Dietary n-3 PUFA as phospholipids

We have shown previously that a combination treatment using dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the form of triglycerides and thiazolidinedione (TZD) could efficiently prevent or reverse obesity and ameliorate insulin resistance in mice fed high-fat diet. Recent experiments have suggested that n-3 PUFA as phospholipids might be superior to triglycerides. Therefore, in this study, we investigated how n-3 PUFA as phospholipids, either alone or in combination with TZD, affect hepatic steatosis as well as lipid and glucose metabolism.

Diets: Adult male C57BL/6N mice were fed for 7 weeks a corn oil-based high-fat diet (cHF; lipids ˜35% wt/wt) or various cHF-based treatments: (i) PC, cHF with n-3 PUFA as phosphatidylcholine-rich concentrate; ii) R, cHF with 10mg rosiglitazone/kg diet; iii) PC+R. Chow-fed mice served as controls.

Results: Both PC and PC+R but not R prevented weight gain and improved glucose tolerance, while all treatments reduced the weight of abdominal fat and plasma levels of triacylglycerols and NEFA. Total plasma cholesterol was; however, lower only in the PC and PC+R groups. While R tended to increase hepatic lipids, both PC and PC+R treatments completely prevented the development of fatty liver. Furthermore, screening of hepatic gene expression showed a complex down-regulation of many biosynthetic pathways including lipogenesis as well as cholesterol and bile acid synthesis in the PC group. Conversely, fatty acid oxidation was stimulated, and the PC+R combination further potentiated this effect.

Conclusion: Dietary n-3 PUFA as phospholipids efficiently ameliorated obesity-associated metabolic defects such as dyslipidemia and glucose intolerance, while completely preventing the development of fatty liver. These effects were further potentiated when PC was combined with a low dose of TZD, suggesting its potential use in clinical settings.