As an important
organophosphate flame retardant,
tris(1-chloro-2-propyl)phosphate (
TCPP) is ubiquitous in the environment leading to inevitable human exposure. However, there is a paucity of information regarding its acute/chronic effects on
obesity,
lipid homeostasis, and
hepatocellular carcinoma, especially regarding the underlying molecular mechanisms in humans. Herein, we investigated the effects of
TCPP exposure (5-25 mg/L) on
lipid homeostasis in larval and adult zebrafish (Danio rerio).
TCPP exposure caused remarkable lipid-metabolism dysfunction, which was reflected in
obesity and excessive
lipid accumulation in zebrafish liver. Mechanistically,
TCPP induced the over-expression of adipogenesis genes and suppressed the expression of
fatty-acid β-oxidation genes. Consequently, excess
lipid synthesis and deficient expenditure triggered oxidative damage and an
inflammation response by disrupting the
antioxidant system and over-expressing proinflammatory
cytokine. Based on high-throughput transcriptome sequencing, we found that
TCPP exposure led to enrichment of several pathways involved in lipid metabolism and
inflammation, as well as several genes related to pathways of
cancer. Notably, increasing expressions of Ki-67 and 53BP1
proteins, which are reliable
biomarkers for recognition and risk prediction of cellular proliferation in
cancer cells, were observed in liver tissues of adult zebrafish. These results imply that chronic
TCPP exposure triggers a potential risk of hepatocellular
carcinogenesis (HCC) progression. Collectively, these findings offer new insights into our mechanistic understanding for the health effects of organophosphorus
flame retardants on humans.