Unveiling the biological activities of the microbial long chain hydroxy fatty acids as dual agonists of GPR40 and GPR120

IF 5.4 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Biomaterials Science & Engineering Pub Date : 2024-11-12 DOI:10.1016/j.foodchem.2024.142010

Yeeun Park, Ji-Min Woo, Jaeeun Shin, Myunghae Chung, Eun-Ji Seo, Sung-Joon Lee, Jin-Byung Park

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Abstract

The physiological functions of various fatty acid-originating metabolites from foods and fermented products remained mostly untouched. Thereby, this study examined the biological activities of hydroxy fatty acids as agonists of G protein-coupled receptors (i.e., GPR40 and GPR120), which are derived from long-chain fatty acids (e.g., oleic acid and linoleic acid) by microbiota. Cell-based Ca²⁺ mobilization assays and in silico docking simulations revealed that not only the degree of unsaturation but also the number and position of hydroxyl groups played a key role in their agonist activities. For instance, 8,11-dihydroxyoctadec-9Z-enoic acid exhibited significantly greater Ca²⁺ response in the GPR40/GPR120-expressing cells as compared to the endogenous agonists (e.g., linoleic acid and docosahexaenoic acid), forming hydrogen bond interactions with residues in the ligand-binding pockets of receptors. This study will contribute to understanding the relationships between fatty acid structures and agonist activities.

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揭示微生物长链羟基脂肪酸作为 GPR40 和 GPR120 双激动剂的生物活性

食品和发酵产品中各种脂肪酸代谢产物的生理功能大多仍未得到研究。因此，本研究考察了羟基脂肪酸作为 G 蛋白偶联受体（即 GPR40 和 GPR120）激动剂的生物活性。基于细胞的 Ca2+ 调动试验和硅学对接模拟显示，不仅是不饱和程度，羟基的数量和位置也对它们的激动剂活性起着关键作用。例如，与内源性激动剂（如亚油酸和二十二碳六烯酸）相比，8,11-二羟基十八碳-9Z-烯酸在 GPR40/GPR120 表达细胞中表现出明显更强的 Ca2+ 反应，与受体配体结合袋中的残基形成氢键相互作用。这项研究将有助于了解脂肪酸结构与激动剂活性之间的关系。

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来源期刊

ACS Biomaterials Science & Engineering Materials Science-Biomaterials

CiteScore

10.30

自引率

3.40%

发文量

413

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