Stress and ovarian hormone fluctuation are risk factors for postpartum depression (PPD). Previous studies suggested antidepressant-like effects of n-3 polyunsaturated fatty acids (PUFA), but their ...effect on dam animal with additional stress were not clear. The purpose of the present study was to investigate the hypothesis that n-3 PUFA improved PPD through the serotonergic and glutamatergic pathways by modulating miRNA. Rats were fed n-3 PUFA or control diet from gestation, with pup separation (PS) on postpartum days 2–14 and non-PS controls. N-3 PUFA reversed PS-induced depressive behaviors, including increased immobility, latencies to contact first pup and retrieve all pups, and decreased sucrose preference. N-3 PUFA also modulated the hypothalamic–pituitary–adrenal (HPA) axis by decreasing circulating levels of adrenocorticotropic hormone and corticosterone and expression of hypothalamic corticotrophin releasing factor and hippocampal miRNA-218 but increasing the hippocampal expression of glucocorticoid receptor. N-3 PUFA inhibited neuroinflammation by decreasing circulating levels of prostaglandin E2 and hippocampal expression of tumor necrosis factor-α, interleukin-6, and miRNA-155. In addition, n-3 PUFA up-regulated the serotonergic pathway by increasing circulating levels of serotonin and hippocampal expression of serotonin-1A receptor, cAMP response element binding protein (CREB), pCREB, brain-derived neurotrophic factor, and miRNA-182 but did not affect the glutamatergic pathway according to the hippocampal expression of N-methyl-D-aspartate receptor-2B. The present study suggested that n-3 PUFA improved PPD through the serotonergic pathway by modifying the HPA axis, neuroinflammation, and related miRNAs.
Background
Obesity is associated with enhanced lipid accumulation and the expansion of adipose tissue accompanied by hypoxia and inflammatory signalling. Investigation in human subcutaneous white ...adipose tissue (scWAT) in people living with obesity in which metabolic complications such as insulin resistance are yet to manifest is limited, and the mechanisms by which these processes are dysregulated are not well elucidated. Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have been shown to modulate the expression of genes associated with lipid accumulation and collagen deposition and reduce the number of inflammatory macrophages in adipose tissue from individuals with insulin resistance. Therefore, these lipids may have positive actions on obesity associated scWAT hypertrophy and inflammation.
Methods
To evaluate obesity-associated tissue remodelling and responses to LC n-3 PUFAs, abdominal scWAT biopsies were collected from normal weight individuals and those living with obesity prior to and following 12-week intervention with marine LC n-3 PUFAs (1.1 g EPA + 0.8 g DHA daily). RNA sequencing, qRT-PCR, and histochemical staining were used to assess remodelling- and inflammatory-associated gene expression, tissue morphology and macrophage infiltration.
Results
Obesity was associated with scWAT hypertrophy (
P
< 0.001), hypoxia, remodelling, and inflammatory macrophage infiltration (
P
= 0.023). Furthermore, we highlight the novel dysregulation of Wnt signalling in scWAT in non-insulin resistant obesity. LC n-3 PUFAs beneficially modulated the scWAT environment through downregulating the expression of genes associated with inflammatory and remodelling pathways (
P <
0.001), but there were altered outcomes in individuals living with obesity in comparison to normal weight individuals.
Conclusion
Our data identify dysregulation of Wnt signalling, hypoxia, and hypertrophy, and enhanced macrophage infiltration in scWAT in non-insulin resistant obesity. LC n-3 PUFAs modulate some of these processes, especially in normal weight individuals which may be preventative and limit the development of restrictive and inflammatory scWAT in the development of obesity. We conclude that a higher dose or longer duration of LC n-3 PUFA intervention may be needed to reduce obesity-associated scWAT inflammation and promote tissue homeostasis.
Clinical Trial Registration
www.isrctn.com
, identifier ISRCTN96712688.
•n-3 PUFA glycerides were enzymatically enriched by selective hydrolysis.•Lipase AY “Amano” 400SD showed remarkably hydrolytic discrimination against PUFA.•SFAs and MUFAs were released from ...triglycerides to obtain PUFA-enriched glycerides.•Addition of Ca2+ to the system led to the decrease of reaction time from 10 to 4 h.•PUFA content in algal oil after selective hydrolysis was up to 89.9%
Most natural oils are low in n-3 polyunsaturated fatty acids (n-3 PUFAs) content, which limits their application in health products. In this study, n-3 PUFAs in glyceride form were selectively enriched by lipase-mediated hydrolysis of n-3 PUFA-containing oils. First, commercial lipases were screened, and the lipase AY “Amano” 400SD from Candida cylindracea was the best choice in producing n-3 PUFA glycerides from tuna oil. Subsequently, the hydrolysis conditions were optimized. Under the optimal conditions, the highest n-3 PUFA content in the glyceride fraction was found to be 57.7% after enzymatic hydrolysis. Addition of Ca2+ to the system significantly shortened the reaction time from 10 to 4 h. When algal oil was used as substrate, total PUFA contents in the glyceride fraction were 89.9%. This study provides an efficient enzymatic process to produce n-3 PUFA-enriched glyceride concentrates and demonstrates that AY “Amano” 400SD can effectively discriminate against n-3 PUFAs during hydrolysis.
Fish and algae are the major sources of n-3 polyunsaturated fatty acids (n-3 PUFAs). Globally, there is a rapid increase in demand for n-3 PUFA-rich oils. Conventional oil production processes use ...high temperature and chemicals, compromising the oil quality and the environment. Hence, alternative green technologies have been investigated for producing oils from aquatic sources. While most of the studies have focused on the oil extraction and enrichment of n-3 PUFAs, less effort has been directed toward green refining of oils from fish and algae. Enzymatic processing and ultrasound-assisted extraction with environment-friendly solvents are the most promising green technologies for extracting fish oil, whereas pressurized extractions are suitable for extracting microalgae oil. Lipase-catalysed ethanolysis of fish and algae oil is a promising green technology for enriching n-3 PUFAs. Green refining technologies such as phospholipase- and membrane-assisted degumming deserve investigation for application in fish and algal oils. In the current review, we critically examined the currently existing research on technologies applied at each of the steps involved in the production of oils rich in n-3 PUFAs from fish and algae species. Special attention was placed on assessment of green technologies in comparison with conventional processing methods.
Nutrition, and particularly dietary energy intake, plays a fundamental role in reproductive function in cattle. There is some evidence that supplemental omega-3 dietary polyunsaturated fatty acids ...(n-3 PUFA) can exert positive effects on fertility. The objectives of this study were to evaluate the effect of dietary n-3 PUFA supplementation, post-insemination energy plane of nutrition and their interaction on embryo survival in cattle. Crossbred beef heifers (n = 185) were individually offered barley straw ad libitum and 6 kg DM of concentrate supplemented with either a rumen-protected source of saturated fatty acid (palmitic; control, CON) or a partially rumen-protected n-3 PUFA-enriched supplement (n-3 PUFA). Estrous was synchronised using two injections of PG administered at 11-d intervals and following artificial insemination (AI = Day 0) 179 heifers exhibiting oestrus were inseminated and assigned to one of two dietary treatments: (i) remain on their pre-insemination high dietary plane of nutrition (High) or (ii) restricted to 0.6 × estimated maintenance energy requirements (Low) in a 2 × 2 factorial design. The heifers were then maintained on their assigned diets until slaughter and embryo recovery on Day 16 (n = 92) or pregnancy diagnosis by ultrasound scanning at Day 30 post-AI (n = 87). Plasma concentrations of fatty acids, metabolites, insulin, progesterone (P4) and insulin-like growth factor 1 (IGF-1) were measured at appropriate intervals. Hepatic expression of mRNA for aldo-keto reductase (AKR1C), cytochrome P450 2C (CYP 2C) and cytochrome P450 3A (CYP 3A) was examined. The n-3 PUFA supplementation increased plasma n-3 PUFA concentration (P < 0.05) and reduced n-6: n-3 PUFA ratio (P < 0.05). Plasma IGF-1 was higher for n-3 PUFA relative to the CON (P < 0.05) and for High compared with Low plane of nutrition post-AI (P < 0.05) groups. A low plane of nutrition post-AI increased plasma concentrations of progesterone from Days 7–16 after insemination (P < 0.001) but reduced embryo length (P < 0.001). Supplementation with n-3 PUFA reduced and tended to reduce hepatic expression of CYP2C (P = 0.01) and CYP3A (P = 0.08), respectively. However, while dietary n-3 PUFA supplementation and an abrupt reduction in nutrient status following insemination elevated plasma concentrations of n-3 PUFA and mid and late phase P4, respectively, there was no effect of either PUFA supplementation or post-insemination plane of nutrition on embryo survival.
•Dietary supplementation of beef heifers with n-3 PUFA increased plasma concentrations of n-3 PUFA and IGF-1 and led to larger embryos 16 days after insemination. However this did not result in improved pregnancy rates.•There was evidence for a reduction in the hepatic expression of some key genes coding for enzymes involved in progesterone degradation in heifers supplemented with n-3 PUFA.•Restricting dietary allowance directly after insemination reduced systemic concentrations of IGF-1 and embryo length, increased progesterone concentrations during the mid to late luteal phase but did not affect pregnancy rate.
Dietary n-3 long chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to be natural doping agents in migratory shorebirds, enabling prolonged flight by increasing membrane fluidity and ...oxidative capacity of the flight muscles. Animals can obtain n-3 LCPUFAs from the diet or by conversion of dietary α-linolenic acid, 18:3 n-3. However, the capacity to meet n-3 LCPUFA requirements from 18:3 n-3 varies among species. Direct tests of muscle oxidative enhancement and fatty acid conversion capacity are lacking in marine shorebirds that evolved eating diets rich in n-3 LCPUFAs. We tested whether the presence and type of dietary fatty acids influence the fatty acid composition and flight muscle oxidative capacity in western sandpipers (Calidris mauri). Sandpipers were fed diets low in n-3 PUFAs, high in 18:3 n-3, or high in n-3 LCPUFAs. Dietary fatty acid composition was reflected in multiple tissues, and low intake of n-3 LCPUFAs decreased the abundance of these fatty acids in all tissues, even with a high intake of 18:3 n-3. This suggests that 18:3 n-3 cannot replace n-3 LCPUFAs, and dietary n-3 LCPUFAs are required for sandpipers. Flight muscle indicators of enzymatic oxidative capacity and regulators of lipid metabolism did not change. However, the n-3 LCPUFA diet was associated with increased FAT/CD36 mRNA expression, potentially benefitting fatty acid transport during flight. Our study suggests that flight muscle lipid oxidation is not strongly influenced by n-3 PUFA intake. The type of dietary n-3 PUFA strongly influences the abundance of n-3 LCPUFAs in the body and could still impact whole-animal performance.
n-3 Polyunsaturated fatty acids (n-3 PUFA) has been widely used in foods, and pharmaceutical products due to its beneficial effects. The content of n-3 PUFA in natural oils is usually low, which ...decreases its added value. Thus, there is an increasing demand on the market for n-3 PUFA concentrates. This review firstly introduces the differences in bioavailability and oxidative stability between different types of PUFA concentrate (free fatty acid, ethyl ester and acylglycerol), and then provides a comprehensive discussion of different methods for enrichment of lipids with n-3 PUFA including physical-chemical methods and enzymatic methods. Lipases used for catalyzing esterification, transesterification and hydrolysis reactions play an important role in the production of highly enriched various types of n-3 PUFA concentrates. Lipase-catalyzed alcoholysis or hydrolysis reactions are the mostly employed method to prepare high-quality n-3 PUFA of structural acylglycerols. Although many important advantages offered by lipases in enrichment of n-3 PUFA, the high cost of enzyme limits its industrial-scale production. Further research should focus on looking for biological enzymes with extraordinary catalytic ability and clear selectivity. Other novel technologies such as protein engineering and immobilization may be needed to modify lipases to improve its selectivity, catalytic ability and reuse.
Esencijalne masne kiseline EPA i DHA imaju posebnu ulogu u fiziološkim procesima i preveniraju kardiovaskularnih bolesti kod ljudi i zato je obogaćivanje jaja s n-3 PUFA predmet brojnih istraživanja. ...Jaja se mogu obogatiti s n-3 PUFA ako se nesilice hrane smjesama koje sadrže biljna ulja, posebice laneno i repičino te riblje ulje i mikroalge Schizochytrium limacinum. Rezultati naših istraživanja pokazuju najbolju učinkovitost deponiranja ALA, EPA i DHA te Σn-3 PUFA u lipide žumanjaka ako hrana nesilica sadrži kombinaciju ribljeg (1,5 %) i lanenog (3,5 %), odnosno 1,5 % ribljeg ulja i 3,5 % biljnih ulja. Zamjena ribljeg ulja (1,5 %) s mikroalgama Schizochytrium limacinum (1,5 %) pokazala se također efikasnom u obogaćivanju jaja s n-3 PUFA. Rezultati naših istraživanja kao i drugih autora pokazuju najbolju učinkovitost deponiranja Σn-3 PUFA u jaja upotrebom lanenog i ribljeg ulja u hranidbi nesilica. Modulacijom hranidbenih tretmana postignuto je obogaćivanje jaja s n-3 PUFA u većem broju istraživanja, do koncentracije na temelju koje se jaja mogu smatrati funkcionalnim proizvodom. Pri tome je smanjen omjer Σn-6/Σn-3 PUFA do poželjnih 4-5:1 vrijednosti.
The essential fatty acids EPA and DHA have a special role in physiological processes and prevent cardiovascular diseases in humans, and that is the reason for numerous studies for enriching eggs with n-3 PUFA. Eggs can be enriched with n-3 PUFA if laying hens are fed mixtures that contains vegetable oils, especially linseed oil and rapeseed oil, as well as fish oil and the microalgae Schizochytrium limacinum. The obtained results show the best efficiency of depositing ALA, EPA and DHA and Σn-3 PUFA in yolk lipids if the feed of laying hens contains a combination of fish (1.5%) and linseed (1,.5%) or fish oil (1.5%) and vegetable oils (3.5%). The supstitution 1.5% of fish oil with the microalgae Schizochytrium limacinum (1.5%) was also effective in enriching eggs with n-3 PUFA. The results of our study and those of other authors show that the best efficiency of depositing Σn-3 PUFA in eggs is by using linseed and fish oil in the feeding of laying hens. By modulating nutritional treatments, enrichment of eggs with n-3 PUFA was achieved in a large number of studies, up to a concentration based on which eggs can be considered a functional product. In doing so, the Σn-6/Σn-3 PUFA ratio was reduced to the desirable 4-5:1 value.
Background:
While the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on cardiac ischemia-reperfusion (IR) injury have been previously reported, limited data are available regarding how ...these fatty acids affect membrane receptors and their downstream signaling following IR injury. We aimed to identify potential receptors activated by n-3 PUFAs in IR hearts to understand the regulatory mechanisms of these receptors.
Methods:
We used
fat-1
mice, which naturally have elevated levels of n-3 PUFAs, and C57BL/6J mice as a control group to create a myocardial IR injury model through Langendorff perfusion. We assessed the impact of endogenous n-3 PUFAs on left ventricular function, myocardial infarct size, myocardial apoptosis, and ATP production. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify molecular targets affected by n-3 PUFAs. Based on these analyses we then treated IR hearts of WT and
fat-1
mice with an antagonist (ML221) or an agonist (apelin-13) for the predicted receptor to assess cardiac contractile function and intracellular signaling pathways. An
in vitro
hypoxia-reoxygenation (HR) model was also used to confirm the effects of n-3 PUFAs on the examined intracellular signaling pathways.
Results:
Endogenous n-3 PUFAs protected cardiac structure and function in post-IR hearts, and modulated phosphorylation patterns in the PI3K-AKT-mTOR signaling pathways. RNA-seq analysis revealed that n-3 PUFAs affected multiple biological processes as well as levels of the apelin receptor (APLNR). Consistent with a role for the PLNNR, ML221 synchronized the activation of the PI3K-AKT-mTOR signaling axis, suppressed the expression of PKCδ and phosphorylated p38α, upregulated PKCε expression, upregulated or restored the phosphorylation of myofilaments, and prevented myocardial injury and contractile dysfunction in WT IR hearts. By contrast, apelin-13 disrupted the PI3K-AKT-mTOR signaling axis in post-IR
fat-1
hearts. The phosphorylation signaling targeted by APLNR inhibition in post-IR
fat-1
hearts was also observed after treating HR cells with eicosatetraenoic acid (EPA).
Conclusion:
Endogenous n-3 PUFAs protect against post-IR injury and preserve cardiac contractile function possibly through APLNR inhibition. This inhibition synchronizes the PI3K-AKT-mTOR axis, suppresses detrimental phosphorylation signaling, and restores or increases myofilament phosphorylation in post-IR hearts. The beneficial effects observed in
fat-1
transgenic mouse hearts can be attributed, at least in part, to elevated EPA levels. This study is the first to demonstrate that n-3 PUFAs protect hearts against IR injury through APLNR inhibition.
Omega-3 polyunsaturated fatty acids (n-3 PUFA) of marine origin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have been long studied for their therapeutic potential in the context of ...type 2 diabetes, insulin resistance, and glucose homeostasis. Glaring discordance between observations in animal and human studies precludes, to date, any practical application of n-3 PUFA as nutritional therapeutics against insulin resistance in humans. Our objective in this review is to summarize current knowledge and provide an up-to-date commentary on the therapeutic value of EPA and DHA supplementation for improving insulin sensitivity in humans. We also sought to discuss potential mechanisms of n-3 PUFA action in target tissues, in specific skeletal muscle, based on our recent work, as well as in liver and adipose tissue. We conducted a literature search to include all preclinical and clinical studies performed within the last two years and to comment on representative studies published earlier. Recent studies support a growing consensus that there are beneficial effects of n-3 PUFA on insulin sensitivity in rodents. Observational studies in humans are encouraging, however, the vast majority of human intervention studies fail to demonstrate the benefit of n-3 PUFA in type 2 diabetes or insulin-resistant non-diabetic people. Nevertheless, there are still several unanswered questions regarding the potential impact of n-3 PUFA on metabolic function in humans.
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