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NPJ Aging Mech Dis. 2016 May 12;2:16006. doi: 10.1038/npjamd.2016.6. eCollection 2016.

Cytochrome b5 reductase and the control of lipid metabolism and healthspan.

Author information

1
Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
2
Centro Andaluz de Biología del Desarrollo, and CIBERER, Instituto de Salud Carlos III, Universidad Pablo de Olavide-CSIC, Sevilla, Spain.
3
Departamento de Biología Celular, Fisiología e Inmunología, Facultad de Ciencias, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, Córdoba, Spain.
4
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
5
Magnetic Resonance Imaging and Spectroscopy Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
6
Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL, USA.
7
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
8
Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
9
Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Abstract

Cytochrome b5 reductases (CYB5R) are required for the elongation and desaturation of fatty acids, cholesterol synthesis and mono-oxygenation of cytochrome P450 enzymes, all of which are associated with protection against metabolic disorders. However, the physiological role of CYB5R in the context of metabolism, healthspan and aging remains ill-defined. We generated CYB5R-overexpressing flies (CYB5R-OE) and created a transgenic mouse line overexpressing CYB5R3 (CYB5R3-Tg) in the C57BL/6J background to investigate the function of this class of enzymes as regulators of metabolism and age-associated pathologies. Gender- and/or stage-specific induction of CYB5R, and pharmacological activation of CYB5R with tetrahydroindenoindole extended fly lifespan. Increased expression of CYB5R3 was associated with significant improvements in several metabolic parameters that resulted in modest lifespan extension in mice. Diethylnitrosamine-induced liver carcinogenesis was reduced in CYB5R3-Tg mice. Accumulation of high levels of long-chain polyunsaturated fatty acids, improvement in mitochondrial function, decrease in oxidative damage and inhibition of chronic pro-inflammatory pathways occurred in the transgenic animals. These results indicate that CYB5R represents a new target in the study of genes that regulate lipid metabolism and healthspan.

Conflict of interest statement

The authors declare no conflict of interest.

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