Cargando…

GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice

Gamma-aminobutyric acid (GABA) is a natural amino acid with antioxidant activity and is often considered to have therapeutic potential against obesity. Obesity has long been linked to ROS and ER stress, but the effect of GABA on the ROS-associated ER stress axis has not been thoroughly explored. Thu...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Hwa-Young, Lee, Geum-Hwa, Hoang, The-Hiep, Kim, Yu-Mi, Jang, Gi-Hyun, Seok, Chang-Hwan, Gwak, Yun-Geum-Sang, Lim, Junghyun, Kim, Junghyun, Chae, Han-Jung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031358/
https://www.ncbi.nlm.nih.gov/pubmed/35458241
http://dx.doi.org/10.3390/nu14081680
_version_ 1784692370426560512
author Lee, Hwa-Young
Lee, Geum-Hwa
Hoang, The-Hiep
Kim, Yu-Mi
Jang, Gi-Hyun
Seok, Chang-Hwan
Gwak, Yun-Geum-Sang
Lim, Junghyun
Kim, Junghyun
Chae, Han-Jung
author_facet Lee, Hwa-Young
Lee, Geum-Hwa
Hoang, The-Hiep
Kim, Yu-Mi
Jang, Gi-Hyun
Seok, Chang-Hwan
Gwak, Yun-Geum-Sang
Lim, Junghyun
Kim, Junghyun
Chae, Han-Jung
author_sort Lee, Hwa-Young
collection PubMed
description Gamma-aminobutyric acid (GABA) is a natural amino acid with antioxidant activity and is often considered to have therapeutic potential against obesity. Obesity has long been linked to ROS and ER stress, but the effect of GABA on the ROS-associated ER stress axis has not been thoroughly explored. Thus, in this study, the effect of GABA and fermented Curcuma longa L. extract enriched with GABA (FCLL-GABA) on the ROS-related ER stress axis and inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) sulfonation were examined with the HFD model to determine the underlying anti-obesity mechanism. Here, GABA and FCLL-GABA supplementations significantly inhibited the weight gain in HFD fed mice. The GABA and FCLL-GABA supplementation lowered the expressions of adipogenic transcription factors such as PPAR-γ, C/EBPα, FAS, and SREBP-1c in white adipose tissue (WAT) and liver from HFD-fed mice. The enhanced hyper-nutrient dysmetabolism-based NADPH oxidase (Nox) 4 and the resultant IRE1α sulfonation-RIDD-SIRT1 decay under HFD conditions were controlled with GABA and FCLL-GABA. Notably, GABA and FCLL-GABA administration significantly increased AMPK and sirtuin 1 (SIRT1) levels in WAT of HFD-fed mice. These significant observations indicate that ER-localized Nox4-induced IRE1α sulfonation results in the decay of SIRT1 as a novel mechanism behind the positive implications of GABA on obesity. Moreover, the investigation lays a firm foundation for the development of FCLL-GABA as a functional ingredient.
format Online
Article
Text
id pubmed-9031358
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90313582022-04-23 GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice Lee, Hwa-Young Lee, Geum-Hwa Hoang, The-Hiep Kim, Yu-Mi Jang, Gi-Hyun Seok, Chang-Hwan Gwak, Yun-Geum-Sang Lim, Junghyun Kim, Junghyun Chae, Han-Jung Nutrients Article Gamma-aminobutyric acid (GABA) is a natural amino acid with antioxidant activity and is often considered to have therapeutic potential against obesity. Obesity has long been linked to ROS and ER stress, but the effect of GABA on the ROS-associated ER stress axis has not been thoroughly explored. Thus, in this study, the effect of GABA and fermented Curcuma longa L. extract enriched with GABA (FCLL-GABA) on the ROS-related ER stress axis and inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) sulfonation were examined with the HFD model to determine the underlying anti-obesity mechanism. Here, GABA and FCLL-GABA supplementations significantly inhibited the weight gain in HFD fed mice. The GABA and FCLL-GABA supplementation lowered the expressions of adipogenic transcription factors such as PPAR-γ, C/EBPα, FAS, and SREBP-1c in white adipose tissue (WAT) and liver from HFD-fed mice. The enhanced hyper-nutrient dysmetabolism-based NADPH oxidase (Nox) 4 and the resultant IRE1α sulfonation-RIDD-SIRT1 decay under HFD conditions were controlled with GABA and FCLL-GABA. Notably, GABA and FCLL-GABA administration significantly increased AMPK and sirtuin 1 (SIRT1) levels in WAT of HFD-fed mice. These significant observations indicate that ER-localized Nox4-induced IRE1α sulfonation results in the decay of SIRT1 as a novel mechanism behind the positive implications of GABA on obesity. Moreover, the investigation lays a firm foundation for the development of FCLL-GABA as a functional ingredient. MDPI 2022-04-18 /pmc/articles/PMC9031358/ /pubmed/35458241 http://dx.doi.org/10.3390/nu14081680 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Hwa-Young
Lee, Geum-Hwa
Hoang, The-Hiep
Kim, Yu-Mi
Jang, Gi-Hyun
Seok, Chang-Hwan
Gwak, Yun-Geum-Sang
Lim, Junghyun
Kim, Junghyun
Chae, Han-Jung
GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice
title GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice
title_full GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice
title_fullStr GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice
title_full_unstemmed GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice
title_short GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice
title_sort gaba and fermented curcuma longa l. extract enriched with gaba ameliorate obesity through nox4-ire1α sulfonation-ridd-sirt1 decay axis in high-fat diet-induced obese mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031358/
https://www.ncbi.nlm.nih.gov/pubmed/35458241
http://dx.doi.org/10.3390/nu14081680
work_keys_str_mv AT leehwayoung gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice
AT leegeumhwa gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice
AT hoangthehiep gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice
AT kimyumi gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice
AT janggihyun gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice
AT seokchanghwan gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice
AT gwakyungeumsang gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice
AT limjunghyun gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice
AT kimjunghyun gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice
AT chaehanjung gabaandfermentedcurcumalongalextractenrichedwithgabaameliorateobesitythroughnox4ire1asulfonationriddsirt1decayaxisinhighfatdietinducedobesemice