Obesity and Hormonal Influences on Asthma: Mechanisms, Management Challenges, and Emerging Therapeutic Strategies.

Obesity and hormonal dysregulation, common comorbidities of asthma, not only influence asthma risk and onset but can also complicate its management. The pathobiological characteristics of obesity, such as insulin resistance and metabolism alterations, can impact lung function and airway inflammation while highlighting potential opportunities for therapeutic intervention. Likewise, obesity alters immune cell phenotypes and corticosteroid pharmacokinetics. Hormones such as sex hormones, incretins, and thyroid hormones can also affect asthma. This review highlights the mechanisms underlying obesity-related asthma and hormonal pathologies while exploring potential therapeutic strategies and the need for more research and innovative approaches in managing these comorbid conditions.

Comparative Evaluation of Effectiveness of Omega-3 Fatty Acids as an Adjunct to SRP with Conventional SRP: A Randomized Clinical Trial.

AIM: This study aims to compare the effectiveness of "omega-3 fatty acids" as an auxiliary to "scaling and root planing (SRP)" with traditional "scaling and root planing" in periodontal treatment in humans. MATERIALS AND METHODS: This study is a randomized control trial and was carried out over a period of 3 months (registered on 02/07/2023). Thirty patients were singled out according to the inclusion criteria, each having periodontitis (Stage II Grade B), and were arbitrarily distributed into two groups (control and test). The test group was treated with "scaling and root planing" along with the adjunctive application of "omega-3 fatty acids" while the control group was treated with "scaling and root planing" alone. Monthly follow-up was carried out over 90 days. Clinical parameters such as pocket probing depth (PPD), gingival index (GI), bleeding index (BI), and plaque index (PI) were measured respectively at baseline and 3 months. The data was recorded and statistically analyzed. RESULTS: The soft tissue architecture remained stable. The mean full mouth plaque index (FMPI) score was statistically significant (p < 0.001) when the control group was compared to the test group with a mean difference of 0.12 ± 0.02. The mean full mouth papillary bleeding index (FMPBI) score decreased at 3 months and was statistically significant compared to baseline with a mean difference of 0.24 ± 0.04 (p < 0.001). When the test group was compared with the control group, the FMGI was not significant (p = 0.02), with a mean difference of 0.16 ± 0.19. The PPD was not significant (p =1) when comparing both the groups, with a mean difference of 0 ± 0.66. Although the clinical parameters were statistically significant at 3 months when compared to baseline in both the groups, the FMGI and PPD were not significant. CONCLUSION: The combined action of using omega-3 fatty acid as an auxiliary to conventional scaling and root planing improved the periodontal parameters including both the soft and hard tissue outcomes. CLINICAL SIGNIFICANCE: The present study indicated that supplementary usage of omega-3 fatty acids is more beneficial for treating chronic and mild periodontitis than scaling and root planing alone. Omega-3 fatty acids can be used as energy for our cells, reduce the risk of blood clotting, maintain bone health, regulate metabolism, and reduce inflammation. Host modulatory therapy (HMT) with omega-3 fatty acids aims at reducing inflammation. With HMT as an adjunct, a better result of periodontal therapy was expected. It enhanced the positive effects on periodontal parameters and both the soft and hard tissue outcomes. How to cite this article: Salian S, Dhadse PV, Patil R, et al. Comparative Evaluation of Effectiveness of Omega-3 Fatty Acids as an Adjunct to SRP with Conventional SRP: A Randomized Clinical Trial. J Contemp Dent Pract 2024;25(5):440-444.

ω-3 PUFAs Ameliorated the Maternal High-Fructose Diet-Induced Early-Onset Retinopathy in Offspring via Inhibiting NLRP3-Associated Neuroinflammation.

SCOPE: Maternal high fructose diet (HFD) during pregnancy and lactation can initiate retinal dysfunction. However, the underlying mechanism remains largely unknown. METHODS AND RESULTS: By using the rodent model of maternal HFD in this study, the results from electroretinography (ERG) indicate that b-wave amplitude, an index of inner retinal function, is significantly reduced as early as 3 months old and the deteriorated effect can be detected at 15 months old. Further, the protein expressions of CD11b (a marker of active microglia), p40phox subunit of NADPH oxidase, GFAP (a marker of active astrocytes), and NLPR3 examined by western blot and immunofluorescence are significantly increased in the retina of the male HFD offspring at 3 months old. Treatment with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) for 2 weeks (from 2.5 to 3 months old) effectively reverses the aforementioned changes. CONCLUSION: Together, these results indicate that the early onset and extensive retinal dysfunction may be a result of glial activation which is induced by maternal HFD to initiate an inflammatory microenvironment leading to a long-term progression of retinopathy. Short-term administration of ω-3 PUFA at a young age may be a feasible strategy to intervene in the maternal HFD-programmed retinal impairment in male offspring.

Modification in mitochondrial function is associated with the FADS1 variant and its interaction with alpha-linolenic acid-enriched diet-An exploratory study.

Fatty acid desaturase (FADS1) variant-rs174550 strongly regulates polyunsaturated fatty acid (PUFA) biosynthesis. Additionally, the FADS1 is related to mitochondrial function. Thus, we investigated whether changes in mitochondrial function are associated with the genetic variation in FADS1 (rs174550) in human adipocytes isolated from individuals consuming diets enriched with either dietary alpha-linolenic (ALA) or linoleic acid (LA). Two cohorts of men homozygous for the genotype of FADS1 (rs174550) were studied: FADSDIET2 dietary intervention study with ALA- and LA-enriched diets and Kuopio Obesity Surgery study (KOBS), respectively. We could demonstrate that differentiated human adipose-derived stromal cells from subjects with the TT genotype had higher mitochondrial metabolism compared with subjects with the CC genotype of FADS1-rs174550 in the FADSDIET2. Responses to PUFA-enriched diets differed between the genotypes of FADS1-rs174550, showing that ALA, but not LA, -enriched diet stimulated mitochondrial metabolism more in subjects with the CC genotype when compared with subjects with the TT genotype. ALA, but not LA, proportion in plasma phospholipid fraction correlated positively with adipose tissue mitochondrial-DNA amount in subjects with the CC genotype of FADS1-rs174550 in the KOBS. These findings demonstrate that the FADS1-rs174550 is associated with modification in mitochondrial function in human adipocytes. Additionally, subjects with the CC genotype, when compared with the TT genotype, benefit more from the ALA-enriched diet, leading to enhanced energy metabolism in human adipocytes. Altogether, the FADS1-rs174550 could be a genetic marker to identify subjects who are most suitable to receive dietary PUFA supplementation, establishing also a personalized therapeutic strategy to improve mitochondrial function in metabolic diseases.

Oxidized polyunsaturated fatty acid promotes colitis and colitis-associated tumorigenesis in mice.

BACKGROUND AND AIMS: Human studies suggest that a high intake of polyunsaturated fatty acid (PUFA) is associated with an increased risk of inflammatory bowel disease (IBD). PUFA is highly prone to oxidation. To date, it is unclear whether unoxidized or oxidized PUFA is involved in the development of IBD. Here, we aim to compare the effects of unoxidized PUFA vs. oxidized PUFA on the development of IBD and associated colorectal cancer. METHODS: We evaluated the effects of unoxidized and oxidized PUFA on dextran sodium sulfate (DSS)- and IL-10 knockout-induced colitis, and azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice. Additionally, we studied the roles of gut microbiota and Toll-like receptor 4 (TLR4) signaling involved. RESULTS: Administration of a diet containing oxidized PUFA, at human consumption-relevant levels, increases the severity of colitis and exacerbates the development of colitis-associated colon tumorigenesis in mice. Conversely, a diet rich in unoxidized PUFA doesn't promote colitis. Furthermore, oxidized PUFA worsens colitis-associated intestinal barrier dysfunction and leads to increased bacterial translocation, and it fails to promote colitis in Toll-like receptor 4 (TLR4) knockout mice. Finally, oxidized PUFA alters the diversity and composition of gut microbiota, and it fails to promote colitis in mice lacking the microbiota. CONCLUSIONS: These results support that oxidized PUFA promotes the development of colitis and associated tumorigenesis in mouse models via TLR4- and gut microbiota-dependent mechanisms. Our findings highlight the potential need to update regulation policies and industrial standards for oxidized PUFA levels in food.

Lipid-Mediated Mechanisms of Thermal Adaptation and Thermoregulatory Behavior in Animals.

Temperature affects a variety of cellular processes because the molecular motion of cellular constituents and the rate of biochemical reactions are sensitive to temperature changes. Thus, the adaptation to temperature is necessary to maintain cellular functions during temperature fluctuation, particularly in poikilothermic organisms. For a wide range of organisms, cellular lipid molecules play a pivotal role during thermal adaptation. Temperature changes affect the physicochemical properties of lipid molecules, resulting in the alteration of cell membrane-related functions and energy metabolism. Since the chemical structures of lipid molecules determine their physicochemical properties and cellular functions, cellular lipids, particularly fatty acid-containing lipid molecules, are remodeled as a thermal adaptation response to compensate for the effects of temperature change. In this chapter, we first introduce the structure and biosynthetic pathway of fatty acid-containing lipid molecules, such as phospholipid and triacylglycerol, followed by a description of the cellular lipid-mediated mechanisms of thermal adaptation and thermoregulatory behavior in animals.

Association of open skill exercise and long-chain polyunsaturated fatty acid intake with brain volume changes among older community-dwelling Japanese individuals.

Considering that a multifactorial lifestyle approach may prove more effective than a single factor approach to improve or maintain brain health, we evaluated the association of exercise (open skill exercise [OSE] or closed skill exercise [CSE]) combined with long-chain polyunsaturated fatty acid (LCPUFAs) (docosahexaenoic acid [C22:6n-3, DHA], eicosapentaenoic acid [C20:5n-3, EPA], and arachidonic acid [C20:4n-6, ARA]) intake with brain atrophy among older Japanese individuals (n = 795, aged 60-88 years) without a self-reported history of dementia based on the datasets of a two-year longitudinal study. Brain volumes were measured using three-dimensional T1-weighted brain magnetic resonance imaging for follow-up periods of two years. The associations between multivariate-adjusted changes in brain volumes and OSE or CSE frequency (≥ once/month and < once/month) along with LCPUFA intake (≥ median and < median) at the baseline were assessed using a general linear model. Subgroup analysis was performed by restricting DHA and EPA intakes (n = 263; median, 323 mg/d), which represented levels similar to those in countries with low fish consumption. Higher OSE frequencies, ARA intakes, and their combination were inversely associated with decreases in total gray matter and frontal cortex volumes. In subgroup analysis, a combination of higher OSE frequencies and DHA intakes was also associated with a smaller decrease in total gray matter volume. Overall, our findings suggest that regular OSE engagement and appropriate LCPUFA intake may contribute to preventing brain volume decreases in older individuals.

Pericyte-to-Endothelial Cell Communication via Tunneling Nanotubes Is Disrupted by a Diol of Docosahexaenoic Acid.

The pericyte coverage of microvessels is altered in metabolic diseases, but the mechanisms regulating pericyte-endothelial cell communication remain unclear. This study investigated the formation and function of pericyte tunneling nanotubes (TNTs) and their impact on endothelial cell metabolism. TNTs were analyzed in vitro in retinas and co-cultures of pericytes and endothelial cells. Using mass spectrometry, the influence of pericytes on endothelial cell metabolism was examined. TNTs were present in the murine retina, and although diabetes was associated with a decrease in pericyte coverage, TNTs were longer. In vitro, pericytes formed TNTs in the presence of PDGF, extending toward endothelial cells and facilitating mitochondrial transport from pericytes to endothelial cells. In experiments with mitochondria-depleted endothelial cells displaying defective TCA cycle metabolism, pericytes restored the mitochondrial network and metabolism. 19,20-Dihydroxydocosapentaenoic acid (19,20-DHDP), known to disrupt pericyte-endothelial cell junctions, prevented TNT formation and metabolic rescue in mitochondria-depleted endothelial cells. 19,20-DHDP also caused significant changes in the protein composition of pericyte-endothelial cell junctions and involved pathways related to phosphatidylinositol 3-kinase, PDGF receptor, and RhoA signaling. Pericyte TNTs contact endothelial cells and support mitochondrial transfer, influencing metabolism. This protective mechanism is disrupted by 19,20-DHDP, a fatty acid mediator linked to diabetic retinopathy.

Impact of Methylated Cyclodextrin KLEPTOSE® CRYSMEB on Inflammatory Responses in Human In Vitro Models.

KLEPTOSE® CRYSMEB methylated cyclodextrin derivative displays less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases, linked in part to cholesterol complexation and immune response, however, its impact on inflammatory cascade pathways is not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells under physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® panel. Finally, its anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects that were driven by the inhibition of pro-inflammatory cytokine secretion and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Additionally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by other well-known anti-inflammatory molecules. Finally, KLEPTOSE® CRYSMEB may have an anti-inflammatory impact, which could be due to its effect on receptors such as TLR or direct complexation with LPS or PGE2, and conversely, this methylated cyclodextrin could stimulate a pro-inflammatory response involving lipid mediators and on proteins involved in communication with immune cells, probably via interaction with membrane cholesterol.

Group X phospholipase A2 links colonic lipid homeostasis to systemic metabolism via host-microbiota interaction.

The gut microbiota influences physiological functions of the host, ranging from the maintenance of local gut homeostasis to systemic immunity and metabolism. Secreted phospholipase A2 group X (sPLA2-X) is abundantly expressed in colonic epithelial cells but is barely detectable in metabolic and immune tissues. Despite this distribution, sPLA2-X-deficient (Pla2g10-/-) mice displayed variable obesity-related phenotypes that were abrogated after treatment with antibiotics or cohousing with Pla2g10+/+ mice, suggesting the involvement of the gut microbiota. Under housing conditions where Pla2g10-/- mice showed aggravation of diet-induced obesity and insulin resistance, they displayed increased colonic inflammation and epithelial damage, reduced production of polyunsaturated fatty acids (PUFAs) and lysophospholipids, decreased abundance of several Clostridium species, and reduced levels of short-chain fatty acids (SCFAs). These obesity-related phenotypes in Pla2g10-/- mice were reversed by dietary supplementation with ω3 PUFAs or SCFAs. Thus, colonic sPLA2-X orchestrates ω3 PUFA-SCFA interplay via modulation of the gut microbiota, thereby secondarily affecting systemic metabolism.

Plasma levels of EPA and DHA after ingestion of a single dose of EPA and DHA ethyl esters.

Omega-3 polyunsaturated fatty acids (n3 PUFA), specifically eicosapentaenoic acid (EPA, 20:5n3), and docosahexaenoic acid (DHA, 22:6n3), are essential for maintaining health. To better understand their biology, it is important to define their bioavailability. The aim of this cross-over study was to investigate and compare the acute effects on plasma EPA and DHA levels after single doses of EPA oil (99% pure) and DHA (97% pure) ethyl esters. Twelve men aged 20-40 years with a body-mass-index of 20-27 kg/m2 and low fish consumption were recruited. Several measures (e.g., 4-week run-in period, standardized diet, and blood collection protocols) were taken to reduce the inter-individual variability of plasma fatty acids levels. Using a cross-over design, the subjects received 2.2 g of EPA in the first test period and 2.3 g of DHA in the second. The test periods were separated by 2 weeks. Blood samples were taken before dosing and after 2, 4, 6, 8, 12, 24, 48, and 72 h. The mean ± SE maximum concentrations for EPA were higher than for DHA (115 ± 11 µg/mL vs. 86 ± 12 µg/mL; p = 0.05). The mean ± SE incremented area under the plasma concentration curve over 72 h for EPA (2461 ± 279 µg/mL) was 2.4 times higher (p < 0.001) than that for DHA (1021 ± 170 µg/mL). The mean ± SE half-life was for EPA and DHA was 45 ± 8 and 66 ± 12 h. Our results indicate that EPA administration in single doses leads to higher circulating plasma levels of EPA compared to an effect of an equivalent dose of DHA on DHA plasma levels.

Fatty acids and epigenetics in health and diseases.

Lipids are crucial for human health and reproduction and include diverse fatty acids (FAs), notably polyunsaturated FAs (PUFAs) and short-chain FAs (SCFAs) that are known for their health benefits. Bioactivities of PUFAs, including ω-6 and ω-3 FAs as well as SCFAs, have been widely studied in various tissues and diseases. Epigenetic regulation has been suggested as a significant mechanism affecting the progression of various diseases, including cancers and metabolic and inflammatory diseases. Epigenetics encompasses the reversible modulation of gene expression without altering the DNA sequence itself, mediated by mechanisms such as DNA methylation, histone acetylation, and chromatin remodeling. Bioactive FAs have been demonstrated to regulate gene expression via epigenetic modifications that are potentially important for modulating metabolic control and disease risk. This review paper discusses the evidence in support of bioactive FAs, including ω-6 and ω-3 FAs and SCFAs, eliciting various disease prevention via epigenetic regulation including methylation or acetylation.

Host cell-specific metabolism of linoleic acid controls Toxoplasma gondii growth in cell culture.

The obligate intracellular parasite Toxoplasma gondii can infect and replicate in any warm-blooded cell tested to date, but much of our knowledge about T. gondii cell biology comes from just one host cell type: human foreskin fibroblasts (HFFs). To expand our knowledge of host-parasite lipid interactions, we studied T. gondii in intestinal epithelial cells, the first site of host-parasite contact following oral infection and the exclusive site of parasite sexual development in feline hosts. We found that highly metabolic Caco-2 cells are permissive to T. gondii growth even when treated with high levels of linoleic acid (LA), a polyunsaturated fatty acid (PUFA) that kills parasites in HFFs. Caco-2 cells appear to sequester LA away from the parasite, preventing membrane disruptions and lipotoxicity that characterize LA-induced parasite death in HFFs. Our work is an important step toward understanding host-parasite interactions in feline intestinal epithelial cells, an understudied but important cell type in the T. gondii life cycle.

Nonlinear relationships of circulating polyunsaturated fatty acids with the complications of liver cirrhosis: A prospective, longitudinal cohort study.

BACKGROUND & AIMS: The role of circulating polyunsaturated fatty acids (PUFAs) in preventing liver cirrhosis complications remains unclear. METHODS: Between 2006 and 2010, 273,834 UK Biobank participants with plasma PUFA quantification data were enrolled and followed up until October 31, 2022. Plasma PUFAs were quantified using a high-throughput nuclear magnetic resonance-based metabolic profiling platform. Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma. RESULTS: During a median follow-up of 13.9 years, 2026 participants developed liver cirrhosis complications. Total plasma PUFAs, omega-3 PUFAs, docosahexaenoic acid (DHA), omega-6 PUFAs, and linoleic acid (LA) were inversely associated with the risk of liver cirrhosis complications, whereas the plasma omega-6/omega-3 ratio was positively associated. Nonparametrically restricted cubic spline regression showed nonlinear associations of plasma PUFAs with liver cirrhosis complications. The inflection points were 4.78 mmol/L for total PUFAs, 0.73 mmol/L for omega-3 PUFAs, 0.25 mmol/L for DHA, 4.07 mmol/L for omega-6 PUFAs, and 2.99 mmol/L for LA. Plasma omega-3 PUFAs were negatively associated with the risk of liver cirrhosis complications when omega-3 PUFAs were <0.73 mmol/L (adjusted hazard ratio [HR], 0.11 [0.08-0.16]), whereas the association was inverted when omega-3 PUFAs were ≥0.73 mmol/L (adjusted HR, 1.87 [1.20-2.92]). CONCLUSIONS: The protective effect of plasma omega-3 PUFAs on liver cirrhosis complications is reversed after passing the corresponding inflection point, suggesting an optimal dietary omega-3 PUFA supplementation dose.

Association between a combination of cognitively stimulating leisure activities and long-chain polyunsaturated fatty acid intake on cognitive decline among community-dwelling older Japanese individuals.

Multifactorial lifestyle approaches could be more effective than a single factor for maintaining cognitive function. This study investigated the association of combining cognitively stimulating leisure activities (CSLAs), including puzzles, quizzes, and cognitive training games, with intake of long-chain polyunsaturated fatty acids (LCPUFAs), including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), on cognitive function in the older Japanese individuals without dementia. Participants were community-dwelling Japanese individuals without a self-reported history of dementia (n = 906, aged 60-88 years) from datasets of a 2-year longitudinal study (baseline: 2006-2008 and follow-up: 2008-2010). CSLA engagement and LCPUFA intake were divided into high and low groups according to frequency (≥once/week and

Eicosapentaenoic acid administration ameliorates the progression of liver fibrosis after laparoscopic Kasai portoenterostomy.

PURPOSE: Biliary atresia (BA) poses a persistent challenge characterized by ongoing liver inflammation and subsequent fibrosis even after the clearance of jaundice (COJ). This study aimed to evaluate the therapeutic potential of eicosapentaenoic acid (EPA) in alleviating liver inflammation and limiting fibrosis during the post-COJ phase of BA. METHODS: Among the BA patients undergoing laparoscopic Kasai portoenterostomy (lapKP) between December 2016 and October 2021, EPA (20-40 mg/kg/day) was administered orally to those whose parents consented. The study included patients from January 2014 to October 2021, classifying them into two groups: EPA-treated (Group E) and untreated (Group N). Their liver fibrosis and clinical course at 1 and 2 years post-lapKP were compared. RESULTS: Group E consisted of 25 patients, while Group N comprised 32 patients. Twenty-one patients in Group E and 25 patients in Group N achieved COJ (p = 0.74). Among jaundice-free patients at 1 and 2 years post-lapKP, Group E exhibited significantly lower M2BPGi levels and platelet counts, and Group E showed a significant reduction in Aminotransferase-to-Platelet Ratio Index (APRI) at 2 years post-lapKP. CONCLUSION: Although EPA administration did not improve COJ, it attenuated the progression of liver fibrosis during the 2 years following lapKP in jaundice-free patients. (200/200Words).

The efficacy and acceptability of anti-inflammatory omega-3 polyunsaturated fatty acid supplements in sepsis management: a network meta-analysis of randomized controlled trials.

Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22nd, 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention.

Omega-3 fatty acids effectively mitigate high-sensitivity C-reactive protein (hs-CRP) biomarker of inflammation in acute myocardial infarction patients: a randomized, double-blind, placebo-controlled clinical trial.

Myocardial infarction (MI) is considered an inflammatory disease and among the leading causes of death globally. An essential indicator of inflammation, high-sensitivity C-reactive protein (hs-CRP), is linked with the acute MI prognosis. We aimed to examine the impact of omega-3 polyunsaturated fatty acids (PUFAs) as an anti-inflammatory supplement on hs-CRP levels in acute MI patients. Sixty patients with acute MI participated in this randomized, placebo-controlled trial. For 30 days, patients were randomized to receive omega-3 PUFAs (2 g/day, N = 30) or placebo (N = 30) on top of guideline-directed medical therapy. An initial and endpoint measurement of hs-CRP was performed. We found that the hs-CRP levels in both omega-3 PUFAs and placebo groups remarkably decreased following 30 days of treatment (decreasing from 1.84 (2.3) and 1.3 (2.6) to 0.38 (0.54) and 0.63 (1.12) mg/dL, respectively; P < 0.001). Following the 30 days of treatment, the reducing impact of omega-3 PUFAs (↓ 1.54 (1.98) mg/dL) on hs-CRP was more robust than the placebo group (↓ 0.92 (1.57) mg/dL, P = 0.008). Furthermore, the WBC, cholesterol, LDL, and triglyceride levels were markedly decreased in omega-3 and placebo groups after 30 days of therapy (P < 0.001 for all). However, no remarkable differences were reported in the level of these parameters after 30 days of therapy between both studied groups. Our findings showed that omega-3 PUFAs decrease hs-CRP amounts in patients with acute MI. Omega-3 PUFA supplementation may be an appropriate candidate in patients with early-stage acute MI for inhibiting inflammation.

Eicosapentaenoic Acid Rescues Cav1.2-L-Type Ca2+ Channel Decline Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here, we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes in the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with an oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction in cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction in Cav1.2 L-type Ca2+ current, mRNA, and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3',5'-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2 and CREB mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2 and CREB mRNA expressions, which was reversed by an ROS scavenger. Our data suggest that EPA rescues cellular Cav1.2-Ca2+ channel decline caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

ELOVL5 and VLDLR synergistically affect n-3 PUFA deposition in eggs of different chicken breeds.

There was no significant difference in the composition and content of fatty acids in eggs among different breeds initially, but following the supplementation of flaxseed oil, Dwarf Layer were observed to deposit more n-3 polyunsaturated fatty acid (PUFA) in eggs. Currently, there is limited research on the mechanisms underlying the differences in egg composition among different breeds. Therefore, in this study, 150 twenty-four-wk-old hens of each breed, including the Dwarf Layer and White Leghorn, were fed either a basal diet or a diet supplemented with 2.5% flaxseed oil. After 28 d, eggs and liver samples were collected to determine fatty acid composition, and serum, liver, intestine, and follicles were collected for subsequent biochemical, intestinal morphology, and lipid metabolism-related genes expression analysis. Duodenal contents were collected for microbial analysis. The results showed that there was no significant difference in the content and deposition efficiency of total n-3 PUFA in the liver of the 2 breeds, but the content and deposition efficiency of total n-3 PUFA in the egg of Dwarf Layer were significantly higher than those of White Leghorn after feeding flaxseed oil. Flaxseed oil and breeds did not have significant effects on cholesterol (CHO), free fatty acids (NEFA), low-density lipoprotein (LDL), and estrogen (E2) levels. After feeding with flaxseed oil, the villus height and the villus-to-crypt ratio in both breeds were increased and duodenal crypt depth was decreased. The villus-to-crypt ratio (4.78 vs. 3.60) in the duodenum of Dwarf Layer was significantly higher than that in White Leghorn after feeding with flaxseed oil. Flaxseed oil can impact the gut microbiota in the duodenum and reduce the microbiota associated with fatty acid breakdown, such as Romboutsia, Subdolibranulum, Lachnochlostridium, and Clostridium. This may mean that less ALA can be decomposed and more ALA can be absorbed into the body. Additionally, after feeding flaxseed oil, the mRNA levels of elongation enzymes 5 (ELOVL5), fatty acid desaturase 1 (FADS1), and fatty acid transporter 1 (FATP1) in the liver of Dwarf Layer were significantly higher than those in White Leghorn, while the mRNA levels of peroxisome proliferator-activated receptor alpha (PPAR), carnitine palmitoyl transferase 1 (CPT1), Acyl CoA oxidase 1 (ACOX1), and Acyl-CoA synthetase (ACSL) were significantly lower than those in White Leghorn. The mRNA level of FABP1 in the duodenum of Dwarf Layer was significantly higher than that of White Leghorn, while the mRNA level of FATP1 was significantly lower than that of White Leghorn. The protein levels of ELOVL5 in the liver of Dwarf Layer and very low-density lipoprotein receptor (VLDLR) in the follicles were significantly higher than those of White Leghorn. In summary, after feeding flaxseed oil, the higher ratio of villus height to crypt depth in Dwarf Layer allows more α-linolenic acid (ALA) to be absorbed into the body. The higher mRNA expression of FADS1, ELOVL5, and FATP1, as well as the higher protein expression of ELOVL5 in the liver of Dwarf Layer enhance the conversion of ALA into DHA. The higher protein expression of VLDLR in follicles of Dwarf Layer allows more n-3 PUFA to deposit in the follicles. These combined factors contribute to the Dwarf Layer's ability to deposit higher levels of n-3 PUFA in eggs, as well as improving the deposition efficiency of n-3 PUFA.