Nonfat milk supplementation mitigates hepatic lipid accumulation and improves hepatic lipid metabolism in an early metabolic dysfunction-associated steatotic liver disease (MASLD) C57BL/6N mouse model.

Abstract

Background: Dairy products may mitigate metabolic dysfunction-associated steatotic liver disease (MASLD) progression but the role of dairy fat is unclear.

Objective: This animal trial compares MASLD-related outcomes after feeding non- (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 (LFD) group (10% kcal fat; n=20) served as a reference. The metabolic phenotype and liver lipid metabolism pathways were studied and compared by one-way ANOVA; p ≤ 0.05 was considered significant.

Results: NFM reduced body weight (BW) gain (46±2.5 vs 61±3.5 %BW, p <0.01) and hepatic triglyceride (TG) content (46.0±10.4 vs 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 vs 46.0±10.4 mg/g, p < 0.05) but reduced liver area covered by lipid droplets in comparsion to HFD (6.49±2.75 vs 13.61±2.75 % standard area, p = 0.051). De novo lipogenesis enzymes, fatty acid synthase (1.33±0.56 vs 0.76±0.56 AU, p < 0.05) and phosphorylated acetyl-CoA carboxylase (1.65±0.49 vs 0.02±0.49 AU, p < 0.05) were increased compared with NFM. Carnitine palmitoyl transferase 1α (1.48±0.19 vs 1.00±0.19 AU, p < 0.05) was increased in WFM compared to HFD animals and Opa1 mRNA expression was increased in WFM (1.26±0.21 vs 0.66±0.21 AU, p < 0.05) versus the NFM group.

Conclusions: Compared with WFM, NFM mice had greater benefits on mitigating MASLD progression through increased capacity for oxidative phosphorylation and fatty acid export, leading to reduced hepatic fat accumulation.