Protective effect of vitamin D on high-fat-diet-induced metabolic dysfunction-associated steatotic liver disease in mice

Abstract

Background: Genetics, inflammation, and nutrition contribute to the pathogenesis of metabolic dysfunction–associated steatotic liver disease (MASLD).

Aim: This preclinical study evaluated the protective effect of vitamin D supplementation against high-fat-diet–induced MASLD in a mouse model and compared physiological, inflammatory, and molecular responses across high-fat and low-fat dietary regimens, with and without vitamin D co-administration.

Methods: Forty-five healthy male albino Swiss mice (aged 6 weeks; 30 ± 10 g) were randomly assigned to five groups (n = 9 each): control (standard diet), HFD (high-fat diet), HFD + vitamin D, LFD (low-fat diet), and LFD + vitamin D. Vitamin D (20 000 IU/kg/week) was administered via drinking water for 12 weeks. Body weight, visceral adiposity, and liver indices were recorded, while serum biochemical markers, inflammatory cytokines, and expression of Toll-like receptor 7 (TLR7) and microRNA-155 (miR-155) were analyzed at endpoint.

Results: HFD-fed mice exhibited marked increases in ALT (51.44 ± 9.68 U/L), AST (56.67 ± 13.29 U/L), ALP (135.01 ± 16.19 U/L), AFP (28.56 ± 5.31 ng/mL), CRP (20.87 ± 5.56 mg/L), total cholesterol (225.00 ± 27.16 mg/dL), LDL (137.56 ± 28.66 mg/dL), and triglycerides (210.56 ± 28.71 mg/dL), accompanied by reduced HDL (30.24 ± 9.86 mg/dL) compared with controls. Pro-inflammatory cytokines TNF-α (28.33 ± 2.96 pg/mL), IL-6 (121.78 ± 8.98 pg/mL), and the expression of TLR7 (2.92 ± 0.83) and miR-155 (2.75 ± 0.77) were significantly elevated relative to normal-fed mice (miR-155: 0.84 ± 0.26). Vitamin D supplementation significantly ameliorated these metabolic and inflammatory disturbances.

Conclusions: Vitamin D supplementation mitigated HFD-induced hepatic injury, dyslipidemia, and inflammatory activation by modulating the miR-155/TLR7 axis. These findings highlight vitamin D as a potential adjunctive strategy for preventing or attenuating MASLD progression under high-fat dietary conditions.