Antarctic Krill Euphausia superba Oil Supplementation Attenuates Hypercholesterolemia, Fatty Liver, and Oxidative Stress in Diet-Induced Obese Mice.

BACKGROUND: Several Previous studies indicate that consuming krill oil may aid in reducing hypercholesterolemia and improving cholesterol metabolism. Therefore, our study was designed to investigate the effectiveness of Antarctic krill oil (Euphausia superba) (ESKO) in combating obesity and lowering fat/lipid/cholesterol levels. METHODS: The study aimed to investigate the molecular docking model targeting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) using ESKO-derived eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and astaxanthin. In this study, histological alterations in the liver of the obesity model (ICR male mouse), obesity-related or antioxidant markers in both liver and serum, the molecular mechanisms in HepG2 cells and liver tissue, and HMGCR activity were analyzed. RESULTS: Our findings revealed that a high-fat diet (HFD) significantly led to increased oxidative stress, obesity-related indicators, and cardiovascular-associated risk indices. However, ESKO effectively mitigated HFD-induced oxidative stress, fat accumulation, and the suppression of low-density lipoprotein receptor (LDLR) or activation of related molecular pathways. This was achieved through improvements in metabolic parameters, including CD36/liver X receptor α (LXRα)/sterol regulatory element-binding protein 1c (SREBP1c), proprotein convertase subtilsin/kexin type 9 (PCSK-9), and HMGCR, ultimately ameliorating HFD-induced hypercholesterolemia and obesity. CONCLUSIONS: These beneficial findings indicate that ESKO might have significant potential for preventing and treating obesity-related disorders.