Advancing fatty liver research in dairy cows: Development of a bovine liver organoid model

Aiming to enhance disease modeling and drug screening for fatty liver disease, a bovine liver organoid model was developed using R-spondin-1 conditioned medium. Adult stem cells from calf liver were cultured and differentiated into organoids, exhibiting specific liver markers and functions. These organoids, treated by a mixture of oleic acid and palmitic acid, demonstrated significant accumulation of total cholesterol and triglycerides, effectively mimicking the fatty liver condition observed in high-yielding dairy cows during the periparturient period. Treatment with 5 natural compounds (silymarin, gastrodin, cordycepin, curcumin, and polydatin) and a positive control (atorvastatin) showed significantly reduced inflammation and lipid accumulation in the bovine liver organoid. Specifically, anti-inflammatory factors were upregulated, pro-inflammatory factors downregulated, and genes related to lipid synthesis were downregulated. Collectively, the application of organoid technology exhibits its potential in simulating disease mechanisms and evaluating therapeutic interventions, notably reducing the need for live animal experiments. Our study establishes a bovine liver organoid model and validates its effectiveness as a tool for advancing disease research and pharmaceutical development.