Cow's milk increases the activities of human nuclear receptors peroxisome proliferator-activated receptors α and δ and retinoid X receptor α involved in the regulation of energy homeostasis, obesity, and inflammation

Selectivity of the agonistic activity of milk. The agonistic effect of cow's milk on peroxisome proliferator-activated receptor (PPAR) subtypes was evaluated by conducting reporter gene assays using PPAR agonists WY14643, GW501516, and pioglitizone (PGZ) as positive controls for PPARα, PPARδ, and PPARγ, respectively. Details are described in the text. All values are means ± SD for 3 tests. *P<0.5; **P<0.01; ***P<0.001 compared with controls (distilled water 0.5%).

Selectivity of the agonistic activity of various dairy products. The agonistic effects of ice cream, butter, yogurt, and vegetable cream were determined as described in Figure 1. All values are means±SD for 3 tests. *P<0.5; **P<0.01; ***P<0.001 compared with controls (distilled water 0.5%). WY14643, GW501516, and pioglitizone (PGZ) are peroxisome proliferator-activated receptor (PPAR) agonists.

Effect of defatting on the agonistic activity of milk. The agonistic effects of milk and skim milk were determined as described in Figure 1. All values are means±SD for 3 tests. **P<0.01; ***P<0.001 compared with controls (distilled water 0.5%). WY14643, GW501516, and pioglitizone (PGZ) are peroxisome proliferator-activated receptor (PPAR) agonists.

Effect of milk and fresh cream on the activities of various nuclear receptors. The agonistic effect of milk and fresh cream on peroxisome proliferator-activated receptor (PPAR) α, δ, γ, vitamin D3 receptor (VDR), estrogen receptors (ER) α and β, thyroid receptors (TR) α and β, and retinoid X receptor (RXR) α were determined as described in the text using 1α,25-dihydroxy-vitamin D3 as a positive control for VDR, β-estradiol for ERα and ERβ, 3,3′,5′-triiodo-l-thyronine (T3) for TRα and TRβ, and 9-cis-retinoic acid (9cRA) for RXRα. All values are means±SD for 3 tests. **P<0.01; ***P<0.001 compared with controls (distilled water 0.5%). WY14643, GW501516, and pioglitizone (PGZ) are peroxisome proliferator-activated receptor (PPAR) agonists.

Effect of milk and fresh cream on the expression of uncoupling protein 2 (UCP2). The effect of milk and fresh cream on the expression of UCP2 in L6 cells was determined by real-time PCR. All values are means±SD for 3 tests. **P<0.01; ***P<0.001 compared with controls (distilled water 0.5%). GW501516 is a peroxisome proliferator-activated receptor (PPAR)δ agonist.

Effect of short interfering (si)RNA on the expression of uncoupling protein 2 (UCP2). The effect of control siRNA and peroxisome proliferator-activated receptor (PPAR)δ-siRNA on the expression of UCP2 in L6 cells was determined as described in the text. All values are means ± SD for 3 tests. *P<0.5, ***P<0.001 compared with respective control siRNA. GW501516 is a peroxisome PPAR agonist.