摘要
This study aimed to compare the dose-and formulation-dependent effects of fish oil on metabolic disorders in high-fat diet(HFD)-fed mice.HFD significantly increased body weight and hepatic fat accumulation,elevated serum triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C),suppressed antioxidant enzyme activities(SOD,CAT),exacerbated inflammation,and reduced gut microbialα-diversity along with an increased Firmicutes/Bacteroidota ratio.Fish oil supplementation exerted dose-dependent im-provements:high-dose fish oil more effectively downregulated lipid droplet-associated proteins(Scd1,Plin2)and upregulated antioxidative markers(Idh1,Gstp2),resulting in improved lipid profiles,oxidative status,and in-flammatory markers compared to low-dose fish oil.Notably,fish oil emulsions exhibited superior efficacy.In particular,the high-dose fish oil emulsion(HFE)group showed the greatest reductions in TG,TC,and LDL-C,restoration of SOD and CAT activities,and marked shrinkage of hepatic lipid droplets.Data-independent acquisition-based proteomic analyses revealed that HFE treatment regulated key metabolic pathways,including PPAR signaling,peroxisome function,and cholesterol metabolism.Additionally,HFE increased beneficial genera(e.g.,Muribaculaceae)and reduced pathogenic genera(e.g.,Helicobacter,Faecalibaculum).In conclusion,high-dose fish oil emulsion demonstrated the strongest efficacy in promoting hepatic lipid meta-bolism,alleviating inflammation and oxidative stress,and restoring gut microbial diversity,highlighting its potential as a targeted nutritional intervention to combat diet-induced metabolic disorders and support precision functional food development.
基金
supported by the National Natural Science Foundation of China(No.32272473,32402296&32302287)
Natural Science Foundation of Zhejiang Province(No.LR23C200003,LR24C200001&LQN25C200007)
Zhejiang Provincial Key Research and Development Program(No.2025C04042&2025C01101)
National Key R&D Program of China(No.2024YFF1105605)
Enterprise Joint Project(Zhejiang University of Technology grant No.KYYZH2024013).
