Abstract
BACKGROUND: Dairy products may mitigate metabolic dysfunction-associated steatotic liver disease (MASLD) progression, but the role of dairy fat is unclear. OBJECTIVES: This animal trial compared MASLD-related outcomes after feeding nonfat milk (NFM) or whole-fat milk (WFM) in a high-fat diet (HFD)-induced MASLD mouse model. METHODS: Male C57BL/6N mice were fed a HFD (45% kcal fat; n = 40) for 9 wk. During the last 8 wk, 2 randomly selected groups additionally consumed 0.425 mL NFM (0 g% fat; n = 8) or WFM (3.25 g% fat; n = 12), from a small dish, 5 d/wk. A low-fat diet group (10% kcal fat; n = 20) served as a reference. The metabolic phenotype and liver lipid metabolism pathways were studied and compared by 1-way analysis of variance; P ≤ 0.05 was considered significant. RESULTS: NFM reduced body weight (BW) gain (46 ± 2.5 compared with 61 ± 3.5 %BW, P < 0.01) and hepatic triglyceride content (46.0 ± 10.4 compared with 71.7 ± 14.4 mg/g, P <0.05) compared with HFD. Immunoblotting revealed that NFM feeding increased hepatic mitochondrial complex abundance (P < 0.05) compared with WFM. Compared with NFM, WFM had higher triglyceride content (69.2 ± 16.5 compared with 46.0 ± 10.4 mg/g, P < 0.05) but reduced liver area covered by lipid droplets in comparison with HFD (6.49 ± 2.75 compared with 13.61 ± 2.75% standard area, P = 0.051). De novo lipogenesis enzymes, fatty acid synthase (1.33 ± 0.56 compared with 0.76 ± 0.56 AU, P < 0.05) and phosphorylated acetyl-CoA carboxylase (1.65 ± 0.49 compared with 0.02 ± 0.49 AU, P < 0.05) were increased compared with NFM. Carnitine palmitoyl transferase 1α (1.48 ± 0.19 compared with 1.00 ± 0.19 AU, P < 0.05) was increased in WFM compared with HFD animals, and Opa1 mRNA expression was increased in WFM (1.26 ± 0.21 compared with 0.66 ± 0.21 AU, P < 0.05) compared with the NFM group. CONCLUSIONS: Compared with WFM, NFM mice had greater benefits in mitigating MASLD progression through increased capacity for oxidative phosphorylation and fatty acid export, leading to reduced hepatic fat accumulation.