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β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation

β-Hydroxybutyrate, a ketone body that is used as an energy source in organs such as the brain, muscle, and heart when blood glucose is low, is produced by fatty acid oxidation in the liver under the fasting state. Endoplasmic reticulum (ER) stress is linked with the generation of intracellular react...

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Autores principales: Bae, Ha Ram, Kim, Dae Hyun, Park, Min Hi, Lee, Bonggi, Kim, Min Jo, Lee, Eun Kyeong, Chung, Ki Wung, Kim, Seong Min, Im, Dong Soon, Chung, Hae Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341812/
https://www.ncbi.nlm.nih.gov/pubmed/27661104
http://dx.doi.org/10.18632/oncotarget.12119
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author Bae, Ha Ram
Kim, Dae Hyun
Park, Min Hi
Lee, Bonggi
Kim, Min Jo
Lee, Eun Kyeong
Chung, Ki Wung
Kim, Seong Min
Im, Dong Soon
Chung, Hae Young
author_facet Bae, Ha Ram
Kim, Dae Hyun
Park, Min Hi
Lee, Bonggi
Kim, Min Jo
Lee, Eun Kyeong
Chung, Ki Wung
Kim, Seong Min
Im, Dong Soon
Chung, Hae Young
author_sort Bae, Ha Ram
collection PubMed
description β-Hydroxybutyrate, a ketone body that is used as an energy source in organs such as the brain, muscle, and heart when blood glucose is low, is produced by fatty acid oxidation in the liver under the fasting state. Endoplasmic reticulum (ER) stress is linked with the generation of intracellular reactive oxygen species and the accumulation of misfolded protein in the ER. ER stress is known to induce the NOD-like receptor protein 3 inflammasome, which mediates activation of the proinflammatory cytokine interleukin-1β, whose maturation is caspase-1-dependent. We investigated whether β-hydroxybutyrate modulates ER stress, inflammasome formation, and insulin signaling. Sprague Dawley rats (6 and 24 months of age) that were starved for 3 d and rats treated with β-hydroxybutyrate (200 mg·kg(−1)·d(−1) i.p., for 5 d) were used for in vivo investigations, whereas human hepatoma HepG2 cells were used for in vitro studies. Overexpression of AMPK in cultured cells was performed to elucidate the molecular mechanism. The starvation resulted in increased serum β-hydroxybutyrate levels with decreased ER stress (PERK, IRE1, and ATF6α) and inflammasome (ASC, caspase-1, and NLRP3) formation compared with non-fasted 24-month-old rats. In addition, β-hydroxybutyrate suppressed the increase of ER stress- and inflammasome-related marker proteins. Furthermore, β-hydroxybutyrate treatment increased the expression of manganese superoxide dismutase and catalase via the AMP-activated protein kinase-forkhead box protein O3α transcription factor pathway both in vivo and in vitro. The significance of the current study was the discovery of the potential therapeutic role of β-hydroxybutyrate in suppressing ER-stress-induced inflammasome formation.
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spelling pubmed-53418122017-03-23 β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation Bae, Ha Ram Kim, Dae Hyun Park, Min Hi Lee, Bonggi Kim, Min Jo Lee, Eun Kyeong Chung, Ki Wung Kim, Seong Min Im, Dong Soon Chung, Hae Young Oncotarget Research Paper: Gerotarget (Focus on Aging) β-Hydroxybutyrate, a ketone body that is used as an energy source in organs such as the brain, muscle, and heart when blood glucose is low, is produced by fatty acid oxidation in the liver under the fasting state. Endoplasmic reticulum (ER) stress is linked with the generation of intracellular reactive oxygen species and the accumulation of misfolded protein in the ER. ER stress is known to induce the NOD-like receptor protein 3 inflammasome, which mediates activation of the proinflammatory cytokine interleukin-1β, whose maturation is caspase-1-dependent. We investigated whether β-hydroxybutyrate modulates ER stress, inflammasome formation, and insulin signaling. Sprague Dawley rats (6 and 24 months of age) that were starved for 3 d and rats treated with β-hydroxybutyrate (200 mg·kg(−1)·d(−1) i.p., for 5 d) were used for in vivo investigations, whereas human hepatoma HepG2 cells were used for in vitro studies. Overexpression of AMPK in cultured cells was performed to elucidate the molecular mechanism. The starvation resulted in increased serum β-hydroxybutyrate levels with decreased ER stress (PERK, IRE1, and ATF6α) and inflammasome (ASC, caspase-1, and NLRP3) formation compared with non-fasted 24-month-old rats. In addition, β-hydroxybutyrate suppressed the increase of ER stress- and inflammasome-related marker proteins. Furthermore, β-hydroxybutyrate treatment increased the expression of manganese superoxide dismutase and catalase via the AMP-activated protein kinase-forkhead box protein O3α transcription factor pathway both in vivo and in vitro. The significance of the current study was the discovery of the potential therapeutic role of β-hydroxybutyrate in suppressing ER-stress-induced inflammasome formation. Impact Journals LLC 2016-09-19 /pmc/articles/PMC5341812/ /pubmed/27661104 http://dx.doi.org/10.18632/oncotarget.12119 Text en Copyright: © 2016 Bae et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Gerotarget (Focus on Aging)
Bae, Ha Ram
Kim, Dae Hyun
Park, Min Hi
Lee, Bonggi
Kim, Min Jo
Lee, Eun Kyeong
Chung, Ki Wung
Kim, Seong Min
Im, Dong Soon
Chung, Hae Young
β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation
title β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation
title_full β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation
title_fullStr β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation
title_full_unstemmed β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation
title_short β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation
title_sort β-hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via ampk activation
topic Research Paper: Gerotarget (Focus on Aging)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341812/
https://www.ncbi.nlm.nih.gov/pubmed/27661104
http://dx.doi.org/10.18632/oncotarget.12119
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