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Neurobiology of Stress Jul 2024Depression is increasingly diagnosed in adolescence, necessitating specific prevention and treatment methods. However, there is a lack of animal models mimicking...
INTRODUCTION
Depression is increasingly diagnosed in adolescence, necessitating specific prevention and treatment methods. However, there is a lack of animal models mimicking juvenile depression. This study explores a novel model using ultrasound (US) stress in juvenile mice.
METHODS
We employed the US stress model in one-month-old C57/BL6 mice, exposing them to alternating ultrasound frequencies (20-25 kHz and 25-45 kHz) for three weeks. These frequencies correspond to negative and neutral emotional states in rodents and can induce a depressive-like syndrome. Concurrently, mice received either an omega-3 food supplement (FS) containing eicosapentaenoic acid (EPA; 0.55 mg/kg/day) and docosahexaenoic acid (DHA; 0.55 mg/kg/day) or a vehicle. Post-stress, we evaluated anxiety- and depressive-like behaviors, blood corticosterone levels, brain expression of pro-inflammatory cytokines, and conducted metabolome analysis of brain, liver and blood plasma.
RESULTS
US-exposed mice treated with vehicle exhibited decreased sucrose preference, a sign of anhedonia, a key feature of depression, increased anxiety-like behavior, elevated corticosterone levels, and enhanced TNF and IL-1β gene expression in the brain. In contrast, US-FS mice did not display these changes. Omega-3 supplementation also reduced anxiety-like behavior in non-stressed mice. Metabolomic analysis revealed US-induced changes in brain energy metabolism, with FS increasing brain sphingomyelin. Liver metabolism was affected by both US and FS, while plasma metabolome changes were exclusive to FS. Brain glucose levels correlated positively with activity in anxiety tests.
CONCLUSION
Chronic omega-3 intake counteracted depressive- and anxiety-like behaviors in a US model of juvenile depression in mice. These effects likely stem from the anti-inflammatory properties of the supplement, suggesting potential therapeutic applications in juvenile depression.
PubMed: 38912378
DOI: 10.1016/j.ynstr.2024.100646 -
Journal of Dairy Science Jun 2024Our objective was to compare abomasal infusions of linoleic (18:2n-6) and α-linolenic (18:3n-3) acids on the enrichment of n-6 and n-3 fatty acids (FA) into the plasma...
Our objective was to compare abomasal infusions of linoleic (18:2n-6) and α-linolenic (18:3n-3) acids on the enrichment of n-6 and n-3 fatty acids (FA) into the plasma lipid fractions of lactating dairy cows and evaluate their potential carryover effects in plasma lipid fractions post-infusion. Six rumen-cannulated multiparous Holstein cows (252 ± 33 d in milk) were fed the same diet and assigned to 1 of 2 treatments in a completely randomized design with repeated measures. Treatments were abomasal infusions (67 g/d total FA) of 1) n-6 FA blend (N6) to provide approximately 43 g/d 18:2n-6 and 8 g/d of 18:3n-3; or 2) n-3 FA blend (N3) providing 43 g/d 18:3n-3 and 8 g/d 18:2n-6. Treatments were dissolved in ethanol, and the daily dose for each treatment was divided into 4 equal infusions, occurring every 6 h. The treatment period lasted from d 1 to 20, and the carryover period lasted from d 21 to 40. Results are presented as FA contents within each of the 4 main plasma lipid fractions: cholesterol esters (CE), phospholipids (PL); triglycerides (TG), and plasma nonesterified fatty acids. Concentrations of individual lipid fractions in plasma were not quantified. Plasma CE and PL had the highest content of polyunsaturated FA (PUFA) during both the treatment and carryover periods. In plasma PL, N3 increased the contents of total n-3 FA (134%), 18:3n-3 (267%), and eicosapentaenoic acid (96.3%, 20:5n-3), and decreased total n-6 FA (8.14%) and 18:2n-6 (8.16%) from d 4 to 20 compared with N6. In plasma CE, N3 increased the contents of total n-3 FA (191%) from d 4 to 20, 18:3n-3 from d 2 to 20 (178%), and 20:5n-3 from d 6 to 20 (59.9%), while N3 decreased total n-6 FA from d 4 to 20 (11.2%) and 18:2n-6 from d 2 to 20 (10.5%) compared with N6. In addition, compared with N6, N3 decreased arachidonic acid (20:4n-6) at d 2 (45%) and from d 10 to 20 (14.7%) in PL and tended to decrease 20:4n-6 without interacting with time for CE. Phospholipids were the only lipid fraction with detectable levels of docosahexaenoic acid (22:3n-6) in all samples, but we did not observe differences between treatments. In plasma TG, N3 increased the contents of total n-3 FA (135%) and 18:3n-3 (146%) from d 4 to 20, increased 20:5n-3 from d 12 to 20 (89%), decreased or tended to decrease total n-6 FA content from d 6 and 8 (26.9%), and tended to decrease 18:2n-6 at d 8 compared with N6. A similar pattern was observed for plasma nonesterified fatty acids. We observed positive carryover effects for both N3 and N6 at different degrees in all lipid fractions, with N3 promoting more consistent outcomes and increasing total n-3 FA throughout the carryover period (from d 22 to 40) in both PL (52.8%) and CE (68.6%) compared with N6. It is important to emphasize that the higher magnitude responses observed for n-3 FA are also influenced by the content of n-3 FA being much lower than those of n-6 FA in all lipid fractions. While these data provide important and robust information, future research quantifying changes in concentrations of individual lipid fractions in plasma and the entry and exit rates of specific FA will further enhance our understanding. In conclusion, abomasally infusing N3 and N6 increased the contents of n-3 and n-6 FA, respectively, in all plasma lipid fractions. These responses were more evident in PL and CE. We also observed positive carryover effects in all lipid fractions, where N3 had more consistent outcomes than N6. Our results indicate that dairy cows have a robust mechanism to conserve essential FA, with a pronounced preference for n-3 FA.
PubMed: 38908699
DOI: 10.3168/jds.2024-24907 -
Molecules (Basel, Switzerland) May 2024There has been an increase in interest in the application of ω-3 PUFAs, especially EPA and DHA, in the development of various food products owing to their myriad health...
There has been an increase in interest in the application of ω-3 PUFAs, especially EPA and DHA, in the development of various food products owing to their myriad health benefits. However, most fish oils do not contain more than 30% combined levels of EPA and DHA. In this study, through the urea complexation procedure, the production of EPA and DHA concentrate in their free fatty acids (FFAs) form was achieved from an enzymatic oil extracted from common kilka ( caspia). To gain the maximum value of EPA and DHA, the response surface methodology (RSM), which is an effective tool to categorize the level of independent variables onto the responses of an experimental process, was also used. Different variables including the urea-fatty acids (FAs) ratio (in the range of 2-6, /), the temperature of crystallization (in the range of -24-8 °C), and the time of crystallization (in the range of 8-40 h) were investigated by response surface methodology (RSM) for maximizing the EPA and DHA contents. Following the model validation, the levels of the variables at which the maximum desirability function (0.907 score) was obtained for response variables were 5:1 (urea-FAs ratio), -9 °C (the temperature of crystallization), and 24 h (the time of crystallization). Under these optimal conditions, increases of 2.2 and 4.4 times in the EPA and DHA concentrations were observed, respectively, and an increase in the concentrations of EPA and DHA from 5.39 and 13.32% in the crude oil to 12.07 and 58.36% in the ω-3 PUFA concentrates were observed, respectively. These findings indicate that the urea complexation process is efficient at optimizated conditions.
Topics: Urea; Fatty Acids, Omega-3; Fish Oils; Docosahexaenoic Acids; Eicosapentaenoic Acid; Animals; Crystallization
PubMed: 38893305
DOI: 10.3390/molecules29112430 -
Cancers May 2024This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and... (Review)
Review
This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol synthesis. The key enzymes under scrutiny include GPAT and AGPAT. Additionally, as most AGPATs exhibit LPLAT activity, enzymes participating in the Lands cycle with similar functions are also covered. The review begins by discussing the properties of these enzymes, emphasizing their specificity in enzymatic reactions, notably the incorporation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid and docosahexaenoic acid (DHA) into phospholipids. The paper sheds light on the intricate involvement of these enzymes in various diseases, including obesity, insulin resistance, and cancer. To underscore the relevance of these enzymes in cancer processes, a bioinformatics analysis was conducted. The expression levels of the described enzymes were correlated with the overall survival of patients across 33 different types of cancer using the GEPIA portal. This review further explores the potential therapeutic implications of inhibiting these enzymes in the treatment of metabolic diseases and cancer. By elucidating the intricate enzymatic pathways involved in lipid synthesis and their impact on various pathological conditions, this paper contributes to a comprehensive understanding of these processes and their potential as therapeutic targets.
PubMed: 38893234
DOI: 10.3390/cancers16112115 -
Nutrients Jun 2024Tumor cells are characterized by a delicate balance between elevated oxidative stress and enhanced antioxidant capacity. This intricate equilibrium, maintained within a...
Tumor cells are characterized by a delicate balance between elevated oxidative stress and enhanced antioxidant capacity. This intricate equilibrium, maintained within a threshold known as redox homeostasis, offers a unique perspective for cancer treatment by modulating reactive oxygen species (ROS) levels beyond cellular tolerability, thereby disrupting this balance. However, currently used chemotherapy drugs require larger doses to increase ROS levels beyond the redox homeostasis threshold, which may cause serious side effects. How to disrupt redox homeostasis in cancer cells more effectively remains a challenge. In this study, we found that sodium selenite and docosahexaenoic acid (DHA), a polyunsaturated fatty acid extracted from marine fish, synergistically induced cytotoxic effects in colorectal cancer (CRC) cells. Physiological doses of DHA simultaneously upregulated oxidation and antioxidant levels within the threshold range without affecting cell viability. However, it rendered the cells more susceptible to reaching the upper limit of the threshold of redox homeostasis, facilitating the elevation of ROS levels beyond the threshold by combining with low doses of sodium selenite, thereby disrupting redox homeostasis and inducing MAPK-mediated paraptosis. This study highlights the synergistic anticancer effects of sodium selenite and DHA, which induce paraptosis by disrupting redox homeostasis in tumor cells. These findings offer a novel strategy for more targeted and less toxic cancer therapies for colorectal cancer treatment.
Topics: Docosahexaenoic Acids; Colorectal Neoplasms; Sodium Selenite; Humans; Oxidation-Reduction; Homeostasis; Reactive Oxygen Species; MAP Kinase Signaling System; Cell Line, Tumor; Oxidative Stress; Cell Survival; Antioxidants; Drug Synergism; Antineoplastic Agents; Paraptosis
PubMed: 38892670
DOI: 10.3390/nu16111737 -
Impact of Resolvin-E1 and Maresin-1 on Bone Marrow Stem Cell Osteogenesis under Inflammatory Stress.Cells May 2024Periodontal disease is characterized by inflammation and bone loss. Central to its pathogenesis is the dysregulated inflammatory response, complicating regenerative...
Periodontal disease is characterized by inflammation and bone loss. Central to its pathogenesis is the dysregulated inflammatory response, complicating regenerative therapies. Mesenchymal stem cells (MSCs) hold significant promise in tissue repair and regeneration. This study investigated the effects of specialized pro-resolving mediators (SPMs), Resolvin E1 (RvE1) and Maresin 1 (MaR1), on the osteogenic differentiation of human bone marrow-derived MSCs under inflammatory conditions. The stem cells were treated with SPMs in the presence of lipopolysaccharide (LPS) to simulate an inflammatory environment. Osteogenic differentiation was assessed through alkaline phosphatase activity and alizarin red staining. Proteomic analysis was conducted to characterize the protein expression profile changes, focusing on proteins related to osteogenesis and osteoclastogenesis. Treatment with RvE1 and MaR1, both individually and in combination, significantly enhanced calcified deposit formation. Proteomic analysis revealed the differential expression of proteins associated with osteogenesis and osteoclastogenesis, highlighting the modulatory impact of SPMs on bone metabolism. RvE1 and MaR1 promote osteogenic differentiation of hBMMSCs in an inflammatory environment, with their combined application yielding synergistic effects. This study provides insights into the therapeutic potential of SPMs in enhancing bone regeneration, suggesting a promising avenue for developing regenerative therapies for periodontal disease and other conditions characterized by inflammation-induced bone loss.
Topics: Osteogenesis; Humans; Eicosapentaenoic Acid; Docosahexaenoic Acids; Mesenchymal Stem Cells; Cell Differentiation; Inflammation; Proteomics; Bone Marrow Cells; Lipopolysaccharides
PubMed: 38891064
DOI: 10.3390/cells13110932 -
Foods (Basel, Switzerland) May 2024The aim of this study was to optimize the formation of sodium caseinate (CS) and gum arabic (GA) complexes through the Maillard reaction and to evaluate their...
The aim of this study was to optimize the formation of sodium caseinate (CS) and gum arabic (GA) complexes through the Maillard reaction and to evaluate their effectiveness in improving the emulsification properties and stability of docosahexaenoic acid (DHA) nanoemulsions. First, the best target polysaccharides were selected, and the best modification conditions were determined using orthogonal experiments. Secondly, the response surface experiments were used to optimize the preparation process of the emulsion. The stability, in vitro digestion characteristics, and rheological characteristics of the emulsion prepared by means of CS-GA were compared with the emulsion prepared using a whey protein isolate (WPI). After the orthogonal test, the optimal modification conditions were determined to be a reaction time of 96 h, a CS-GA mass ratio of 1:2, a reaction temperature of 60 °C, and a degree of grafting of 44.91%. Changes in the infrared (IR), Raman, ultraviolet (UV), and endogenous fluorescence spectra also indicated that the complex structure was modified. The response surface test identified the optimal preparation process as follows: an emulsifier concentration of 5 g/L, an oil-phase concentration of 5 g/L, and a homogenization frequency of five, and the emulsion showed good stability. Therefore, the use of a nanoemulsion as a nanoscale DHA algal oil delivery system is very promising for extending the shelf life and improving the stability of food.
PubMed: 38890897
DOI: 10.3390/foods13111667 -
Foods (Basel, Switzerland) May 2024Edible crickets have recently been used as a new alternative protein source with high nutritional value. The nutritional and flavor-related value of edible crickets...
Edible crickets have recently been used as a new alternative protein source with high nutritional value. The nutritional and flavor-related value of edible crickets varies greatly depending on the species, growth conditions and processing conditions. However, few studies have investigated the effects of the diet fed to crickets during their growth phase on flavor. Therefore, in this study, we characterized the flavor-related factors of powder from crickets reared on apple by-products (ACP) by comparing them with those of powder from crickets reared on a control diet (CCP). The fatty acid composition and volatile compounds of each powder were determined using gas chromatography and mass spectrometry, followed by sensory analysis and color measurement. A decrease in unsaturated fatty acids, specifically γ-linolenic acid, α-linolenic acid, arachidonic acid and docosahexaenoic acid, was observed in ACP. A total of 50 volatile compounds were identified, of which 11 were present in only ACP, while 39 were found in both powders. The sensory analysis showed that the overall balance score of ACP was higher than that of CCP, and according to the color measurements, ACP was darker than CCP. These differences between CCP and ACP might have been due to the differences in the chemical composition of the diets fed to the crickets during their growth phase. The results of this study suggest that one of the factors determining the food value of edible crickets, especially in terms of flavor, is the diet they are fed during their growth phase.
PubMed: 38890896
DOI: 10.3390/foods13111668 -
The Journal of Nutritional Biochemistry Jun 2024Females have higher docosahexaenoic acid (DHA) levels than males, proposed to be a result of higher DHA synthesis rates from α-linolenic acid (ALA). However, DHA...
Females have higher docosahexaenoic acid (DHA) levels than males, proposed to be a result of higher DHA synthesis rates from α-linolenic acid (ALA). However, DHA synthesis rates are reported to be low, and have not been directly compared between sexes. Here, we apply a new compound specific isotope analysis model to determine n-3 PUFA synthesis rates in male and female mice and assess its potential translation to human populations. Male and female C57BL/6N mice were allocated to one of three 12-week dietary interventions with added ALA, eicosapentaenoic acid (EPA) or DHA. The diets included low carbon-13 (δC)-n-3 PUFA for 4 weeks, followed by high δC-n-3 PUFA for 8 weeks (n=4 per diet, time point, sex). Following the diet switch, blood and tissues were collected at multiple time points, and fatty acid levels and δC were determined and fit to one-phase exponential decay modeling. Hepatic DHA synthesis rates were not different (p>0.05) between sexes. However, n-3 docosapentaenoic acid (DPAn-3) synthesis from dietary EPA was 66% higher (p<0.05) in males compared to females, suggesting higher synthesis downstream of DPAn-3 of females. Estimates of percent conversion of dietary ALA to serum DHA was 0.2%, in line with previous rodent and human estimates, but severely underestimates percent dietary ALA conversion to whole body DHA of 9.5%. Taken together, our data indicates that reports of low human DHA synthesis rates may be inaccurate, with synthesis being much higher than previously believed. Future animal studies and translation of this model to humans are needed for greater understanding of n-3 PUFA synthesis and metabolism, and whether the higher-than-expected ALA-derived DHA can offset dietary DHA recommendations set by health agencies.
PubMed: 38876393
DOI: 10.1016/j.jnutbio.2024.109689 -
Frontiers in Nutrition 2024Polyunsaturated fatty acids (PUFAs) are essential nutrients that humans obtain from their diet, primarily through fish oil consumption. However, fish oil production is...
INTRODUCTION
Polyunsaturated fatty acids (PUFAs) are essential nutrients that humans obtain from their diet, primarily through fish oil consumption. However, fish oil production is no longer sustainable. An alternative approach is to produce PUFAs through marine microalgae. Despite the potential of algae strains to accumulate high concentrations of PUFAs, including essential fatty acids (EFAs), many aspects of PUFA production by microalgae remain unexplored and their current production outputs are frequently suboptimal.
METHODS
In this study, we optimized biomass and selected ω-3 PUFAs production in two strains of algae, AN-4 and CO3H. We examined a broad range of cultivation conditions, including pH, temperature, stirring intensity, nutrient concentrations, and their combinations.
RESULTS
We found that both strains grew well at low pH levels (4.5), which could reduce bacterial contamination and facilitate the use of industrial waste products as substrate supplements. Intensive stirring was necessary for rapid biomass accumulation but caused cell disruption during lipid accumulation. Docosahexaenoic acid (DHA) yield was independent of cultivation temperature within a range of 28-34°C. We also achieved high cell densities (up to 9 g/L) and stable DHA production (average around 0.1 g/L/d) under diverse conditions and nutrient concentrations, with minimal nutrients required for stable production including standard sea salt, glucose or glycerol, and yeast extract.
DISCUSSION
Our findings demonstrate the potential of strains to boost industrial-scale PUFA production and make it more economically viable. Additionally, these results may pave the way for smaller-scale production of essential fatty acids in a domestic setting. The development of a new minimal culturing medium with reduced ionic strength and antibacterial pH could further enhance the feasibility of this approach.
PubMed: 38854161
DOI: 10.3389/fnut.2024.1290701