n-3 polyunsaturated fatty acids in phospholipid or triacylglycerol form attenuate nonalcoholic fatty liver disease via mediating cannabinoid receptor 1/adiponectin/ceramide pathway.

n-3 polyunsaturated fatty acids (PUFA) have shown to exert beneficial effects in the treatment of nonalcoholic fatty liver disease (NAFLD). Supplements of n-3 PUFA occur in either phospholipid or triacylglycerol form. The present study aimed to compare whether the different n-3 PUFA of marine-origin, namely krill oil, DHA/EPA-phospholipid (PL), and EPA/DHA-triacylglycerol (TAG) forms had differential abilities to ameliorate NAFLD. The NAFLD model was established in mice fed a high-fat and high-cholesterol diet (HFD). The mice showed evidence of weight gain, dyslipidemia, insulin resistance and hepatic steatosis after 9 weeks of HFD, while the three forms of the n-3 PUFA reduced hepatic TAG accumulation, fatty liver and improved insulin instance, and hepatic biomarkers after 9 weeks of intervention. Of these, krill oil intervention significantly reduced adipocyte hypertrophy and hepatic steatosis in comparison with DHA/EPA-PL and EPA/DHA-TAG groups. Importantly, only krill oil intervention significantly reduced serum alanine transaminase, aspartate transaminase concentrations and low-density lipoprotein-cholesterol, compared with the HFD group. Supplemental n-3 PUFA lowered circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) concentrations, compared with the HFD group, which was associated with down-regulating CB1 and upregulating adiponectin expressions in adipose tissue. Besides, targeted lipidomic analyses indicated that the increased adiponectin levels were accompanied by reductions in hepatic ceramide levels. The reduced ceramide levels were associated with inhibiting lipid synthesis and increasing fatty acid β-oxidation, finally inhibiting TAG accumulation in the liver. Through mediating CB1/adiponectin/ceramide pathway, the present study suggested that administration of krill oil had superior health effects in the therapy of NAFLD in comparison with DHA/EPA-PL and EPA/DHA-TAG.

Chen YF ，Fan ZK ，Gao X ，Zhou F ，Guo XF ，Sinclair AJ ，Li D ... -  《-》

Diets enriched in menhaden fish oil, seal oil, or shark liver oil have distinct effects on the lipid and fatty-acid composition of guinea pig heart.

Murphy MG ，Wright V ，Ackman RG ，Horackova M ... -  《MOLECULAR AND CELLULAR BIOCHEMISTRY》

Accretion of Dietary Docosahexaenoic Acid in Mouse Tissues Did Not Differ between Its Purified Phospholipid and Triacylglycerol Forms.

Recent studies suggest that dietary krill oil leads to higher omega-3 polyunsaturated fatty acids (n-3 PUFA) tissue accretion compared to fish oil because the former is rich in n-3 PUFA esterified as phospholipids (PL), while n-3 PUFA in fish oil are primarily esterified as triacylglycerols (TAG). Tissue accretion of the same dietary concentrations of PL- and TAG-docosahexaenoic acid (22:6n-3) (DHA) has not been compared and was the focus of this study. Mice (n = 12/group) were fed either a control diet or one of six DHA (1%, 2%, or 4%) as PL-DHA or TAG-DHA diets for 4 weeks. Compared with the control, DHA concentration in liver, adipose tissue (AT), heart, and eye, but not brain, were significantly higher in mice consuming either PL- or TAG-DHA, but there was no difference in DHA concentration in all tissues between the PL- or TAG-DHA forms. Consumption of PL- and TAG-DHA at all concentrations significantly elevated eicosapentaenoic acid (20:5n-3) (EPA) in all tissues when compared with the control group, while docoshexapentaenoic acid (22:5n-6) (DPA) was significantly higher in all tissues except for the eye and heart. Both DHA forms lowered total omega-6 polyunsaturated fatty acids (n-6 PUFA) in all tissues and total monounsaturated fatty acids (MUFA) in the liver and AT; total saturated fatty acid (SFA) were lowered in the liver but elevated in the AT. An increase in the DHA dose, independent of DHA forms, significantly lowered n-6 PUFA and significantly elevated n-3 PUFA concentration in all tissues. Our results do not support the claim that the PL form of n-3 PUFA leads to higher n-3 PUFA tissue accretion than their TAG form.

Adkins Y ，Laugero KD ，Mackey B ，Kelley DS ... -  《-》

Metabolic effects of n-3 PUFA as phospholipids are superior to triglycerides in mice fed a high-fat diet: possible role of endocannabinoids.

Rossmeisl M ，Jilkova ZM ，Kuda O ，Jelenik T ，Medrikova D ，Stankova B ，Kristinsson B ，Haraldsson GG ，Svensen H ，Stoknes I ，Sjövall P ，Magnusson Y ，Balvers MG ，Verhoeckx KC ，Tvrzicka E ，Bryhn M ，Kopecky J ... -  《PLoS One》

Docosahexaenoic Acid Modulates Nonalcoholic Fatty Liver Disease by Suppressing Endocannabinoid System.

Endocannabinoid signaling regulates energy homeostasis, and is tightly associated with nonalcoholic fatty liver disease (NAFLD). The study previously finds that supplementation of docosahexaenoic acid (DHA) has superior function to ameliorate NAFLD compared with eicosapentaenoic acid (EPA), however, the underlying mechanism remains elusive. The present study aims to investigate whether DHA intervention alleviates NAFLD via endocannabinoid system. In a case-control study, the serum endocannabinoid ligands in 60 NAFLD and 60 healthy subjects are measured. Meanwhile, NAFLD model is established in mice fed a high-fat and -cholesterol diet (HFD) for 9 weeks. DHA or EPA is administrated for additional 9 weeks. Serum primary endocannabinoid ligands, namely anandamide (AEA) and 2-arachidoniylglycerol (2-AG), are significantly higher in individuals with NAFLD compared with healthy controls. NAFLD model shows that serum 2-AG concentrations and adipocyte cannabinoid receptor 1 expression levels are significantly lower in DHA group compared with HFD group. Lipidomic and targeted ceramide analyses further confirm that endocannabinoid signaling inhibition has exerted deletion of hepatic C16:0-ceramide contents, resulting in down-regulation of de novo fatty acid synthesis and up-regulation of fatty acid β-oxidation related protein expression levels. This work elucidates that DHA has improved NAFLD by suppressing endocannabinoid system.

Chen YF ，Fan ZK ，Wang YP ，Liu P ，Guo XF ，Li D ... -  《-》