Allyl isothiocyanate ameliorates metabolic dysfunction-associated steatotic liver disease via vitamin D receptors in hepatocytes.

BACKGROUND: Prior studies indicate that allyl isothiocyanate (AITC) alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). The vitamin D receptor (VDR) is known to exert protective effects in MASLD; however, whether AITC alleviates MASLD through VDR remains unclear. AIM: To clarify the function and underlying mechanisms of AITC in MASLD via VDR. METHODS: AML-12 cells were exposed to 300 μM palmitate acid (PA) for 24 hours to establish an in vitro MASLD model, followed by treatment with AITC (20 μM). We quantified intracellular lipid content using oil red O staining and biochemical triglyceride assays, and measured the expression of key regulators of hepatic de novo lipogenesis, fatty-acid (FA) β-oxidation, and insulin-resistance-related signaling by immunoblotting and quantitative real-time polymerase chain reaction. RESULTS: To establish an in vitro MASLD model, AML-12 cells were treated with 300 μM PA for 24 hours. In this model, AITC significantly reduced protein levels associated with lipid synthesis and insulin resistance while upregulating those involved in FA β-oxidation. AITC enhanced VDR expression and increased the expression of hepatocyte nuclear factor 4 alpha (HNF-4α) and the downstream targets microsomal triglyceride transfer protein (MTTP) and apolipoprotein B (ApoB). These changes mitigated PA-induced lipid accumulation, alleviated insulin resistance, and stimulated FA β-oxidation. Additionally, vitamin D further enhanced the therapeutic effects of AITC on MASLD. CONCLUSION: AITC provides a robust molecular basis for improving MASLD by activating hepatic VDR and driving the downstream HNF-4α/MTTP/ApoB signaling pathway. This pathway reduces hepatic lipid accumulation, promotes FA β-oxidation, and improves insulin resistance, establishing AITC as a promising treatment for MASLD.