A high glucose diet induces autophagy in a HLH-30/TFEB-dependent manner and impairs the normal lifespan of C-elegans
Por:
Franco-Juárez B., Mejía-Martínez F., Moreno-Arriola E., Hernández-Vázquez A., Gómez-Manzo S., Marcial-Quino J., Arreguín-Espinosa R., Velázquez-Arellano A., Ortega-Cuellar D.
Publicada:
1 oct 2018
Resumen:
A high-glucose diet (HGD) is associated with the development of
metabolic diseases that decrease life expectancy, including obesity and
type-2 diabetes (T2D); however, the mechanism through which a HGD does
so is still unclear. Autophagy, an evolutionarily conserved mechanism,
has been shown to promote both cell and organismal survival. The goal of
this study was to determine whether exposure of Caenorhabditis elegans
to a HGD affects autophagy and thus contributes to the observed lifespan
reduction under a HGD. Unexpectedly, nematodes exposed to a HGD showed
increased autophagic flux via an HLH-30/TFEB-dependent mechanism because
animals with loss of HLH-30/TFEB, even those with high glucose exposure,
had an extended lifespan, suggesting that HLH-30/TFEB might have
detrimental effects on longevity through autophagy under this stress
condition. Interestingly, pharmacological treatment with okadaic acid,
an inhibitor of the PP2A and PP1 protein phosphatases, blocked HLH-30
nuclear translocation, but not TAX-6/calcineurin suppression by RNAi,
during glucose exposure. Together, our data support the suggested dual
role of HLH-30/TFEB and autophagy, which, depending on the cellular
context, may promote either organismal survival or death.
Filiaciones:
Franco-Juárez B.:
Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas UNAM - Instituto Nacional de Pediatría, Mexico City, 04530, Mexico
Univ Nacl Autonoma Mexico, Inst Nacl Pediat, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04530, DF, Mexico
Mejía-Martínez F.:
Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
Secretaria Salud Mexico, Inst Nacl Pediat, Lab Nutr Expt, Mexico City 04530, DF, Mexico
Moreno-Arriola E.:
Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas UNAM - Instituto Nacional de Pediatría, Mexico City, 04530, Mexico
Univ Nacl Autonoma Mexico, Inst Nacl Pediat, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04530, DF, Mexico
Hernández-Vázquez A.:
Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas UNAM - Instituto Nacional de Pediatría, Mexico City, 04530, Mexico
Univ Nacl Autonoma Mexico, Inst Nacl Pediat, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04530, DF, Mexico
Gómez-Manzo S.:
Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
Secretaria Salud Mexico, Inst Nacl Pediat, Lab Bioquim Genet, Mexico City 04530, DF, Mexico
Marcial-Quino J.:
Consejo Nacional de Ciencia y Tecnología (CONACYT), Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
Secretaria Salud Mexico, Inst Nacl Pediat, Consejo Nacl Ciencia & Tecnol CONACYT, Mexico City 04530, DF, Mexico
Arreguín-Espinosa R.:
Departamento de Química de Biomacromoléculas, Instituto de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Inst Quim, Dept Quim Biomacromol, Mexico City 04510, DF, Mexico
Velázquez-Arellano A.:
Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas UNAM - Instituto Nacional de Pediatría, Mexico City, 04530, Mexico
Univ Nacl Autonoma Mexico, Inst Nacl Pediat, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04530, DF, Mexico
Ortega-Cuellar D.:
Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
Secretaria Salud Mexico, Inst Nacl Pediat, Lab Nutr Expt, Mexico City 04530, DF, Mexico
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