Effect of early-life exposure to environmental risk factors on adult MASLD: Insights from DOHaD perspective

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, affecting approximately 30% of the adult population. Growing evidence supports the developmental origins of liver diseases, with early-life exposure to environmental chemicals emerging as a critical risk factor for MASLD in adulthood. Early-life exposure to environmental chemicals may exert a "programming effect" on hepatic development and metabolic function by disrupting nuclear receptor signaling, impairing mitochondrial homeostasis, inducing epigenetic reprogramming, and mediating liver-extrahepatic organ crosstalk, thereby significantly increasing the risk of MASLD in adulthood. Furthermore, paternal exposure has been shown to affect offspring hepatic metabolism through transgenerational epigenetic mechanisms. From the perspective of the Developmental Origins of Health and Disease (DOHaD) theory, this review summarizes environmental risk factors that impair hepatic metabolic function in adulthood and their underlying mechanisms.