The emerging role of metabolism in fibrosis

Metabolism has emerged as a major driver of fibrotic diseases. Glycolytic shifts appear to be a key metabolic switch in stromal cells under fibrotic conditions regardless of aetiology. Glutaminolysis as well as glycolysis may be a therapeutic target in fibrosis. Immunometabolites exert antifibrotic effects and may be harnessed for therapeutic gain. The metabolic shift that cancer cells undergo towards aerobic glycolysis was identified as a defining feature in tumours almost 100 years ago; however, it has only recently become apparent that similar metabolic reprogramming is a key feature in other diseases – with fibrosis now entering the fray. In this perspective, an overview of the recent evidence implicating increased glycolysis and glutaminolysis as mediators of fibrosis is presented, with a particular emphasis on the novel therapeutic possibilities this introduces. Furthermore, the impact that metabolic reprogramming has on redox homeostasis is discussed, providing an insight into how this often-overlooked mechanism may drive the pathogenesis. The metabolic shift that cancer cells undergo towards aerobic glycolysis was identified as a defining feature in tumours almost 100 years ago; however, it has only recently become apparent that similar metabolic reprogramming is a key feature in other diseases – with fibrosis now entering the fray. In this perspective, an overview of the recent evidence implicating increased glycolysis and glutaminolysis as mediators of fibrosis is presented, with a particular emphasis on the novel therapeutic possibilities this introduces. Furthermore, the impact that metabolic reprogramming has on redox homeostasis is discussed, providing an insight into how this often-overlooked mechanism may drive the pathogenesis.