TABLE 1.

Summary of studies linking obesity and pulmonary fibrosis.

Author (year)	Study model	Main findings associated with HFD
Ge et al. (2013)	SD/HFD feeding of C57BL/6 mice for 12 weeks (60% kcal from fat), followed by challenge with cockroach allergen.	Elevated lung TGF-β, PAI-1 expression, lung collagen expression, and decreased lung function. Infiltrated immune cells, epithelial, and endothelial cells were found as a major source of TGF-β expression.
Park et al. (2019)	SD/HFD feeding of C57BL/6 mice for 12 weeks (60% kcal from fat).	Increased insulin resistance, AHR, peribranchial and perivascular fibrosis, and macrophages in the BAL; insulin stimulates TGF-β1 expression in bronchial epithelial cells in vivo and in vitro; Anti-TGF-β1 antibody attenuated HFD-induced lung fibrosis.
Hegab et al. (2021)	SD/HFD feeding (60% kcal from fat) for 4 weeks, followed by bleomycin challenge and examine after 3, 6, and 9 weeks.	No significant differences in inflammation and fibrosis severity between SD and HFD-fed flies after 3 weeks; HFD-induced a delay in alveolar repair and fibrosis resolution at 6 weeks following bleomycin treatment.
Naura et al. (2009)	SD/HFD feeding for 12 weeks (42% kcal from fat) in ApoE−/− mice; direct intratracheal TNF-α (100 ng/mouse) administration in ApoE−/− mice for 6 and 24 h.	Elevated TNF-α, IFN-γ, and MIP-1α and increased tissue distribution of TGF-β, recruitment of monocytes and macrophages, subepithelial, and peri-vascular collagen deposition and thickening in lungs of ApoE−/− mice. TNF-α induced proinflammatory cytokines similar as that of HFD and induced MCP-1, TGF–β1, IL-1β, and collagen type 1 expression.
Yu et al. (2013)	HFD (Lieber-DeCarli liquid diet) feeding of male Sprague-Dawley (SD) rats for 8 weeks	Increased TGF-β expression in lung tissues and deposition of collagen fibers at alveolar septa in HFD group.
Han et al. (2021)	SD/HFD feeding of C57BL/6 mice for 12 weeks (60% kcal from fat)	Increased BAL cell numbers; elevated lung TGF-β; increased collagen deposition, hydroxyproline content, and fibrosis; and decreased serum 25-hydroxyl vitamin D in mice received HFD.
Vedova et al. (2019)	SD/HFD (22% chicken fat) and with or without 10% fructose for 16 weeks.	HFD plus fructose additively enhanced pulmonary inflammation, oxidative stress, and pro-fibrotic changes.
Chu et al. (2019)	SD/HFD feeding of C57BL/6 mice (42% kcal from fat) for 2 weeks followed by bleomycin challenge (1.2 mg/kg) via oral aspiration. Lung tissues examined at 3, 7, and 21 days after bleomycin.	HFD for 5 weeks did not induce hydroxyproline in the lung, however, it significantly enhanced bleomycin-increased hydroxyproline content, mRNA levels of collagen 1 and fibronectin at 21 days. HFD induced apoptosis and a prolonged ER stress after bleomycin.
Baack et al. (2016)	Female SD rats fed HFD (40% kcal from fat) 4 weeks before mating, offspring examined at 3 weeks of age.	No difference in lung fibrosis in offspring at 3 weeks of age; increased perinatal mortality and decreased pulmonary vessels in maternal HFD-exposed offspring.
Song et al. (2015)	Female SD rats were fed a SD/HFD for 8 weeks, then bred with normal male rats, maintained on SD/HFD during pregnancy and lactation.	Maternal HFD exposed offspring showed significantly increased pulmonary inflammatory infiltration, collagen deposition, and increased TGF-β and α-smooth muscle actin expression in the lung.

Note: AHR, airway hyperreactivity; BAL, bronchoalveolar lavage; SD, standard diet; HFD, high-fat diet.