Administration of Protein Hydrolysates from Anchovy (Engraulis Encrasicolus) Waste for Twelve Weeks Decreases Metabolic Dysfunction-Associated Fatty Liver Disease Severity in ApoE(–/–)Mice

SIMPLE SUMMARY: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasing concern worldwide. It currently represents the main cause of chronic liver disease in humans in Western countries. Nutritional strategies based on fish-rich diets are considered helpful in the prevention of MAFLD, and are also thought to be beneficial for human health. In particular, cholesterol- and triacylglycerol-lowering effects are associated with fish-derived proteins or hydrolysates. Our findings suggest that supplementing the diet with 10% (w/w) anchovy protein hydrolysates has an anti-obesity effect together with an improvement in lipid metabolism and a reduction in liver fat content and high-fat diet-induced liver disease. By virtue of their nutritional value and functional proprieties, anchovy by-product protein hydrolysates may be an efficient nutritional strategy in MAFLD prevention and treatment. ABSTRACT: Metabolic dysfunction-associated fatty liver disease (MAFLD) includes several diseases, ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Fish-rich diets are considered helpful in the prevention of MAFLD, and the enzymatic hydrolysis of fish waste has been explored as a means of obtaining high-value protein hydrolysates, which have been proven to exert beneficial bioactivities including anti-obesity and hypocholesterol effects. This study aimed to assess the effect of the administration of protein hydrolysates from anchovy waste (APH) for 12 weeks on attenuated high-fat diet-induced MAFLD in apolipoprotein E-knockout mice (ApoE(–/–)). Thirty ApoE(–/–) mice were divided into two groups (n = 15/group) and fed a high-fat diet (HFD), with and without the addition of 10% (w/w) APH. After 12 weeks, serum and hepatic lipid profiles, hepatic enzyme activities, liver histology and immunohistochemistry were analyzed to assess hepatic steatosis, inflammation and fibrosis. Twelve-weeks on a 10% (w/w) APH diet reduces total cholesterol and triglyceride serum levels, hepatic enzyme activity and hepatic triacylglycerol content (p < 0.0001), and results in a reduction in hepatic fat accumulation and macrophage recruitment (p < 0.0001). The results suggest that a 10% APH diet has an anti-obesity effect, with an improvement in lipid metabolism, hepatic steatosis and liver injury as a result of a high-fat diet. Protein hydrolysates from fish waste may represent an efficient nutritional strategy in several diseases, and their use as nutraceuticals is worthy of future investigation.