Lipid Droplet Accumulation and Increased DGAT1 Expression During the Progression of Experimental Silicosis

Introduction: Silicosis is a progressive fibrotic pneumoconiosis caused by inhalation of respirable crystalline silica, characterized by persistent inflammation, granuloma formation, and pulmonary fibrosis. Emerging evidence suggests that alterations in lipid metabolism contribute to the regulation of inflammatory responses; however, their role in silicosis pathophysiology remains poorly understood.

Objective: To investigate lipid droplet (LD) accumulation and Diacylglycerol O-acyltransferase 1 (DGAT1) expression during experimental silicosis.

Methodology: Male Swiss-Webster mice received intranasal silica (10 mg/mouse) and were euthanized 7 or 28 days after exposure. LDs were analyzed in frozen lung sections stained with Oil Red O and quantified using ImageJ. DGAT1 expression was assessed in lung tissue. Procedures were approved by the Ethics Committee of the Oswaldo Cruz Institute/FIOCRUZ (L001/19-A6).

Results: Oil Red O staining showed increased LD accumulation in both acute and chronic phases of silicosis. Morphometric analysis confirmed a significant increase in LD area, particularly within granulomatous regions during the chronic phase. These findings occurred in a model characterized by acute inflammatory cell recruitment followed by persistent inflammation, granuloma formation, collagen deposition, and fibrosis. DGAT1 expression was also significantly increased, indicating enhanced LD biogenesis after silica exposure.

Conclusion: Lipid droplet accumulation is an early and sustained event during progression of experimental silicosis, suggesting these organelles contribute to both inflammatory and fibrotic responses. Increased DGAT1 expression further supports the involvement of altered lipid metabolism in disease pathogenesis, highlighting the DGAT1/lipid droplet axis as a promising therapeutic target for silicosis.

Financial support: FIOCRUZ, FAPERJ, CNPq.