High-Fat Diet Related Lung Fibrosis-Epigenetic Regulation Matters

Abstract

Pulmonary fibrosis (PF) is an interstitial lung disease characterized by the destruction of the pulmonary parenchyma caused by excessive extracellular matrix deposition. Despite the well-known etiological factors such as senescence, aberrant epithelial cell and fibroblast activation, and chronic inflammation, PF has recently been recognized as a metabolic disease and abnormal lipid signature was observed both in serum and bronchoalveolar lavage fluid (BALF) of PF patients and mice PF model. Clinically, observational studies suggest a significant link between high-fat diet (HFD) and PF as manifested by high intake of saturated fatty acids (SFAs) and meat increases the risk of PF and mice lung fibrosis. However, the possible mechanisms between HFD and PF remain unclear. In the current review we emphasize the diversity effects of the epigenetic dysregulation induced by HFD on the fibrotic factors such as epithelial cell injury, abnormal fibroblast activation and chronic inflammation. Finally, we discuss the potential ways for patients to improve their conditions and emphasize the prospect of targeted therapy based on epigenetic regulation for scientific researchers or drug developers.

Metabolic memory: mechanisms and diseases

“…Moreover, a high-fat diet could promote the resistance of lung fibroblasts to apoptosis by inhibiting the expression of the death receptor Fas (also called CD95), leading to the progression of pulmonary fibrosis. 251 The Fas promoter in fibroblasts from the murine model of pulmonary fibrosis displayed a reduction in histone acetylation and an increase in H3K9me3, which correlated with elevated expression of HDAC2 and HDAC4. 252 A high-fat diet has also been shown to induce H4K16ac accumulation, leading to pro-fibrotic gene overexpression and collagen deposition in lung fibroblasts.…”

Glycolysis Reprogramming in Idiopathic Pulmonary Fibrosis: Unveiling the Mystery of Lactate in the Lung

“…When lactate binds to GPR81, it can inhibit the lipolysis process in adipocytes through G protein-mediated signaling [ 189 , 190 ]. Interestingly, in IPF lungs, elevated lactate levels are accompanied by dysregulation of lipid metabolism, and the accumulation of lipids in the lungs promotes the progression of IPF [ 191 , 192 , 193 ]. This easily leads to the hypothesis that the elevation of lactate in IPF may contribute to the dysregulation of lipid metabolism in the lungs through its binding to GPR81.…”

Tangeretin attenuates bleomycin-induced pulmonary fibrosis by inhibiting epithelial-mesenchymal transition via the PI3K/Akt pathway

“…Pulmonary fibrosis (PF) is a chronic and lethal lung disease that is characterized by the excessive deposition of extracellular matrix (ECM), resulting in impaired gas exchange and lung function ( Moss et al, 2022 ; C; Wang and Yang, 2022 ; J; Yang et al, 2033a ). The most prevalent form of PF is idiopathic pulmonary fibrosis, which has a bleak prognosis and a median survival rate of 2.5–3.5 years following diagnosis ( Strongman et al, 2018 ).…”

“…Previous studies have demonstrated that Tanis able to prevent podocyte injury and renal fibrosis by effectively blocking glucose-induced oxidative stress and hypoxia-induced EMT in podocytes ( Kang et al, 2020 ). In addition, Tan effectively suppressed the activation of JAK2/STAT3, Wnt, and EGFR signaling pathways, as well as lung fibroblast activation (F. Yang J. et al, 2023 ; D; Shao et al, 2022 ). However, the potential mechanism of Tan in the treatment of pulmonary fibrosis remains incompletely understood.…”