver. Our results reveal overlapping metabolic adaptations resulting from the overexpression of CYB5R3 and CR in females, but a specific crosstalk occurs when both interventions are combined, differing from the adaptations observed in TG males.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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