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IF: 5.2
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L-Histidine attenuates NEFA-induced inflammatory responses by suppressing Gab2 expression

Published:4 May 2024 DOI: 10.1016/j.lfs.2024.122672 PMID: 38705456
Mengze Li , Huiying Wang , Hanjun Ren , Tao Zhang , Guoyan Zhou , Shiyi Chen , Jie Wang , Xianbo Jia , Songjia Lai , Xiang Gan , Wenqiang Sun

Abstract

Non-esterified fatty acids (NEFAs), key to energy metabolism, may become pathogenic at elevated levels, potentially eliciting immune reactions. Our laboratory's findings of reduced L-histidine in ketotic states, induced by heightened NEFA concentrations, suggest an interrelation with NEFA metabolism. This observation necessitates further investigation into the mitigating role of L-histidine on the deleterious effects of NEFAs. Our study unveiled that elevated NEFA concentrations hinder the proliferation of Bovine Mammary Epithelial Cells (BMECs) and provoke inflammation in a dose-responsive manner. Delving into L-histidine's influence on BMECs, RNA sequencing revealed 2124 genes differentially expressed between control and L-histidine-treated cells, with notable enrichment in pathways linked to proliferation and immunity, such as cell cycle and TNF signaling pathways. Further analysis showed that L-histidine treatment positively correlated with an increase in EdU-555-positive cell rate and significantly suppressed IL-6 and IL-8 levels (p?<?0.05) compared to controls. Crucially, concurrent treatment with high NEFA and L-histidine normalized the number of EdU-555-positive cells and cytokine expression to control levels. Investigating the underlying mechanisms, Gab2 (Grb2-associated binder 2) emerged as a central player; L-histidine notably reduced Gab2 expression, while NEFA had the opposite effect (p?<?0.05). Gab2 overexpression escalated nitric oxide (NO) production and IL6 and IL8 expression. However, L-histidine addition to Gab2-overexpressing cells resulted in NO concentrations indistinguishable from controls. Our findings collectively indicate that L-histidine can counteract NEFA-induced inflammation in BMECs by inhibiting Gab2 expression, highlighting its therapeutic potential against NEFA-related metabolic disturbances.

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L-Histidine 71-00-1 C6H9N3O2 868 suppliers $7.00-$21470.00
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NITRIC OXIDE 10102-43-9 NO* 58 suppliers $479.00-$9930.00
MOUSE IL-6 36 suppliers $75.00-$591.00
GAB2 18 suppliers Inquiry
Sheep non-ester fatty acid (NEFA) ELISA Kit 4 suppliers Inquiry

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