TY - JOUR
T1 - Cytochrome b5 reductase and the control of lipid metabolism and healthspan
AU - Martin-Montalvo, Alejandro
AU - Sun, Yaning
AU - Diaz-Ruiz, Alberto
AU - Ali, Ahmed
AU - Gutierrez, Vincent
AU - Palacios, Hector H.
AU - Curtis, Jessica
AU - Siendones, Emilio
AU - Ariza, Julia
AU - Abulwerdi, Gelareh A.
AU - Sun, Xiaoping
AU - Wang, Annie X.
AU - Pearson, Kevin J.
AU - Fishbein, Kenneth W.
AU - Spencer, Richard G.
AU - Wang, Miao
AU - Han, Xianlin
AU - Scheibye-Knudsen, Morten
AU - Baur, Joe A.
AU - Shertzer, Howard G.
AU - Navas, Placido
AU - Villalba, Jose Manuel
AU - Zou, Sige
AU - Bernier, Michel
AU - Cabo, Rafael de
N1 - Publisher Copyright:
© 2016 Japanese Society of Anti-Aging Medicine/Macmillan Publishers Limited.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
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U2 - 10.1038/npjamd.2016.6
DO - 10.1038/npjamd.2016.6
M3 - Article
AN - SCOPUS:85019647801
VL - 2
JO - npj Aging and Mechanisms of Disease
JF - npj Aging and Mechanisms of Disease
IS - 1
M1 - 16006
ER -