Lipid droplet-organelle communication: A new perspective on AFB1-induced lipotoxicity in chicken hepatocytes and the protective effect of curcumin

Aflatoxin contamination in food and feed is prevalent worldwide and exposure to Aflatoxin B1 (AFB1) can lead to significant lipid accumulation in hepatocytes. However, the underlying mechanism by which curcumin mitigates AFB1-induced hepatotoxicity in chickens remains unclear. In this study, primary chicken embryonic hepatocytes (CEHs) were selected as the experimental model and divided into 1) control, 2) AFB1, 3) AFB1+Cur, and 4) curcumin alone group. AFB1 dose-dependently reduced cell viability, whereas curcumin enhanced it. AFB1 induced severe lipid droplets (LDs) accumulation (confirmed by staining and electron microscopy) and disrupted cellular structures. Transcriptome and proteome analyses further demonstrated that AFB1-induced lipotoxicity both in vivo and in vitro . In contrast, curcumin reversed these effects. Under AFB1 exposure, a significant up-regulation of fatty acid synthesis genes (PTGS2, FAS) and down-regulation of the fatty acid metabolism related gene CPT1A in CEHs were observed. AFB1 also impaired autophagy (decreased p62, increased LC3B/ATG9a), damaged lysosomes (downregulated NPC1/LAMP1, upregulated mTOR/LGALS1a), altered mitochondrial dynamics (upregulated DRP1/FIS1/MFN1, downregulated MFN2), and activated necroptosis (upregulated RIPK1/RIPK3/MLKL). Critically, curcumin co-treatment (AFB1+Cur) reversed these detrimental effects. Furthermore, AFB1+Cur significantly decreased LDs-mitochondria colocalization and increased LDs-lysosome colocalization compared to AFB1 alone group. This study suggests that the changes in lipid metabolism, oxidative stress and necroptosis caused by lipid drop-organelle communication may be a new perspective on AFB1-induced lipotoxicity in chicken hepatocytes and curcumin offers a potential treatment for protecting hepatocytes from lipotoxicity. Future directions should include chicken feeding trials assessing curcumin's ability to AFB1-induced hepatic steatosis and necroptosis under real-world exposure levels.