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展青霉素通过调节线粒体呼吸改善肥大性脂质积累和脂多糖诱导的炎症反应。

Patulin Ameliorates Hypertrophied Lipid Accumulation and Lipopolysaccharide-Induced Inflammatory Response by Modulating Mitochondrial Respiration.

作者信息

Hong Seulmin, Park Seon Kyeong, Lee Jangho, Park Soo Hyun, Kim Young-Soo, Park Jae-Ho, Yu Seungmin, Lee Yu Geon

机构信息

Personalized Diet Research Group, Korea Food Research Institute (KFRI), Wanju 55365, Republic of Korea.

Department of Food Science & Technology, Jeonbuk National University, Jeonju 54896, Republic of Korea.

出版信息

Antioxidants (Basel). 2023 Sep 11;12(9):1750. doi: 10.3390/antiox12091750.

DOI:10.3390/antiox12091750
PMID:37760053
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10526082/
Abstract

Patulin (PAT) is a natural mycotoxin found in decaying pome fruits. Although some toxicological studies have been conducted on PAT, recent research has highlighted its anticancer and antifungal effects. However, studies have yet to examine the effects and molecular mechanisms of PAT in other metabolic diseases. Obesity is a chronic disease caused by excessive food intake and abnormal lifestyle, leading to low-grade inflammation. Therefore, this study aimed to elucidate the effect of PAT on obesity at the cellular level. PAT treatment reduced lipid accumulation, suppressed glucose and LDL uptake, inhibited lipid deposition and triglyceride synthesis, upregulated fatty acid oxidation-related genes (), and downregulated adipogenic/lipogenic genes ( and ) in hypertrophied 3T3-L1 adipocytes. Additionally, PAT treatment enhanced mitochondrial respiration and mass in differentiated adipocytes and alleviated inflammatory response in activated RAW 264.7 macrophages. Moreover, PAT treatment downregulated pro-inflammatory genes (, , , and ), suppressed lipopolysaccharide (LPS)-induced increase in inflammatory mediators (IL-6, TNF-α, and NO), and restored mitochondrial oxidative function in LPS-stimulated macrophages by improving oxygen consumption and mitochondrial integrity and suppressing ROS generation. Overall, these findings suggest a potential for PAT in the prevention of lipid accumulation and inflammation-related disorders.

摘要

展青霉素(PAT)是一种在腐烂的梨果中发现的天然霉菌毒素。尽管已经对PAT进行了一些毒理学研究,但最近的研究突出了其抗癌和抗真菌作用。然而,尚未有研究考察PAT在其他代谢性疾病中的作用及分子机制。肥胖是一种由食物摄入过多和生活方式异常引起的慢性疾病,会导致低度炎症。因此,本研究旨在阐明PAT在细胞水平上对肥胖的影响。PAT处理可减少脂质积累,抑制葡萄糖和低密度脂蛋白摄取,抑制脂质沉积和甘油三酯合成,上调肥大的3T3-L1脂肪细胞中脂肪酸氧化相关基因(),并下调脂肪生成/脂质生成基因(和)。此外,PAT处理可增强分化脂肪细胞中的线粒体呼吸和质量,并减轻活化的RAW 264.7巨噬细胞中的炎症反应。此外,PAT处理可下调促炎基因(、、、和),抑制脂多糖(LPS)诱导的炎症介质(IL-6、TNF-α和NO)增加,并通过改善氧气消耗和线粒体完整性以及抑制活性氧生成来恢复LPS刺激的巨噬细胞中的线粒体氧化功能。总体而言,这些发现表明PAT在预防脂质积累和炎症相关疾病方面具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/287e5b274129/antioxidants-12-01750-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/15ae00454414/antioxidants-12-01750-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/3f31c3856b49/antioxidants-12-01750-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/16cdd6560d7f/antioxidants-12-01750-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/0dd8b32cc4b0/antioxidants-12-01750-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/98767e7cdd2b/antioxidants-12-01750-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/a597f3c75f79/antioxidants-12-01750-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/c5158707faba/antioxidants-12-01750-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/e5da523dcf58/antioxidants-12-01750-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/287e5b274129/antioxidants-12-01750-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/15ae00454414/antioxidants-12-01750-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/3f31c3856b49/antioxidants-12-01750-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/16cdd6560d7f/antioxidants-12-01750-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/0dd8b32cc4b0/antioxidants-12-01750-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/98767e7cdd2b/antioxidants-12-01750-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/a597f3c75f79/antioxidants-12-01750-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/c5158707faba/antioxidants-12-01750-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/e5da523dcf58/antioxidants-12-01750-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b902/10526082/287e5b274129/antioxidants-12-01750-g009.jpg

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