Astaxanthin Ameliorates Skeletal Muscle Atrophy in Mice With Cancer Cachexia.

Astaxanthin (AST) is a natural marine carotenoid with a variety of biological activities. This study aimed to demonstrate the possible mechanisms by which AST improves skeletal muscle atrophy in cancer cachexia. In this study, the effects of different doses of AST (30 mg/kg b.w., 60 mg/kg b.w. and 120 mg/kg b.w.) on skeletal muscle functions were explored in mice with cancer cachexia. The results showed that AST (30, 60 and 120 mg/kg b.w.) could effectively protect cachexia mice from body weight and skeletal muscle loss. AST dose-dependently ameliorated the decrease in myofibres cross-sectional area and increased the expression of myosin heavy chain (MHC). AST treatment decreased both the serum and muscle level of IL-6 but not TNF-α in C26 tumor-bearing cachexia mice. Moreover, AST alleviated skeletal muscle atrophy by decreasing the expression of two muscle-specific E3 ligases MAFBx and MuRF-1. AST improved mitochondrial function by downregulating the levels of muscle Fis1, LC3B and Bax, upregulating the levels of muscle Mfn2 and Bcl-2. In conclusion, our study show that AST might be expected to be a nutritional supplement for cancer cachexia patients.

Astaxanthin exerts an adjunctive anti-cancer effect through the modulation of gut microbiota and mucosal immunity.

This study aimed to investigate the function of gut microbiota in astaxanthin's adjuvant anticancer effects. Our prior research demonstrated that astaxanthin enhanced the antitumor effects of sorafenib by enhancing the body's antitumor immune response; astaxanthin also regulated the intestinal flora composition of tumor-bearing mice. However, it is presently unknown whether this beneficial effect is dependent on the gut microbiota. We first used broad-spectrum antibiotics to eradicate gut microbiota of tumor-bearing mice, followed by the transplantation of fecal microbiota. The results of this study indicate that the beneficial effects of astaxanthin when combined with molecular targeting are dependent on the presence of intestinal microbiota. Astaxanthin facilitates the infiltration of CD8+ T lymphocytes into the tumor microenvironment and increases Granzyme B production by modulating the intestinal flora. Therefore, it strengthens the body's anti-tumor immune response and synergistically boosts the therapeutic efficacy of drugs. Astaxanthin stimulates the production of cuprocytes and mucus in the intestines by promoting the proliferation of Akkermansia. In addition, astaxanthin enhances the intestinal mucosal immunological function. Our research supports the unique ability of astaxanthin to sustain intestinal flora homeostasis and its function as a dietary immune booster for individuals with tumors.

Astaxanthin Augmented the Anti-Hepatocellular Carcinoma Efficacy of Sorafenib Through the Inhibition of the JAK2/STAT3 Signaling Pathway and Mitigation of Hypoxia within the Tumor Microenvironment.

SCOPE: The optimization of anti-cancer drug effectiveness through dietary modifications has garnered significant attention among researchers in recent times. Astaxanthin (AST) has been identified as a safe and biologically active dietary supplement. METHODS AND RESULTS: The tumor-bearing mice are treated with sorafenib, along with supplementation of 60 mg kg-1 AST during the treatment. The coadministration of AST and a subclinical dosage of 10 mg kg-1 sorafenib demonstrates a tumor inhibition rate of 76.5%, which is notably superior to the 45% inhibition rate observed with the clinical dosage of 30 mg kg-1 sorafenib (p < 0.05). The administration of AST leads to a tumor inhibition increase of around 25% when combined with the clinical dose of 30 mg kg-1 sorafenib (p <0.05). AST enhances the inhibitory effect of sorafenib on tumor angiogenesis through the JAK2/STAT3 signaling pathway. Furthermore, AST exhibits a reduction in hypoxia within the tumor microenvironment. CONCLUSION: The results suggest that AST supplement enhances the inhibitory effects of sorafenib on hepatocellular carcinoma. This study presents a new dietary management program for oncology patients.

Astaxanthin slows down skeletal muscle atrophy in H22 tumor-bearing mice during sorafenib treatment by modulating the gut microbiota.

Astaxanthin is a carotenoid that is taken orally and has antitumor and anti-inflammatory properties. Our previous research demonstrated that astaxanthin alleviated skeletal muscle atrophy during sorafenib treatment in H22 tumor-bearing mice and altered the intestinal flora composition. However, the relationship between astaxanthin's amelioration of skeletal muscle atrophy in tumor-bearing mice and its ability to regulate intestinal flora is not clear. We used broad-spectrum antibiotics to create pseudo-sterile tumor-bearing mice, which we then used in fecal bacteria transplantation experiments. Our results indicate that the role of astaxanthin in ameliorating skeletal muscle atrophy during molecularly targeted therapy in mice with tumors is dependent on the intestinal flora. Astaxanthin substantially promoted the proliferation of Blautia, Parabacteroides, and Roseburia, altered the levels of metabolites in mouse serum, and primarily affected the amino acid metabolism of mice. Astaxanthin ameliorated skeletal muscle atrophy by promoting the activation of AKT/FOXO3a, which inhibited the expression of ubiquitination-degrading Fbx32 and MuRF1 and promoted myogenesis in skeletal muscle. Our study confirms that the intestinal flora is an important target for astaxanthin to combat skeletal muscle atrophy. Our research supports the use of astaxanthin as a nutritional supplement and intestinal microecological regulator for cancer patients.

Dietary supplementation with astaxanthin enhances anti-tumor immune response and aids the enhancement of molecularly targeted therapy for hepatocellular carcinoma.

Astaxanthin is a naturally occurring compound that possesses immunomodulatory properties. The results of our previous investigation indicated that astaxanthin has the potential to augment the anticancer effectiveness of the targeted medication sorafenib. However, the precise molecular mechanism underlying this phenomenon remains unclear. H22 tumor-bearing mice were treated with sorafenib at 30 mg kg-1 per day and their diet was supplemented with 60 mg kg-1 day-1 astaxanthin orally for a period of 18 days. The study revealed that the addition of astaxanthin to the diet facilitated the transition of tumor-associated macrophages from the M2 phenotype to the M1 phenotype. The application of astaxanthin resulted in an augmentation of CD8+ T cell infiltration within the tumor microenvironment through the activation of the CXCL9/CXCR3 signaling axis. Astaxanthin was found to enhance the production of cytokines that possess antitumor properties, including Granzyme B. Furthermore, the administration of astaxanthin resulted in alterations to the intestinal microbiota in H22-bearing mice, leading to the growth of bacteria that possess anti-tumor immune properties, such as Akkermansia. The findings of these studies indicate that astaxanthin has the potential to augment the immune response against tumors when used in conjunction with sorafenib. These studies offer a novel framework for the advancement of astaxanthin as an immunomodulatory agent and a dietary supplement for individuals with tumors.

Astaxanthin Supplementation Assists Sorafenib in Slowing Skeletal Muscle Atrophy in H22 Tumor-Bearing Mice via Reversing Abnormal Glucose Metabolism.

SCOPE: Cachexia, which is often marked by skeletal muscular atrophy, is one of the leading causes of death in cancer patients. Astaxanthin, a carotenoid obtained from marine organisms that can aid in the prevention and treatment of a variety of disorders. In this study, to assess whether astaxanthin ameliorates weight loss and skeletal muscle atrophy in sorafenib-treated hepatocellular carcinoma mice is aimed. METHODS AND RESULTS: H22 mice are treated with 30 mg kg-1  day-1 of sorafenib and 60 mg kg-1  day-1 of astaxanthin by gavage lasted for 18 days. Sorafenib does not delay skeletal muscle atrophy and weight loss, although it does not reduce tumor burden. Astaxanthin dramatically delays weight loss and skeletal muscle atrophy in sorafenib-treating mice, without affecting the food intake. Astaxanthin inhibits the tumor glycolysis, slows down gluconeogenesis, and improves insulin resistance in tumor-bearing mice. Astaxanthin increases glucose competition in skeletal muscle by targeting the PI3K/Akt/GLUT4 signaling pathway, and enhances glucose utilization efficiency in skeletal muscle, thereby slowing skeletal muscle atrophy. CONCLUSION: The findings show the significant potential of astaxanthin as nutritional supplements for cancer patients, as well as the notion that nutritional interventions should be implemented at the initiation of cancer treatment, as instead of waiting until cachexia sets in.

Colon and gut microbiota greatly affect the absorption and utilization of astaxanthin derived from Haematococcus pluvialis.

Astaxanthin has been widely favored as a health food supplement by individuals but its absorption in the body seems not to be satisfactory. In addition, the peak time of astaxanthin derived from Haematococcus pluvialis in the plasma was much longer than other carotenoids found in our previous research. Thus, it is necessary to explore the process that affects the absorption of astaxanthin in order to potentially find a novel approach to improve the absorption in the future. In this study, we confirmed that the colon has an ability to absorb astaxanthin and conducted acute feeding experiments with the treatment of antibiotics in C57BL/6J mice and chronic feeding experiments in germ-free (GF) mice to detect the relationship between the gut microbiota and the absorption of astaxanthin. Our study showed that the decrease of gut microbiota led to a less oral absorbability, which might be related to the decreased expression of SR-BI in the small intestine and the reduction of free form and Z-astaxanthin converted by the gut microbiota found in the vitro culture. The experiments of anaerobic culture also implied that Lactobacillus might play an important role in the absorption of astaxanthin.

Kappaphycus Alvarezii Compound Powder Prevents Chemotherapy-Induced Intestinal Mucositis in BALB/c Mice.

This study aimed to formulate Kappaphycus alvarezii compound powder containing Kappaphycus alvarezii powder (KP), cooked sorghum powder (SP), and longan powder (LP); which was evaluated for its therapeutic effects against chemotherapy-induced intestinal mucosal injury (CIMI). Based on rheological properties, sensory evaluation, and antioxidant activity and using single factor and response surface methodology, the optimal formula to develop the compound powder was determined to be 35% KP, 30% SP, 5% LP, and 30% xylitol. Thereafter, the efficacy of the compound powder was tested by feeding BALB/c mice with diets supplemented with the Kappaphycus alvarezii compound powder (3% and 5%) for 14 consecutive days. The chemotherapeutic drug 5-fluorouracil was intraperitoneally injected (50 mg/kg) in the mice to induce CIMI for the last three consecutive days. Compared to the CIMI mice, those fed 5% Kappaphycus alvarezii compound powder (HC) showed significantly improved the intestinal injury, increased mucin-2 secretion, and reduced TNF-α, IL-1ß, IL-6, LT, and COX-2 levels. Furthermore, HC intake significantly reduced the Firmicutes-to-Bacteroidetes ratio, promoted the growth of beneficial bacteria, such as Alloprevotella, and inhibited the growth of harmful bacteria, such as Clostridium. In conclusion, HC has a protective effect against CIMI and provides a novel dietary strategy for patients undergoing chemotherapy.

Triacylglycerol rich in docosahexaenoic acid regulated appetite via the mediation of leptin and intestinal epithelial functions in high-fat, high-sugar diet-fed mice.

High-fat, high-sugar diet (HFHS) induced leptin resistance and intestinal epithelial dysfunction is implicated in hyperphagia and metabolic disorders. Numerous studies have demonstrated the efficacy of dietary interventions for reducing appetite. This study aims to investigate whether triacylglycerol rich in DHA (DHA-TG) could regulate appetite in mice fed with a HFHS diet and the mechanism by which it achieves that. DHA-TG could reduce food intake and regulate neuropeptides (POMC, AgRP, and NPY) expression in HFHS diet-fed mice. Hypothalamic transcriptome analysis reveals that these effects might be attributed to the role of DHA-TG in modulating hormone secretion and digestive system process. According to ELISA and RT-qPCR analysis, DHA-TG ameliorated leptin secretion and attenuated central leptin resistance induced by HFHS diet feeding. Besides, DHA-TG prevented the damage of intestinal epithelial barrier in nutritive obese mice by improving leptin sensitivity. Based on jejunal transcriptome analysis, DHA-TG also protected intestinal endocrine function, especially the secretion of another anorectic hormone, cholecystokinin (CCK), in HFHS diet-fed mice. Furthermore, DHA-TG was ineffective in repressing appetite, and improving gut leakage in leptin-deficient mice (ob/ob mice). In conclusion, DHA-TG has a potential to regulate appetite with the action of leptin, and intestinal epithelial functions in HFHS diet-fed mice.

Sun-Dried and Air-Dried Kappaphycus alvarezii Attenuates 5-Fluorouracil-Induced Intestinal Mucositis in Mice.

5-fluorouracil (5-FU)-induced intestinal mucositis (IM) often makes chemotherapy patients suffer from physical and psychological suffering. Kappaphycus alvarezii (KA) is known for its potent multiple biological activities from decades. In the current study, we explored the effect of sun-dried and air-dried Kappaphycus alvarezii as a whole food supplement on 5-FU-induced IM. Diets supplemented with sun-dried Kappaphycus alvarezii (SKA, 3%), air-dried Kappaphycus alvarezii (AKA, 3%), and 5-aminosalicylic acid (0.005%) for consecutive14 days. While intraperitoneal injection of 5-FU (50 mg/kg) induced IM for last three consecutive days, and IM was assessed by the disease activity index (DAI) and inflammatory cytokine levels. Pretreatment of KA could alleviate phenotypic index, inhibit the increase of DAI, and reverse villus/crypt ratio. On the 14th day, AKA significantly increased the weight growth rate of the mice. The intervention of SKA significantly reduced the level of TNF-α and IL-1ß (P < 0.01, P < 0.01), while the intervention of AKA significantly inhibited the level of TNF-α, IL-1ß, and LT (P < 0.01, P < 0.01, P < 0.001). Therefore, these results showed that KA as a whole food supplement might be prevent the 5-FU-induced IM. For the first time suggest that the use of AKA might be more effective than SKA despite exact mechanism still needs further study.

Effects of curcumin-mediated photodynamic treatment on lipid degradation of oysters during refrigerated storage.

BACKGROUND: Oyster's lipid degradation leads to a decrease in edible and nutritional value. Curcumin-mediated photodynamic treatment (PDT) is an innovative non-thermal technology, although evaluation of the oyster's lipid degradation has been scarce. In the present study, we investigated peroxide value, thiobarbituric acid reactive substance, triacylglycerol and free fatty acids to evaluate the effect of curcumin-mediated PDT on lipid degradation of oysters during refrigerated storage. RESULTS: The results showed that curcumin-mediated PDT could delay oyster's lipid degradation. Next, the activities of enzymes were detected to determine the mechanisms behind the effects of curcumin-mediated PDT. It was revealed that the activities of lipase, phospholipase A2 (PLA2 ), phospholipase C (PLC), phospholipase D (PLD) and lipoxygenase (LOX) were significantly inhibited after curcumin-mediated PDT (P < 0.05). Furthermore, 16 s rRNA analysis established that the relative abundances of Pseudoalteromonas and Psychrilyobacter were reduced by 51.58% and 43.82%, respectively, after curcumin-mediated PDT. CONCLUSION: Curcumin-mediated PDT could delay oyster's lipid degradation by inhibiting the activities of lipase, PLA2 , PLC, PLD and LOX, as well as by changing the oyster's microbial composition, reducing the relative abundance of Pseudoalteromonas and Psychrilyobacter. © 2021 Society of Chemical Industry.

Drug-guided screening for pancreatic lipase inhibitors in functional foods.

Chronic diseases, such as obesity, cause great harm to human health. Conventional drugs have promising therapeutic effects but also cause significant side effects. Functional foods are an excellent therapeutic alternative to pharmaceuticals, as they have fewer side effects. However, screening for active ingredients in natural foods is difficult. In this study, a novel pancreatic lipase inhibitor screening strategy, guided by the drug molecule orlistat, was combined with experimental verification. Twenty compounds from natural foods were evaluated based on the characteristics of orlistat interaction with pancreatic lipase. The characteristics of 13 molecules were comparable to those of orlistat. The pancreatic lipase inhibition rates of curcumin and sinensetin were 82.42 ± 0.50% and 81.07 ± 2.05%, respectively, and their IC50 values were 0.971 mM and 0.526 mM, respectively; both the inhibition rates as well as IC50 values were similar to those of orlistat. Curcumin and sinensetin prevented weight gain in mice by 69.17% and 52.29%, respectively, compared to orlistat. Curcumin and sinensetin did not cause significant organ damage in vivo, but significantly reduced the contents of triglycerides and cholesterol in blood and lipids in the liver, protecting liver function. Furthermore, 57 328 molecules in the Chinese Natural Product Database library were screened, and 20 potentially active molecules, found to be highly efficient in our study, were selected. Thus, we successfully established an efficient and accurate strategy for screening active ingredients in natural foods under the guidance of a drug molecule, providing valuable insights for functional food development.

Sargassum fusiforme together with turmeric extract and pomegranate peel extract alleviates obesity in high fat-fed C57BL/6J mice.

Sargassum fusiforme, a nutritious edible brown alga, has been widely suggested to play an important role in the development of functional food because of its multiple biological activities. The aim of this study was to explore the anti-obesity effect of the combination of Sargassum fusiforme with extracts of fruit and vegetable by comparing the effects of Sargassum fusiforme (S), Sargassum fusiforme together with pomegranate peel extract (SP), Sargassum fusiforme together with turmeric extract (ST) and Sargassum fusiforme together with turmeric extract and pomegranate peel extract (C) on diet-induced obese C57BL/6J mice. Long-term consumption of a high-fat diet can lead to high levels of blood lipid, increase adipocyte size, and cause lipid metabolism dysfunction and gut microbiota dysbiosis. According to the results of the experiments, SP and ST were more effective in reducing lipid levels and fat accumulation than S; and, C exhibited the strongest efficacy compared with the other three supplements. ST and C also regulated adipocytokines and had significant effects on the gene expression of lipid metabolism. We also found that C alleviated the imbalance of intestinal flora caused by a high-fat diet to a certain extent. In conclusion, SP, ST and C have anti-obesity potentials, which can be used as alternative ingredients in the formula of functional food for obese people.

Absorbability of Astaxanthin Was Much Lower in Obese Mice Than in Normal Mice.

Astaxanthin has been favored as a health food supplement by obese consumers. However, no detailed descriptions are available concerning the absorption of astaxanthin in obese individuals. In this study, we conducted acute and chronic feeding experiments in C57BL/6J mice to study the differences in astaxanthin absorption in normal and obese bodies. The obesity condition greatly decreased astaxanthin concentration in the blood and liver, its accumulation in tissues and organs, and the bioaccessibility. This may be related to the excessive intake of sucrose, fatty acids, and cholesterol, the increased gastrointestinal motility, and the disorder of gut microbiota in the obese body. Overall, our study showed that the obese body had a far less oral absorbability of astaxanthin than a normal body, and we suggest that the recommended or approved doses of astaxanthin can be properly increased for the obese body in the hope that astaxanthin will play a more active role in obese individuals.

Molecular and Microbial Signatures Predictive of Prebiotic Action of Neoagarotetraose in a Dextran Sulfate Sodium-Induced Murine Colitis Model.

Neoagarotetraose (NT), a hydrolytic product of agar by ß-agarase, is known to possess bioactive properties. However, the mechanisms via which NT alleviates intestinal inflammation remain unknown. In this study, a dextran sulfate sodium (DSS)-induced murine model was developed to evaluate the effect of NT on gut microbiome and microbial metabolism using 16S rRNA gene sequencing and untargeted metabolomics. Our data demonstrate that NT ingestion improved gut integrity and inflammation scores. NT reversed the abundance of Proteobacteria from an elevated level induced by DSS and significantly increased the abundance of Verrucomicrobia. Further, NT significantly increased the abundance of Akkermansia and Lactobacillus and concomitantly decreased that of Sutterella, which were among the important features identified by random forests analysis contributing to classification accuracy for NT supplementation. A microbial signature consisting of Adlercreutzia (denominator) and Turicibacter (numerator) predicted the NT supplementation status. Moreover, NT significantly modulated multiple gut metabolites, particularly those related to histidine, polyamine and tocopherol metabolism. Together, our findings provided novel insights into the mechanisms by which NT modulated the gut microbiome and metabolome and should facilitate the development of NT as a potent prebiotic for colitis management.

Inactivation of microbes on fruit surfaces using photodynamic therapy and its influence on the postharvest shelf-life of fruits.

In this study, the disinfection effect of curcumin-mediated photodynamic therapy on the contact surfaces of fresh fruit was investigated. Our results showed that the optimum concentration of curcumin and the energy density required were 0.5 µM and 7.2 J/cm2, respectively. Photodynamic therapy showed an excellent disinfection rate for the fresh fruits with a reduction of more than 80% in the total bacteria and coliform counts. The photodynamic therapy inhibited species that belonged to the categories of gram-negative and facultative anaerobic bacteria, except for two species of the Trichoderma fungus. Importantly, photodynamic therapy prolonged the shelf-life of grapes for two days at room temperature. Therefore, photodynamic therapy should be commercialized as a high efficiency and non-thermal sterilization technology for use in the food industry.

Malvidin 3-Glucoside Modulated Gut Microbial Dysbiosis and Global Metabolome Disrupted in a Murine Colitis Model Induced by Dextran Sulfate Sodium.

SCOPE: This study aims to elucidate the mechanisms of the anthocyanin malvidin 3-glucoside (MV) in alleviating gut dysbiosis using a murine colitis model induced by dextran sulfate sodium (DSS). METHODS AND RESULTS: The effect of MV on the structure and function of the colon microbiome and microbial metabolism is evaluated using 16S rRNA gene sequencing, global metabolomics, and a network algorithm based on the random-matrix theory. MV ingestion improved histopathological scores and increased IL10 expression in the colon mucosa of colitis mice. While DSS has a profound effect on the gut microbiome and significantly decreases both microbial richness and evenness, MV further reduces evenness but promotes microbial interactions and restores the Firmicutes/Bacteroidetes ratio repressed by DSS. Moreover, MV reduces the abundance of pathogenic bacteria, such as Ruminococcus gnavus, in colitis mice and has a strong modulatory effect on microbial co-occurrence patterns and gut metabolites. In addition, MV reverses several key inflammatory mediators, including sphingolipid metabolites, from elevated levels in DSS colitis mice. As a bioactive ingredient, MV exerts its effect on the gut microbiome in a mechanism that differs from the whole blueberry. CONCLUSION: MV ingestion ameliorates intestinal inflammation by modulating colon epithelium integrity, gut microbiome, and key inflammatory mediators.

Microbial Co-Occurrence Patterns and Keystone Species in the Gut Microbial Community of Mice in Response to Stress and Chondroitin Sulfate Disaccharide.

Detecting microbial interactions is essential to the understanding of the structure and function of the gut microbiome. In this study, microbial co-occurrence patterns were inferred using a random matrix theory based approach in the gut microbiome of mice in response to chondroitin sulfate disaccharide (CSD) under healthy and stressed conditions. The exercise stress disrupted the network composition and microbial co-occurrence patterns. Thirty-four Operational Taxonomic Units (OTU) were identified as module hubs and connectors, likely acting as generalists in the microbial community. Mucispirillum schaedleri acted as a connector in the stressed network in response to CSD supplement and may play a key role in bridging intimate interactions between the host and its microbiome. Several modules correlated with physiological parameters were detected. For example, Modules M02 (under stress) and S05 (stress + CSD) were strongly correlated with blood urea nitrogen levels (r = 0.90 and -0.75, respectively). A positive correlation between node connectivity of the OTUs assigned to Proteobacteria with superoxide dismutase activities under stress (r = 0.57, p < 0.05) provided further evidence that Proteobacteria can be developed as a potential pathological marker. Our findings provided novel insights into gut microbial interactions and may facilitate future endeavor in microbial community engineering.

Effects of curcumin-based photodynamic treatment on the storage quality of fresh-cut apples.

Photodynamic treatment (PDT) is an innovative technology with non-thermal and environmentally sound merits, but the evaluation on the storage qualities of fresh produce was scarce. In this study, the effects of curcumin-based PDT on the quality of fresh-cut 'Fuji' apple slices during storage at 4 °C were investigated. The impacts on the survival of Escherichia coli, color and weight loss were examined under different curcumin concentrations, illumination time or incubation time. Curcumin-based photodynamic inactivation of E. coli on the surface of apple slices reached 0.95 log. Curcumin-based PDT was proven to prevent browning and weight loss. Additionally, PDT significantly reduced the activity of polyphenol oxidase and peroxidases to 48% and 51%, respectively. Moreover, there were few negative changes in total phenolic, ascorbic acid content and anti-oxidant activity of the treated apples. These results indicated that curcumin-based PDT was a viable and promising non-thermal technology to preserve the quality of fresh produce.

Comparative Analysis of EPA/DHA-PL Forage and Liposomes in Orotic Acid-Induced Nonalcoholic Fatty Liver Rats and Their Related Mechanisms.

Nonalcoholic fatty liver disease (NAFLD) has become one predictive factor of death from various illnesses. The present study was to comparatively investigate the effects of eicosapentaenoic acid-enriched and docosahexaenoic acid-enriched phospholipids forage (EPA-PL and DHA-PL) and liposomes (lipo-EPA and lipo-DHA) on NAFLD and demonstrate the possible protective mechanisms involved. The additive doses of EPA-PL and DHA-PL in all treatment groups were 1% of total diets, respectively. The results showed that Lipo-EPA could significantly improve hepatic function by down-regulating orotic acid-induced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels by 55.6% and 34.2%, respectively (p < 0.01). Moreover, lipo-EPA exhibited excellent inhibition on the mRNA expression of SREBP-1c and FAS at the values of 0.454 ± 0.09 (p < 0.01) and 0.523 ± 0.08 (p < 0.01), respectively, thus ameliorating OA-induced NAFLD. Meanwhile, lipo-EPA could significantly suppress the SREBP-2 and HMGR levels (31.4% and 66.7%, p < 0.05, respectively). In addition, EPA-PL and lipo-DHA could also significantly suppress hepatic lipid accumulation mainly by enhancement of hepatic lipolysis and cholesterol efflux. Furthermore, DHA-PL played a certain role in inhibiting hepatic lipogenesis and accelerating cholesterol efflux. The results obtained in this work might contribute to the understanding of the biological activities of EPA/DHA-PL and liposomes and further investigation on its potential application values for food supplements.