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IBF-R 调节高脂肪饮食诱导肥胖小鼠中 IRE1α 的翻译后修饰和内质网应激。

IBF-R Regulates IRE1α Post-Translational Modifications and ER Stress in High-Fat Diet-Induced Obese Mice.

机构信息

Department of Pharmacology, Institute of New Drug Development, Medical School, Jeonbuk National University, Jeonju 54896, Jeollabuk-do, Korea.

Non-Clinical Evaluation Center, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Jeollabuk-do, Korea.

出版信息

Nutrients. 2022 Jan 4;14(1):217. doi: 10.3390/nu14010217.

DOI:10.3390/nu14010217
PMID:35011092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8746979/
Abstract

Obesity is a global health issue linked to the heightened risk of several chronic diseases. (RV) is a traditional food supplement used for a range of pharmacological effects such as antitumor, antioxidant, α-glucosidase inhibitory effects, hepatitis, and arthritis. Despite the traditional medicinal values, scientific evidence for its application in obesity is inadequate and unclear. Thus, this investigation was designed to evaluate the anti-obesity effects of IBF-R, an RV extract, using a high-fat diet (HFD) model. The study has six groups: chow diet group; chow diet with 80 mg/kg IBF-R; HFD group; IBF-R group with 20, 40, and 80 mg/kg. IBF-R supplementation significantly regulated the weight gain than the HFD fed mice. Further, IBF-R supplementation lowered the expressions of adipogenic transcription factors such as SREBP-1c, C/EBPα, FAS, and PPAR-γ in white adipose tissue (WAT) of diet-induced obese mice. In addition, IBF-R supplementation reduced the lipogenic gene expression while enhancing genes was related to fatty acid oxidation. Obesity is linked to redox-based post-translational modifications (PTMs) of IRE1α such as S-nitrosylation, endoplasmic reticulum (ER) stress, and chronic metabolic inflammation. The administration of IBF-R inhibits these PTMs. Notably, IBF-R administration significantly enhanced the expression of AMPK and sirtuin 1 in WAT of HFD-fed mice. Together, these findings reveal the IRE1α S-nitrosylation-inflammation axis as a novel mechanism behind the positive implications of IBF-R on obesity. In addition, it lays a firm foundation for the development of extract as a functional ingredient in the food and pharmaceutical industries.

摘要

肥胖是一个全球性的健康问题,与多种慢性疾病的风险增加有关。(RV)是一种传统的食品补充剂,具有多种药理作用,如抗肿瘤、抗氧化、α-葡萄糖苷酶抑制作用、肝炎和关节炎。尽管具有传统的药用价值,但关于其在肥胖中的应用的科学证据不足且不明确。因此,本研究旨在评估 RV 提取物 IBF-R 在高脂肪饮食(HFD)模型中的抗肥胖作用。该研究有六个组:标准饮食组;标准饮食加 80mg/kg IBF-R;HFD 组;IBF-R 组,剂量分别为 20、40 和 80mg/kg。IBF-R 补充剂显著调节了 HFD 喂养小鼠的体重增加。此外,IBF-R 补充剂降低了白色脂肪组织(WAT)中脂肪生成转录因子如 SREBP-1c、C/EBPα、FAS 和 PPAR-γ的表达。此外,IBF-R 补充剂降低了脂肪生成基因的表达,同时增强了与脂肪酸氧化相关的基因。肥胖与 IRE1α 的基于氧化还原的翻译后修饰(PTMs)有关,如 S-亚硝基化、内质网(ER)应激和慢性代谢性炎症。IBF-R 的给药抑制了这些 PTMs。值得注意的是,IBF-R 给药显著增强了 HFD 喂养小鼠 WAT 中 AMPK 和 SIRT1 的表达。总之,这些发现揭示了 IRE1α S-亚硝基化-炎症轴是 IBF-R 对肥胖产生积极影响的新机制。此外,它为将提取物开发为食品和制药行业的功能性成分奠定了坚实的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8746979/cd5f0e978b8e/nutrients-14-00217-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8746979/1dac3d337c33/nutrients-14-00217-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8746979/34dc68dbfe90/nutrients-14-00217-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8746979/06ecfdabf405/nutrients-14-00217-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8746979/cd5f0e978b8e/nutrients-14-00217-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8746979/1dac3d337c33/nutrients-14-00217-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8746979/34dc68dbfe90/nutrients-14-00217-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8746979/06ecfdabf405/nutrients-14-00217-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8746979/cd5f0e978b8e/nutrients-14-00217-g004.jpg

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