Differential effects of milk, yogurt, and cheese on energy homeostasis and brown adipose tissue phenotype in high-fat diet-induced obese mice†

Aim: We hypothesized that milk, yogurt, and cheese have differential impacts on energy expenditure (EE) and obesity in mice fed a high-fat diet (HFD). Methods: C57BL/6 mice (n = 16 per group) were fed a HFD or a HFD supplemented with fat-free milk (MILK), fat-free plain yogurt (YOG), or reduced-fat cheddar cheese (CHE; 19 kcal% fat), each provided at 10% of the daily energy intake, for 8 weeks. EE was quantified using a metabolic chamber. Metabolic pathways related to BAT mitochondrial function and uncoupling protein 1 (UCP1) abundance were assessed. Serum lipidomic profiles were analyzed to identify potential mediators of the observed effects. Results: MILK supplementation lowered weight gain and fat accumulation and enhanced EE and BAT thermogenesis, perhaps via the SIRT1-AMPK-PGC1α axis in BAT. This led to elevated UCP1 abundance and enhanced the abundance of hormone-sensitive lipase (HSL). MILK also altered serum lipid species, indicating enhanced energy use, and promoted BAT thermogenesis and mitochondrial function pathways. YOG exhibited a similar pattern but a lower magnitude of effects than MILK on reducing weight gain and fat mass, increasing EE, and BAT thermogenic proteins, including AMPK-PGC1α-UCP1. Both MILK and YOG showed a relative increase in serum PC 15:0_15:0 and LPC 15:0. In contrast, CHE reduced weight gain and increased EE without impacting BAT thermogenesis proteins or serum lipid species. Conclusion: Our study showed that MILK, YOG, and CHE reduced weight gain in mice on a HFD by increasing EE. MILK and YOG also up-regulated BAT thermogenesis, while both additionally altered lipids involved in fat metabolism and inflammation. CHE did not affect BAT thermogenesis and lipid species compared to HFD.