Linoleic Acid Promotes Mitochondrial Biogenesis and Alleviates Acute Lung Injury

• DOI: 10.1111/crj.70004
• Publication Date: 2024-09-24T04:01:03Z
• Authors: Jie Liu; Yu Jiang; Qiuhong Zhang; Yin Qin; Kexin Li; Yu Xie; Tingting Zhang; Xiaoliang Wang; Xi Yang; Li Zhang; Gang Liu
• Keywords: linoleic acid; Lipopolysaccharides; Male; mitochondrial biogenesis; Organelle Biogenesis; RC705-779; lipopolysaccharide; Acute Lung Injury; Mitochondria; Linoleic Acid; Diseases of the respiratory system; Mice; Disease Models, Animal; Oxidative Stress; acute lung injury; inflammation; PGC‐1α; Animals; Original Article; Bronchoalveolar Lavage Fluid

ABSTRACTIntroductionAcute lung injury (ALI) is a critical and lethal medical condition. This syndrome is characterized by an imbalance in the body's oxidation stress and inflammation. Linoleic acid (LA), a polyunsaturated fatty acid, has been extensively studied for its potential health benefits, including anti‐inflammatory and antioxidant activities. However, the therapeutic effects of LA on ALI remain unexplored.MethodsLipopolysaccharide (LPS), found in gram‐negative bacteria's outer membrane, was intraperitoneally injected to induce ALI in mice. In vitro model was established by LPS stimulation of mouse lung epithelial 12 (MLE‐12) cells.ResultsLA treatment demonstrated a significant amelioration in LPS‐induced hypothermia, poor state, and pulmonary injury in mice. LA treatment resulted in a reduction in the concentration of bronchoalveolar lavage fluid (BALF) protein and an increase in myeloperoxidase (MPO) activity in LPS‐induced mice. LA treatment reduced the generation of white blood cells. LA treatment reduced cell‐free (cfDNA) release and promote adenosine triphosphate (ATP) production. LA increased the levels of superoxide dismutase (SOD) and glutathione (GSH) but decreased the production of malondialdehyde (MDA). LA treatment enhanced mitochondrial membrane potential. LA attenuated LPS‐induced elevations of inflammatory cytokines in both mice and cells. Additionally, LA exerted its protective effect against LPS‐induced damage through activation of the peroxisome proliferator‐activated receptor γ coactivator l alpha (PGC‐1α)/nuclear respiratory factor 1 (NRF1)/transcription factor A of the mitochondrion (TFAM) pathway.ConclusionLA may reduce inflammation and stimulate mitochondrial biogenesis in ALI mice and MLE‐12 cells.