Comparative study on the effects of algal oil DHA calcium salt and DHA on lipid metabolism and oxidative stress in high-fat diet-induced mice

Hyperlipidemia, a metabolic disorder and a major risk factor for cardiovascular diseases such as atherosclerosis, is closely associated with lipid metabolism abnormalities. Algal oil-derived docosahexaenoic acid (DHA), rich in omega-3 (ω-3) fatty acids, has shown potential in improving lipid metabolism; however, its bioavailability remains limited. In this study, DHA was formulated as a calcium salt (DHA-Ca) to enhance its biological activity and was compared with conventional DHA in treating high-fat diet (HFD)-induced hyperlipidemia in mice. The results demonstrated that DHA-Ca was more effective than DHA in controlling body weight, modulating blood lipid profiles (lowering total cholesterol [TC] and low-density lipoprotein cholesterol [LDL-C] levels while increasing high-density lipoprotein cholesterol [HDL-C]), alleviating hepatic fat accumulation, and improving liver histopathology. Furthermore, DHA-Ca significantly reduced hepatic triglyceride (TG) and TC levels and enhanced antioxidant capacity by increasing glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) levels, and reducing malondialdehyde (MDA) content. Mechanistically, DHA-Ca more effectively activated the AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor alpha (PPARα)-carnitine palmitoyltransferase 1A (CPT1A)/acyl-CoA oxidase 1 (ACOX1) pathway and inhibited the AMPK-sterol regulatory element-binding protein 1c (SREBP1c)-acetyl-CoA carboxylase 1 (ACC1)/fatty acid synthase (FASN) pathway, thereby promoting fatty acid oxidation and suppressing lipid synthesis. In conclusion, DHA-Ca outperforms DHA in regulating lipid metabolism, preventing hepatic steatosis, and enhancing antioxidant defense, indicating its greater potential for therapeutic application.