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

<i>Gamma</i>-<i>aminobutyric acid</i> (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...

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Main Authors: Hwa-Young Lee, Geum-Hwa Lee, The-Hiep Hoang, Yu-Mi Kim, Gi-Hyun Jang, Chang-Hwan Seok, Yun-Geum-Sang Gwak, Junghyun Lim, Junghyun Kim, Han-Jung Chae
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Nutrients
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Online Access:https://www.mdpi.com/2072-6643/14/8/1680
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author Hwa-Young Lee
Geum-Hwa Lee
The-Hiep Hoang
Yu-Mi Kim
Gi-Hyun Jang
Chang-Hwan Seok
Yun-Geum-Sang Gwak
Junghyun Lim
Junghyun Kim
Han-Jung Chae
author_facet Hwa-Young Lee
Geum-Hwa Lee
The-Hiep Hoang
Yu-Mi Kim
Gi-Hyun Jang
Chang-Hwan Seok
Yun-Geum-Sang Gwak
Junghyun Lim
Junghyun Kim
Han-Jung Chae
author_sort Hwa-Young Lee
collection DOAJ
description <i>Gamma</i>-<i>aminobutyric acid</i> (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 <i>Curcuma longa</i> 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.
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spelling doaj.art-16db7060769146b9a32f635dc571a7ec2023-11-30T21:41:45ZengMDPI AGNutrients2072-66432022-04-01148168010.3390/nu14081680GABA and Fermented <i>Curcuma longa</i> L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese MiceHwa-Young Lee0Geum-Hwa Lee1The-Hiep Hoang2Yu-Mi Kim3Gi-Hyun Jang4Chang-Hwan Seok5Yun-Geum-Sang Gwak6Junghyun Lim7Junghyun Kim8Han-Jung Chae9Non-Clinical Evaluation Center Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Jeollabuk-do, KoreaNon-Clinical Evaluation Center Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Jeollabuk-do, KoreaNon-Clinical Evaluation Center Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Jeollabuk-do, KoreaBinotec Co., Ltd., 155 Deulan-ro, Suseong-gu, Daegu 41566, Gyeongsangbuk-do, KoreaBinotec Co., Ltd., 155 Deulan-ro, Suseong-gu, Daegu 41566, Gyeongsangbuk-do, KoreaBinotec Co., Ltd., 155 Deulan-ro, Suseong-gu, Daegu 41566, Gyeongsangbuk-do, KoreaBinotec Co., Ltd., 155 Deulan-ro, Suseong-gu, Daegu 41566, Gyeongsangbuk-do, KoreaSchool of Pharmacy, Jeonbuk National University, Jeonju 54896, Jeollabuk-do, KoreaDepartment of Oral Pathology, School of Dentistry, Jeonbuk National University, Jeonju 54896, Jeollabuk-do, KoreaNon-Clinical Evaluation Center Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Jeollabuk-do, Korea<i>Gamma</i>-<i>aminobutyric acid</i> (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 <i>Curcuma longa</i> 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.https://www.mdpi.com/2072-6643/14/8/1680NADPH oxidaseIRE1αSIRT1decayobesity
spellingShingle Hwa-Young Lee
Geum-Hwa Lee
The-Hiep Hoang
Yu-Mi Kim
Gi-Hyun Jang
Chang-Hwan Seok
Yun-Geum-Sang Gwak
Junghyun Lim
Junghyun Kim
Han-Jung Chae
GABA and Fermented <i>Curcuma longa</i> L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice
Nutrients
NADPH oxidase
IRE1α
SIRT1
decay
obesity
title GABA and Fermented <i>Curcuma longa</i> 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 <i>Curcuma longa</i> 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 <i>Curcuma longa</i> 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 <i>Curcuma longa</i> 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 <i>Curcuma longa</i> 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 i curcuma longa i l extract enriched with gaba ameliorate obesity through nox4 ire1α sulfonation ridd sirt1 decay axis in high fat diet induced obese mice
topic NADPH oxidase
IRE1α
SIRT1
decay
obesity
url https://www.mdpi.com/2072-6643/14/8/1680
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