Whey protein hydrolysate alleviated atherosclerosis and hepatic steatosis by regulating lipid metabolism in apoE-/- mice fed a Western diet

Whey protein hydrolysate (WPH) has been proved to possess various biological activities associated with the amelioration of cardiovascular disease (CVD). The objective of this study was to investigate the anti-atherosclerotic and hepatoprotective effects of WPH on apolipoprotein E knockout (apoE-/-) mice fed with a Western diet for 15 weeks. Results revealed that WPH markedly inhibited the development of atherosclerotic lesions in the aorta and steatosis injury in the liver. The serum lipid and inflammation levels were both reduced after WPH supplemented in apoE-/- mice. In addition, WPH inhibited the lipid accumulation in the liver, thereby decreasing the hepatic inflammation level and oxidative stress injury. Mechanism investigation revealed that WPH down-regulated the expression of cholesterol biosynthesis genes while up-regulated the expression of cholesterol uptake and excretion genes in the liver. Meanwhile, the de novo lipogenesis was inhibited while the fatty acids β-oxidation was activated in the liver by WPH supplementation. Notably, the n-3 polyunsaturated fatty acid (PUFA)/n-6 PUFA ratio in serum and liver of the WPH-H group were 2.69-fold (p < 0.01) and 3.64-fold (p < 0.01) higher than that of the Model group. Collectively, our results proved WPH possesses potent anti-atherosclerotic and hepatoprotective activities and has the potential to be used as a novel functional ingredient for the management of CVD.