Fish Oil Alters the Metabolome, Antioxidative Potential, and Secretory Profile of Visceral Adipose Tissue in Mice with High-Fat Diet-Induced Obesity Compared with Other Dietary Fat Sources

Dietary fat quality, determined by fatty acid composition, plays a central role in regulating adipose tissue function and metabolic homeostasis in obesity. This study examined whether different dietary fat sources modulate the secretory activity, antioxidant capacity, and metabolomic profiles of visceral adipose tissue (VAT) in mice with established high-fat diet (HFD)-induced obesity. Male C57BL/6J mice were rendered obese by long-term feeding with a lard-based HFD and subsequently maintained on isocaloric HFDs containing lard, coconut oil, olive oil, or fish oil. Antioxidant capacity, redox enzyme activities, adipokine levels, and untargeted metabolomic profiles of VAT were analyzed. Fish oil-enriched HFD significantly improved antioxidant potential and partially restored redox enzyme activity compared with the lard-based diet. It preserved adiponectin levels and reduced leptin accumulation in VAT. Multivariate metabolomic analyses showed clear separation of dietary groups and distinct metabolic signatures related to fat quality. Replacement of lard with fish oil induced a coordinated remodeling of the lipid and amino acid metabolism and reduced metabolites linked to mitochondrial overload and oxidative stress, whereas saturated fat-rich diets promoted patterns consistent with metabolic dysfunction. These findings indicate that dietary fat quality reshapes adipose tissue metabolism in obesity and highlights fish oil as a strategy to attenuate adipose tissue dysfunction.