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Environmentally relevant lanthanum chloride exposure induces hepatic steatosis in zebrafish larvae via PPARα-dependent ApoB suppression

Year: 2026

Type: article

Abstract: Lanthanum (La), the second most produced rare earth element, is detected in various environmental and human samples. Epidemiological studies have reported a strong association between La exposure and liver injury. However, the effects of early La exposure on liver development and underlying mechanisms remain limited. Here, we evaluate the hepatotoxicity of LaCl3 at environmentally relevant concentrations using zebrafish larvae. Embryonic LaCl3 exposure causes concentration-dependent hepatic steatosis, which cannot be reversed after exposure cessation. Metabolomic profiling reveals that very-low-density lipoprotein (VLDL) and its multiple downstream metabolites are consistently downregulated upon LaCl3 treatment, together with increased triglycerides (TG) level, indicating impaired TG-VLDL biosynthesis. In addition, transcriptomics suggest that genes related to the PPARα signaling pathway are significantly downregulated, especially those involved in TG-VLDL biosynthesis (mttp and all apob subtypes). Further studies show that LaCl3 can inhibit the transcriptional regulatory activity of PPARα. The upregulation of the PPARα signaling pathway corresponding genes of ppara, mttp, and apob effectively rescues LaCl3-induced liver impairments. Subsequently, a subcellular localization assay finds that increased ApoB degradation in the endoplasmic reticulum contributes to LaCl3-triggered lipid droplet accumulation. Overall, our findings fill critical research gaps regarding LaCl3-induced hepatotoxicity and provide important evidence for the environmental risk assessment of La. Early-life exposure to environmentally relevant lanthanum chloride (LaCl3) induces persistent hepatic steatosis in zebrafish by suppressing PPAR α and accelerating ApoB degradation, thereby impairing TG-VLDL biogenesis, which provides mechanistic evidence to inform environmental risk assessment of lanthanum.

Source: Communications Biology

DOI: 10.1038/s42003-026-09697-6