Differential Effects of Milk, Yogurt, and Cheese on Energy Homeostasis and Brown Adipose Tissue Phenotype in High-Fat Diet-Induced Obese Mice

Abstract

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 an HFD or HFD supplemented with fat-free milk (MILK), fat-free plain yogurt (YOG), or reduced-fat cheese (CHE; 19 kcal% fat), each provided at 10% of the daily energy intake, for 8 weeks. EE and respiratory quotient (RQ) were quantified using a metabolic chamber. Metabolic pathways related to BAT mitochondrial function and uncoupling protein 1 (UCP1) abundance were assessed. Serum lipidomics profiles were analyzed to identify potential mediators of the observed effects. Results: MILK supplementation resulted in reduced weight gain and fat mass, alongside increased EE, and BAT thermogenesis, at least in part mediated by the SIRT1-PPARγ–PGC1α axis in BAT to increase UCP1 abundance and increase the abundance of Hormone-sensitive lipase (HSL). MILK also increased the abundance of serum lipid species, which shifted by aligning with improved energy utilization and induced pathways involved with thermogenesis and mitochondrial function in BAT. YOG exhibited a similar pattern but fewer effects than MILK in reducing weight gain and fat mass increment, increasing EE, and BAT thermogenic proteins. YOG also decreased serum lipid species related to inflammation and oxidative stress. In contrast, CHE decreased weight gain and increased EE without affecting the proteins of BAT, with a similar pattern of serum lipid species to HFD. Conclusion: Our study shows that the supplementation of MILK, YOG, and CHE reduces the weight of HFD-fed mice by increasing the EE, which only MILK accomplishes by upregulating BAT thermogenesis. YOG also exerts beneficial effects on the BAT lipidome. CHE does not affect BAT thermogenesis.