Lipoic Acid Ameliorates Lipopolysaccharide-Induced Inflammation via Inhibition of Glycolysis in RAW264.7 Macrophages

Sep 30, 2026

Uploaded by Sarah

Background: Sustained pulmonary inflammation significantly contributes to lung carcinogenesis. Macrophages drive inflammatory persistence through metabolic reprogramming, shifting from oxidative phosphorylation to glycolysis during activation; the coupling between metabolism and macrophage polarization remains incompletely understood. Objective: Evaluate how lipoic acid suppresses inflammation by modulating immunometabolism in activated macrophages. Methods: LPS-stimulated RAW264.7 cells and a murine acute lung injury model were used, with cytokines measured by qPCR, ELISA, and Western blot; metabolism assessed by Seahorse XF via OCR and ECAR.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Introduction

Background and significance of pulmonary inflammation

Macrophage polarization and immunometabolic reprogramming

Immunity, Inflammation and Disease ORIGINAL ARTICLE Lipoic Acid Ameliorates Lipopolysaccharide‐Induced Inflammation via Inhibition of Glycolysis in RAW264.7 Macrophages Liduo Yue1 | Kai Wang2 | Rongyuan Wang3 | Linbei Lu1 | Lihong Fan1,4 1Shanghai Tenth People′s Hospital, Institute of Energy Metabolism and Health, Tongji University School of Medicine, Shanghai, China | 2Shanghai YangZhi Rehabilitation Hospital （Shanghai Sunshine Rehabilitation Center), Tongji University, Shanghai, People's Republic of China | 3School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China | 4Department of Pulmonology, Sixth People′s Hospital affiliated to Shanghai Jiaotong University, Shanghai, China Correspondence: Liduo Yue ([2216443774@qq.com](2216443774@qq.com)) | Lihong Fan ([1300008@tongji.edu.cn](1300008@tongji.edu.cn)) Received: 9 April 2025 | Revised: 5 December 2025 | Accepted: 15 December 2025 Funding: Innovative Flagship Hospital for Integrated Traditional Chinese and Western Medicine, Grant/Award Number: ZY(2021‐2023)‐0205‐05); SARS special Grant for traditional Chinese medicine, Grant/Award Number: 2023ZYLCY Keywords: anti‐inflammation | HIF1α | lipoic acid | macrophage ABSTRACT Background: Sustained pulmonary inflammation contributes significantly to lung carcinogenesis. Macrophages play a pivotal role in perpetuating inflammatory responses, undergoing a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis upon activation. The interplay between metabolic reprogramming and macrophage polarization remains poorly defined. The objective of this study is to examines the anti‐inflammatory mechanism of lipoic acid (LA), focusing on its ability to modulate immunometabolism in activated macrophages. Methods: We utilized lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophages and a murine acute lung injury (ALI) model to evaluate the anti‐inflammatory effects of LA. Inflammatory cytokine expression was assessed by qPCR, ELISA, and Western blot. Metabolic profiling was performed using Seahorse XF technology to measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), evaluating glycolytic and oxidative metabolic functions. Results: This study systematically elucidates the molecular mechanism by which LA modulates macrophage inflammatory responses through targeting the HIF1α/glycolysis axis. The main findings are as follows: (1) In LPS‐induced RAW264.7 macrophages, LA treatment significantly inhibited the expression of M1 macrophage markers (iNOS, CD86) and the secretion of proinflammatory cytokines (IL‐1β, IL‐6, etc.) . (2) LA effectively reduced the expression of GSDMD, the key executor of pyroptosis, demonstrating its inhibitory effect on macrophage pyroptosis. (3) Metabolic analysis revealed that LA reversed LPS‐ induced metabolic reprogramming by decreasing the ECAR and increasing the OCR, thereby suppressing glycolysis. (4) Mechanistic studies showed that siRNA‐mediated knockdown of HIF1α replicated both the anti‐inflammatory and metabolic regulatory effects of LA, confirming HIF1α as the key target in this pathway. (5) In an ALI mouse model, LA treatment significantly reduced HIF1α expression in lung tissues and effectively alleviated inflammatory responses, further validating the proposed mechanism. | Liduo Yue, Kai Wang, Rongyuan Wang contributed equally to this study. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2026 The Author(s) . Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. | Immunity, Inflammation and Disease, 2026; 14:e70313 1 of 15 [https://doi.org/10.1002/iid3.70313](https://doi.org/10.1002/iid3.70313) Conclusion: LA exerts potent anti‐inflammatory effects by targeting HIF1α‐mediated metabolic reprogramming in macrop

FAQs

What is the main research goal of the study?

To examine the anti-inflammatory mechanism of lipoic acid by focusing on how it modulates immunometabolism in activated macrophages.

How were anti-inflammatory effects of lipoic acid evaluated?

RAW264.7 macrophages stimulated with lipopolysaccharide and a murine acute lung injury model were used, and inflammatory cytokines were measured by qPCR, ELISA, and Western blot.

What mechanism links lipoic acid to reduced inflammation?

The study reports that lipoic acid targets the HIF1α/glycolysis axis, inhibiting glycolysis, reducing inflammatory markers, and limiting macrophage pyroptosis.

Sep 30, 2026

Uploaded by Sarah