Unexpected omega-3 activities in intracellular lipolysis and macrophage foaming revealed by fluorescence lifetime imaging.

Omega-3 polyunsaturated fatty acids (PUFA) found primarily in fish oil have been a popular supplement for cardiovascular health because they can substantially reduce circulating triglyceride levels in the bloodstream to prevent atherosclerosis. Beyond this established extracellular activity, here, we report a mode of action of PUFA, regulating intracellular triglyceride metabolism and lipid droplet (LD) dynamics. Real-time imaging of the subtle and highly dynamic changes of intracellular lipid metabolism was enabled by a fluorescence lifetime probe that addressed the limitations of intensity-based fluorescence quantifications. Surprisingly, we found that among omega-3 PUFA, only docosahexaenoic acid (DHA) promoted the lipolysis in LDs and reduced the overall fat content by approximately 50%, and consequently helped suppress macrophage differentiation into foam cells, one of the early steps responsible for atherosclerosis. Eicosapentaenoic acid, another omega-3 FA in fish oil, however, counteracted the beneficial effects of DHA on lipolysis promotion and cell foaming prevention. These in vitro findings warrant future validation in vivo.

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

SCOPE: 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. METHODS AND RESULTS: 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 ß-oxidation related protein expression levels. CONCLUSIONS: This work elucidates that DHA has improved NAFLD by suppressing endocannabinoid system.

Dietary intake of different ratios of ARA/DHA in early stages and its impact on infant development.

Long-chain polyunsaturated fatty acids (LC-PUFAs), arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3) are essential in the development of infants. ARA and DHA from breast milk or infant formula are the main sources of access for infants to meet their physiological and metabolic needs. The ratio of ARA to DHA in breast milk varies among regions and different lactation stages. Different ratios of ARA and DHA mainly from algal oil, animal fat, fish oil, and microbial oil, are added to infant formula in different regions and infant age ranges. Supplementing with appropriate ratios of ARA and DHA during infancy promotes brain, neural, visual, and other development aspects. In this review, we first introduced the current intake status of ARA and DHA in different locations, lactation stages, and age ranges in breast milk and infant formula. Finally, we discussed the effect of different ratios of ARA and DHA on infant development. This review provided a comprehensive research basis for the nutritional research of infants who consume different ratios of ARA and DHA.

Optimizing ARA and DHA in infant formula: A systematic review of global trends, regional disparities, and considerations for precision nutrition.

In the context of precision nutrition, the addition of ARA and DHA in infant formula needs to consider more factors. This study conducted a comprehensive literature review, including 112 relevant Chinese and English articles, to summarize and analyze the global levels of ARA, DHA, and the ARA/DHA ratio in breast milk. The data were correlated with local aquatic products intake and children's IQ. The results indicated that the average level of DHA in breast milk across regions is lower than that of ARA. Variations in DHA content were identified as a primary factor influencing ARA/DHA ratio fluctuations. Breast milk ARA and DHA levels decrease with prolonged lactation periods but increase over the past 22 years. Correlation analysis revealed a significant positive relationship between aquatic products intake and breast milk DHA levels (r = 0.64, p < 0.05). Breast milk DHA levels also showed a significant positive correlation with children's IQ (r = 0.67, p < 0.01). Stable breast milk ARA content did not exhibit significant correlations with aquatic products intake or children's IQ (r = 0, p > 0.05). Among 22 infant formula products available in China, only 5 had ARA levels within the range of breast milk. Most formula products had higher ARA levels than DHA, resulting in ARA/DHA ratios generally exceeding 1. The temporal and spatial variability in breast milk ARA and DHA levels may lead to diverse health outcomes in infants. Therefore, the addition of ARA and DHA in infant formula should consider this variability, including the molecular forms and positional isomerism of the added ARA and DHA. Additionally, considering the impact of different cognitive development tests and infant's gene expression on formula assessment results, there is a need to establish a more comprehensive infant health assessment system to guide the addition of ARA and DHA in formula.

Dietary docosahexaenoic acid supplementation inhibits acute pulmonary transcriptional and autoantibody responses to a single crystalline silica exposure in lupus-prone mice.

Introduction: Workplace exposure to respirable crystalline silica (cSiO2) has been epidemiologically linked to lupus. Consistent with this, repeated subchronic intranasal cSiO2 instillation in lupus-prone NZBWF1 mice induces inflammation-/autoimmune-related gene expression, ectopic lymphoid tissue (ELT), autoantibody (AAb) production in the lung within 5 to 13 wk followed systemic AAb increases and accelerated onset and progression of glomerulonephritis within 13 to 17 wk. Interestingly, dietary docosahexaenoic acid (DHA) supplementation suppresses these pathologic effects, but the underlying molecular mechanisms remain unclear. Methods: This study aimed to test the hypothesis that dietary DHA supplementation impacts acute transcriptional and autoantibody responses in the lungs of female NZBWF1 mice 1 and 4 wk after a single high-dose cSiO2 challenge. Groups of mice were initially fed a control (Con) diet or a DHA-containing diet (10 g/kg). Cohorts of Con- and DHA-fed were subjected to a single intranasal instillation of 2.5 mg cSiO2 in a saline vehicle (Veh), while a Con-fed cohort was instilled with Veh only. At 1 and 4 wk post-instillation (PI), we compared cSiO2's effects on innate-/autoimmune-related gene expression and autoantibody (AAb) in lavage fluid/lungs of Con- and DHA-fed mice and related these findings to inflammatory cell profiles, histopathology, cell death, and cytokine/chemokine production. Results: DHA partially alleviated cSiO2-induced alterations in total immune cell and lymphocyte counts in lung lavage fluid. cSiO2-triggered dead cell accumulation and levels of inflammation-associated cytokines and IFN-stimulated chemokines were more pronounced in Con-fed mice than DHA-fed mice. Targeted multiplex transcriptome analysis revealed substantial upregulation of genes associated with autoimmune pathways in Con-fed mice in response to cSiO2 that were suppressed in DHA-fed mice. Pathway analysis indicated that DHA inhibited cSiO2 induction of proinflammatory and IFN-regulated gene networks, affecting key upstream regulators (e.g., TNFα, IL-1ß, IFNAR, and IFNγ). Finally, cSiO2-triggered AAb responses were suppressed in DHA-fed mice. Discussion: Taken together, DHA mitigated cSiO2-induced upregulation of pathways associated with proinflammatory and IFN-regulated gene responses within 1 wk and reduced AAb responses by 4 wk. These findings suggest that the acute short-term model employed here holds substantial promise for efficient elucidation of the molecular mechanisms through which omega-3 PUFAs exert protective effects against cSiO2-induced autoimmunity.

Effects of DHA on cognitive dysfunction in aging and Alzheimer's disease: The mediating roles of ApoE.

The prevalence of Alzheimer's disease (AD) continues to rise due to the increasing aging population. Among the various genetic factors associated with AD, apolipoprotein E (ApoE), a lipid transporter, stands out as the primary genetic risk factor. Specifically, individuals carrying the ApoE4 allele exhibit a significantly higher risk. However, emerging research indicates that dietary factors play a prominent role in modifying the risk of AD. Docosahexaenoic acid (DHA), a prominent ω-3 fatty acid, has garnered considerable attention for its potential to ameliorate cognitive function. The intricate interplay between DHA and the ApoE genotype within the brain, which may influence DHA's utilization and functionality, warrants further investigation. This review meticulously examines experimental and clinical studies exploring the effects of DHA on cognitive decline. Special emphasis is placed on elucidating the role of ApoE gene polymorphism and the underlying mechanisms are discussed. These studies suggest that early DHA supplementation may confer benefits to cognitively normal older adults carrying the ApoE4 gene. However, once AD develops, ApoE4 non-carriers may experience greater benefits compared to ApoE4 carriers, although the overall effectiveness of DHA supplementation at this stage is limited. Potential mechanisms underlying these differential effects may include accelerated DHA catabolism in ApoE4 carriers, impaired transport across the blood-brain barrier (BBB), and compromised lipidation and circulatory function in ApoE4 carriers. Thus, the supplementation of DHA may represent a potential intervention strategy aimed at compensating for these deficiencies in ApoE4 carriers prior to the onset of AD.

n-3 PUFAs Show Promise as Adjuvants in Chemotherapy, Enhancing their Efficacy while Safeguarding Hematopoiesis and Promoting Bone Generation.

Cancer ranks as the second leading cause of mortality in high-income countries, underscoring the critical need for effective therapeutic strategies. One prominent approach, chemotherapy, is widely employed for treating solid tumors. However, the significant adverse effects associated with chemotherapy, notably myeloablation and osteonecrosis, impart considerable challenges by compromising immune function and diminishing patients' quality of life. Furthermore, the emergence of chemotherapy resistance poses a formidable hurdle in achieving successful cancer treatment outcomes. In this context, the focus is on exploring alternative approaches to enhance the efficacy of cancer treatment and mitigate its adverse consequences. Among these approaches, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two n-3 polyunsaturated fatty acids (PUFAs), have garnered substantial interest. These PUFAs exhibit the potential to influence membrane lipid composition and modulate critical gene expressions associated with cancer, such as Bcl-2, PI3K, NF-κB, and phosphorylated Akt, thereby potentially reducing cancer risk. Moreover, emerging evidence highlights their ability to augment chemotherapy efficacy, particularly in drug-resistant cancer cells. Importantly, both preclinical and clinical investigations have provided compelling evidence supporting the protective effects of n-3 PUFAs on healthy cells. Leveraging these findings, there has been growing attention on the exploration of n-3 PUFAs as adjuvants to chemotherapy. This strategic approach holds promise in mitigating the adverse effects linked to chemotherapy, notably myeloablation and osteonecrosis, while simultaneously enhancing its effectiveness in combating cancer. This comprehensive review delves into the multifaceted attributes of n-3 PUFAs, encompassing their cytotoxic properties, potential as chemopreventive agents, and their prospective role in ameliorating the adverse effects commonly associated with chemotherapy, with a particular emphasis on myeloablation and osteonecrosis. By elucidating the intricate interplay between n-3 PUFAs and cancer treatment paradigms, this review contributes to the expanding body of knowledge aimed at refining cancer therapeutic strategies and enhancing patient outcomes.

Fish oil-derived n-3 polyunsaturated fatty acids downregulate aquaporin 9 protein expression of liver and white adipose tissues in diabetic KK mice and 3T3-L1 adipocytes.

Aquaporin 9 (AQP9) is an integral membrane protein that facilitates glycerol transport in hepatocytes and adipocytes. Glycerol is necessary as a substrate for gluconeogenesis in the physiological fasted state, suggesting that inhibiting AQP9 function may be beneficial for treating type 2 diabetes associated with fasting hyperglycemia. The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are rich in fish oil and lower the risk of metabolic syndrome; however, the effects of EPA and DHA on AQP9 expression in obese and type 2 diabetes are unclear. The KK mouse is an animal model of obesity and type 2 diabetes because of the polymorphisms on leptin receptor gene, which results in a part of cause for obese and diabetic conditions. In this study, we determined the effect of fish oil-derived n-3 PUFA on AQP9 protein expression in the liver and white adipose tissue (WAT) of KK mice and mouse 3T3-L1 adipocytes. The expression of AQP9 protein in the liver, epididymal WAT, and inguinal WAT were markedly decreased following fish oil administration. We also demonstrated that n-3 PUFAs, such as DHA, and to a lesser extent EPA, downregulated AQP9 protein expression in 3T3-L1 adipocytes. Our results suggest that fish oil-derived n-3 PUFAs may regulate the protein expressions of AQP9 in glycerol metabolism-related organs in KK mice and 3T3-L1 adipocytes.

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 ß-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.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Comprehensive proteomic analysis reveals omega-3 fatty acids to counteract endotoxin-stimulated metabolic dysregulation in porcine enterocytes.

Omega-3 polyunsaturated fatty acids (n-3 PUFA), such as the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are reported to beneficially affect the intestinal immunity. The biological pathways modulated by n-3 PUFA during an infection, at the level of intestinal epithelial barrier remain elusive. To address this gap, we investigated the proteomic changes induced by n-3 PUFA in porcine enterocyte cell line (IPEC-J2), in the presence and absence of lipopolysaccharide (LPS) stress conditions using shotgun proteomics analysis integrated with RNA-sequencing technology. A total of 33, 85, and 88 differentially abundant proteins (DAPs) were identified in cells exposed to n-3 PUFA (DHA:EPA), LPS, and n-3 PUFA treatment followed by LPS stimulation, respectively. Functional annotation and pathway analysis of DAPs revealed the modulation of central carbon metabolism, including the glycolysis/gluconeogenesis, pentose phosphate pathway, and oxidative phosphorylation processes. Specifically, LPS caused metabolic dysregulation in enterocytes, which was abated upon prior treatment with n-3 PUFA. Besides, n-3 PUFA supplementation facilitated enterocyte development and lipid homeostasis. Altogether, this work for the first time comprehensively described the biological pathways regulated by n-3 PUFA in enterocytes, particularly during endotoxin-stimulated metabolic dysregulation. Additionally, this study may provide nutritional biomarkers in monitoring the intestinal health of human and animals on n-3 PUFA-based diets.

Omega-3 Lipid Mediators: Modulation of the M1/M2 Macrophage Phenotype and Its Protective Role in Chronic Liver Diseases.

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties, by modulating the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLDs, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3s and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. The aim of this article was to analyze the emerging role of omega-3 FAs and their SPMs in the context of macrophage polarization, with special interest in the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment, focused on CLDs and the development of novel therapeutic strategies.

Lycium barbarum glycopeptide alleviates neuroinflammation in spinal cord injury via modulating docosahexaenoic acid to inhibiting MAPKs/NF-kB and pyroptosis pathways.

BACKGROUND: Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear. AIMS: In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments. METHODS: SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR. RESULTS: In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways. CONCLUSIONS: In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.

Effect of Docosahexaenoic Acid Encapsulation with Whey Proteins on Rat Growth and Tissue Endocannabinoid Profile.

Modifying the food structure allows a nutrient to be delivered differently, which can modify not only its digestion process but also its subsequent metabolism. In this study, rats received 3 g of omelette daily containing docosahexaenoic acid (DHA) as crude oil or previously encapsulated with whey proteins, whereas a control group received a DHA-free omelette. The results showed that DHA encapsulation markedly induced a different feeding behaviour so animals ate more and grew faster. Then, after four weeks, endocannabinoids and other N-acyl ethanolamides were quantified in plasma, brain, and heart. DHA supplementation strongly reduced endocannabinoid derivatives from omega-6 fatty acids. However, DHA encapsulation had no particular effect, other than a great increase in the content of DHA-derived docosahexaenoyl ethanolamide in the heart. While DHA supplementation has indeed shown an effect on cannabinoid profiles, its physiological effect appears to be mediated more through more efficient digestion of DHA oil droplets in the case of DHA encapsulation. Thus, the greater release of DHA and other dietary cannabinoids present may have activated the cannabinoid system differently, possibly more locally along the gastrointestinal tract. However, further studies are needed to evaluate the synergy between DHA encapsulation, fasting, hormones regulating food intake, and animal growth.

Branched-Long-Chain Monomethyl Fatty Acids: Are They Hidden Gems?

Branched-long-chain monomethyl fatty acids (BLCFA) are consumed daily in significant amounts by humans in all stages of life. BLCFA are absorbed and metabolized in human intestinal epithelial cells and are not only oxidized for energy. Thus far, BLCFA have been revealed to possess versatile beneficial bioactivities, including cytotoxicity to cancer cells, anti-inflammation, lipid-lowering, reducing the risk of metabolic disorders, maintaining normal ß cell function and insulin sensitivity, regulation of development, and mitigating cerebral ischemia/reperfusion injury. However, compared to other well-studied dietary fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), BLCFA has received disproportionate attention despite their potential importance. Here we outlined the major food sources, estimated intake, absorption, and metabolism in human cells, and bioactive properties of BLCFA with a focus on the bioactive mechanisms to advocate for an increased commitment to BLCFA investigations. Humans were estimated to absorb 6-5000 mg of dietary BLCFA daily from fetus to adult. Notably, iso-15:0 inhibited the growth of prostate cancer, liver cancer and T-cell non-Hodgkin lymphomas in rodent models at the effective doses of 35-105 mg/kg/day, 70 mg/kg/day, and 70 mg/kg/day, respectively. Feeding formula prepared with 20% w/w BLCFA mixture to neonatal rats with enterocolitis mitigated the intestine inflammation. Iso-15:0 at doses of 10, 40, and 80 mg/kg relieved brain ischemia/reperfusion injury in rats. In the future, it is crucial to conduct research to establish the epidemiology of BLCFA intake and their impacts on health outcomes in humans as well as to fully uncover the underlying mechanisms for their bioactivities.

Supplementation of Medium-Chain Triglycerides Combined with Docosahexaenoic Acid Inhibits Amyloid Beta Protein Deposition by Improving Brain Glucose Metabolism in APP/PS1 Mice.

The deterioration of brain glucose metabolism predates the clinical onset of Alzheimer's disease (AD). Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA) positively improve brain glucose metabolism and decrease the expression of AD-related proteins. However, the effects of the combined intervention are unclear. The present study explored the effects of the supplementation of MCTs combined with DHA in improving brain glucose metabolism and decreasing AD-related protein expression levels in APP/PS1 mice. The mice were assigned into four dietary treatment groups: the control group, MCTs group, DHA group, and MCTs + DHA group. The corresponding diet of the respective groups was fed to mice from the age of 3 to 11 months. The results showed that the supplementation of MCTs combined with DHA could increase serum octanoic acid (C8:0), decanoic acid (C10:0), DHA, and ß-hydroxybutyrate (ß-HB) levels; improve glucose metabolism; and reduce nerve cell apoptosis in the brain. Moreover, it also aided with decreasing the expression levels of amyloid beta protein (Aß), amyloid precursor protein (APP), ß-site APP cleaving enzyme-1 (BACE1), and presenilin-1 (PS1) in the brain. Furthermore, the supplementation of MCTs + DHA was significantly more beneficial than that of MCTs or DHA alone. In conclusion, the supplementation of MCTs combined with DHA could improve energy metabolism in the brain of APP/PS1 mice, thus decreasing nerve cell apoptosis and inhibiting the expression of Aß.

The potential of a combination of pungent spices as a novel supplement in gilthead seabream (Sparus aurata) diets to aid in the strategic use of fish oil in aquafeeds: a holistic perspective.

This work studied the potential of a combination of pungent spices (capsicum, black pepper, ginger, and cinnamaldehyde) to be used as a supplement in diets of gilthead seabream (Sparus aurata; 44.1 ± 4.2 g). During 90 days, fish were fed three experimental diets with low inclusion of fish oil and containing poultry fat as the main source of lipids, supplemented with graded levels of the tested supplement: 0 (control), 0.1 (SPICY0.1%), and 0.15% (SPICY0.15%). As a result, the pungent spices enhanced the growth performance, the activity of the bile-salt-activated lipase in the intestine, and decreased fat deposit levels within enterocytes. The SPICY0.1% diet reduced the feed conversion ratio and the perivisceral fat index and lipid deposits in the liver. Moreover, the ratio of docosahexaenoic acid/eicosapentaenoic acid in fillet increased in fish fed the SPICY0.1% diet, while the hepatic levels of docosahexaenoic acid and total n-3 polyunsaturated fatty acids increased in fish fed the SPICY0.15% diet. Furthermore, there was an effect on the expression of some biomarkers related to lipid metabolism in 2-h postprandial fish (fasn, elovl6, scd1b, cyp7a1, lpl, and pparß), and in 48 h fasted-fish fed with the SPICY0.1% diet, a regulation of the intestinal immune response was indicated. However, no significant differences were found in lipid apparent digestibility and proximate macronutrient composition. The spices did not affect biomarkers of hepatic or oxidative stress. No differences in microbial diversity were found, except for an increase in Simpson's Index in the posterior intestine of fish fed the SPICY0.1% diet, reflected in the increased relative abundance of the phylum Chloroflexi and lower relative abundances of the genera Campylobacter, Corynebacterium, and Peptoniphilus. In conclusion, the supplementation of gilthead seabream diets with pungent spices at an inclusion of 0.1% was beneficial to enhance growth performance and feed utilization; reduce fat accumulation in the visceral cavity, liver, and intestine; and improve the fish health status and condition. Results suggest that the tested supplement can be used as part of a nutritional strategy to promote a more judicious use of fish oil in fish diets due to its decreasing availability and rising costs.

DHA alleviated hepatic and adipose inflammation with increased adipocyte browning in high-fat diet-induced obese mice.

Obesity is associated with accumulation of inflammatory immune cells in white adipose tissue, whereas thermogenic browning adipose tissue is inhibited. Dietary fatty acids are important nutritional components and several clinical and experimental studies have reported beneficial effects of docosahexaenoic acid (DHA) on obesity-related metabolic changes. In this study, we investigated effects of DHA on hepatic and adipose inflammation and adipocyte browning in high-fat diet-induced obese C57BL/6J mice, and in vitro 3T3-L1 preadipocyte differentiation. Since visceral white adipose tissue has a close link with metabolic abnormality, epididymal adipose tissue represents current target for evaluation. A course of 8-week DHA supplementation improved common phenotypes of obesity, including improvement of insulin resistance, inhibition of macrophage M1 polarization, and preservation of macrophage M2 polarization in hepatic and adipose tissues. Moreover, dysregulated adipokines and impaired thermogenic and browning molecules, considered obesogenic mechanisms, were improved by DHA, along with parallel alleviation of endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and mitochondrial DNA stress-directed innate immunity. During 3T3-L1 preadipocytes differentiation, DHA treatment decreased lipid droplet accumulation and increased the levels of thermogenic, browning, and mitochondrial biogenesis molecules. Our study provides experimental evidence that DHA mitigates obesity-associated inflammation and induces browning of adipose tissue in visceral epididymal adipose tissue. Since obesity is associated with metabolic abnormalities across tissues, our findings indicate that DHA may have potential as part of a dietary intervention to combat obesity.

Comparison of the effect of various sources of saturated fatty acids on infant follow-on formulas oxidative stability and nutritional profile.

Fortification of infant follow-on formulas (IFF) with docosahexaenoic acid (DHA), which is prone to lipid oxidation, is required by European regulation. This study aimed to identify lipid formulation parameters that improve the nutritional profile and oxidative stability of IFF. Model IFF were formulated using different lipid and emulsifier sources, including refined (POM) or unrefined red palm oil (RPOM), coconut oil (COM), dairy fat (DFOM), soy lecithin, and dairy phospholipids (DPL). After an accelerated storage, RPOM and DFOM with DPL had improved oxidative stability compared to other IFF. Specifically, they had a peroxide value twice lower than POM and 20% less loss of tocopherols for DFOM-DPL. This higher stability was mainly explained by the presence of compounds such as carotenoids in RPOM and sphingomyelin in DFOM-DPL very likely acting synergistically with tocopherols. Incorporation of dairy lipids and carotenoids into DHA-enriched IFF compositions seems promising to enhance their stability and nutritional quality.

A review of recent studies on the enrichment of eggs and poultry meat with omega-3 polyunsaturated fatty acids: novel findings and unanswered questions.

Studies from our laboratory over the past decade have yielded new information with regard to the dietary enrichment of eggs and poultry meat with omega-3 (n-3) polyunsaturated fatty acids (PUFA) but have also generated a number of unanswered questions. In this review, we summarize the novel findings from this work, identify knowledge gaps, and offer possible explanations for some perplexing observations. Specifically discussed are: 1) Why feeding laying hens and broilers an oil rich in stearidonic acid (SDA; 18:4 n-3), which theoretically bypasses the putative rate-limiting step in the hepatic n-3 PUFA biosynthetic pathway, does not enrich egg yolks and tissues with very long-chain (VLC; ≥20 C) n-3 PUFA to the same degree as obtained by feeding birds oils rich in preformed VLC n-3 PUFA; 2) Why in hens fed an SDA-rich oil, SDA fails to accumulate in egg yolk but is readily incorporated into adipose tissue; 3) How oils rich in oleic acid (OA; 18:1 n-9), when co-fed with various sources of n-3 PUFA, attenuates egg and tissue n-3 PUFA contents or rescues egg production when co-fed with a level of docosahexaenoic acid (DHA; 22:6 n-3) that causes severe hypotriglyceridemia; and 4) Why the efficiency of VLC n-3 PUFA deposition into eggs and poultry meat is inversely related to the dietary content of α-linolenic acid (ALA; 18:3 n-3), SDA, or DHA.