Research Paper Volume 10, Issue 10 pp 2657—2667
A high glucose diet induces autophagy in a HLH-30/TFEB-dependent manner and impairs the normal lifespan of C. elegans
- 1 Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
- 2 Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas UNAM - Instituto Nacional de Pediatría, Mexico City 04530, Mexico
- 3 Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
- 4 Consejo Nacional de Ciencia y Tecnología (CONACYT), Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
- 5 Departamento de Química de Biomacromoléculas, Instituto de Química, Universidad Nacional Autónoma de Mexico, Mexico City 04510, Mexico
received: August 7, 2018 ; accepted: September 24, 2018 ; published: October 5, 2018 ;https://doi.org/10.18632/aging.101577
How to Cite
Copyright: Franco-Juárez et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.