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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2022-04-01
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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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language | English |
last_indexed | 2024-03-09T13:11:17Z |
publishDate | 2022-04-01 |
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series | Nutrients |
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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