Fig. 1

Alterations in aging adipose tissue and the involvement of fat deposition in the occurrence and development of IPF. 1) During the aging process, excessive expansion of adipose tissue leads to hypoxia. This stimulates adipocytes and ATMs to secrete inflammatory chemokines, resulting in immune cell infiltration in aging adipose tissue. 2) Fibrosis in dysfunctional adipose tissue leads to lipotoxicity and an increased leptin/adiponectin ratio. This activates highly proinflammatory M1-type macrophages (M1 ATMs) through molecules such as leptin, PAI-1, FFA, and inflammatory cytokines, thereby exacerbating the inflammatory response. 3) Lipotoxicity and inflammation in aging adipose tissue leads to endoplasmic reticulum stress, mitochondrial dysfunction, apoptosis, autophagy and necrosis of AT2 cells. Subsequently, in the alveoli, cell debris, recruited immune cells, and foam cells (macrophages engulfing lipid droplets) participate in the inflammatory cascade response, resulting in fibroblast-to-myofibroblast (MYF) transformation and epithelial-mesenchymal transition (EMT). 4) Adipose factors such as Ang II, PAI-1, and S1P can also promote fibroblast-to-MYF transformation. 5) Lipotoxicity and inflammation not only promote the differentiation of LIFs into MYFs but also affect the supply of pulmonary surfactant precursors to AT2 cells. The figure was created using BioRender (www.biorender.com). Abbreviations: adipose tissue macrophages (ATMs), plasminogen activator inhibitor-1 (PAI-1), free fatty acids (FFA), alveolar epithelial type II cells (AT2), myofibroblast (MYF), epithelial-mesenchymal transition (EMT), Angiotensin II (Ang II), sphingosine-1-phosphate (S1P), lipofibroblasts (LIFs)