Palmitic Acid–Rich High-Fat Diet Exacerbates Experimental Pulmonary Fibrosis by Modulating Endoplasmic Reticulum Stress

Chu, Sarah G.; Villalba, Julian A.; Liang, Xiaoliang; Xiong, Kevin; Tsoyi, Konstantin; Ith, Bonna; Ayaub, Ehab; Tatituri, Raju V. V.; Byers, Derek E.; Hsu, Fong‐Fu; El–Chemaly, Souheil; Kim, Edy Y.; Shi, Yuanyuan; Rosas, Iván O.

doi:10.1165/rcmb.2018-0324oc

Cited by 75 publications

(56 citation statements)

References 45 publications

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“…Deletion of the CD36 lipid receptor abolishes these toxic effects, thus demonstrating that sensing of lipids by pulmonary epithelial cells can trigger endoplasmic reticulum stress, which in turn may facilitate the fibrotic response in lungs during lung injury. However, deletion of the CD36 lipid receptor abolishes these toxic effects 97 . Thus, targeting pulmonary metabolism may be an additional therapeutic option in patients with COVID-19, to promote their recovery and increase their likelihood of returning to their original health state before the infection (Fig.…”

Section: Antivirulence Metabolic Strategies To Block Pathogenic Signalsmentioning

confidence: 99%

A metabolic handbook for the COVID-19 pandemic

2020

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Section: Antivirulence Metabolic Strategies To Block Pathogenic Signalsmentioning

confidence: 99%

A metabolic handbook for the COVID-19 pandemic

2020

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“…The authors proposed that the increase in palmitic acid content resulted in profibrotic events such as increased TGFβ and apoptosis through increased intracellular generation of reactive oxygen species. Increased FA content, including palmitic acid has been encountered in IPF lungs [144,145], and treatment of cell cultures with palmitic acid triggered ER stress and apoptotic responses. In vivo, mice pretreated with 2-weeks of high fat diet (HFD) had higher collagen content upon bleomycin treatment.…”

Section: Lipids In Interstitial Lung Disease and Idiopathic Pulmonarymentioning

confidence: 99%

Alveolar lipids in pulmonary disease. A review

2020

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Lung lipid metabolism participates both in infant and adult pulmonary disease. The lung is composed by multiple cell types with specialized functions and coordinately acting to meet specific physiologic requirements. The alveoli are the niche of the most active lipid metabolic cell in the lung, the type 2 cell (T2C). T2C synthesize surfactant lipids that are an absolute requirement for respiration, including dipalmitoylphosphatidylcholine. After its synthesis and secretion into the alveoli, surfactant is recycled by the T2C or degraded by the alveolar macrophages (AM). Surfactant biosynthesis and recycling is tightly regulated, and dysregulation of this pathway occurs in many pulmonary disease processes. Alveolar lipids can participate in the development of pulmonary disease from their extracellular location in the lumen of the alveoli, and from their intracellular location in T2C or AM. External insults like smoke and pollution can disturb surfactant homeostasis and result in either surfactant insufficiency or accumulation. But disruption of surfactant homeostasis is also observed in many chronic adult diseases, including chronic obstructive pulmonary disease (COPD), and others. Sustained damage to the T2C is one of the postulated causes of idiopathic pulmonary fibrosis (IPF), and surfactant homeostasis is disrupted during fibrotic conditions. Similarly, surfactant homeostasis is impacted during acute respiratory distress syndrome (ARDS) and infections. Bioactive lipids like eicosanoids and sphingolipids also participate in chronic lung disease and in respiratory infections. We review the most recent knowledge on alveolar lipids and their essential metabolic and signaling functions during homeostasis and during some of the most commonly observed pulmonary diseases.

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“…Biosynthesis of palmitic acid (C16:0) and other long-chain saturated and unsaturated fatty acids is central to the generation of triglycerides, phospholipids, and sphingolipids with different fatty acid molecular species that dictate their function and metabolic fate. Cellular levels of free fatty acids are very low in tissues; however, elevated levels of palmitic acid were detected in the lungs of patients with IPF compared with control subjects [24]. Palmitic acid-rich high fat diet-induced epithelial cell death and a prolonged pro-apoptotic endoplasmic reticulum (ER) stress response after bleomycin-induced lung fibrosis.…”

Section: Fatty Acids and Fatty Acid Elongation In Pulmonary Fibrosismentioning

confidence: 99%

Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

Suryadevara

Ramchandran

Kamp

et al. 2020

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology characterized by distorted distal lung architecture, inflammation, and fibrosis. The molecular mechanisms involved in the pathophysiology of IPF are incompletely defined. Several lung cell types including alveolar epithelial cells, fibroblasts, monocyte-derived macrophages, and endothelial cells have been implicated in the development and progression of fibrosis. Regardless of the cell types involved, changes in gene expression, disrupted glycolysis, and mitochondrial oxidation, dysregulated protein folding, and altered phospholipid and sphingolipid metabolism result in activation of myofibroblast, deposition of extracellular matrix proteins, remodeling of lung architecture and fibrosis. Lipid mediators derived from phospholipids, sphingolipids, and polyunsaturated fatty acids play an important role in the pathogenesis of pulmonary fibrosis and have been described to exhibit pro- and anti-fibrotic effects in IPF and in preclinical animal models of lung fibrosis. This review describes the current understanding of the role and signaling pathways of prostanoids, lysophospholipids, and sphingolipids and their metabolizing enzymes in the development of lung fibrosis. Further, several of the lipid mediators and enzymes involved in their metabolism are therapeutic targets for drug development to treat IPF.

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Palmitic Acid–Rich High-Fat Diet Exacerbates Experimental Pulmonary Fibrosis by Modulating Endoplasmic Reticulum Stress

Cited by 75 publications

References 45 publications

A metabolic handbook for the COVID-19 pandemic

A metabolic handbook for the COVID-19 pandemic

Alveolar lipids in pulmonary disease. A review

Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

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