Chain Saturated Fatty Acids Research Articles

The Spinocerebellar Ataxia 34-Causing W246G ELOVL4 Mutation Does Not Alter Cerebellar Neuron Populations in a Rat Model.

Spinocerebellar ataxia 34 (SCA34) is an autosomal dominant disease that arises from point mutations in the fatty acid elongase, Elongation of Very Long Chain Fatty Acids 4 (ELOVL4), which is essential for the synthesis of Very Long Chain-Saturated Fatty Acids (VLC-SFA) and Very Long Chain-Polyunsaturated Fatty Acids (VLC-PUFA) (28-34 carbons long). SCA34 is considered a neurodegenerative disease. However, a novel rat model of SCA34 (SCA34-KI rat) with knock-in of the W246G ELOVL4 mutation that causes human SCA34 shows early motor impairment and aberrant synaptic transmission and plasticity without overt neurodegeneration. ELOVL4 is expressed in neurogenic regions of the developing brain, is implicated in cell cycle regulation, and ELOVL4 mutations that cause neuroichthyosis lead to developmental brain malformation, suggesting that aberrant neuron generation due to ELOVL4 mutations might contribute to SCA34. To test whether W246G ELOVL4 altered neuronal generation or survival in the cerebellum, we compared the numbers of Purkinje cells, unipolar brush cells, molecular layer interneurons, granule and displaced granule cells in the cerebellum of wildtype, heterozygous, and homozygous SCA34-KI rats at four months of age, when motor impairment is already present. An unbiased, semi-automated method based on Cellpose 2.0 and ImageJ was used to quantify neuronal populations in cerebellar sections immunolabeled for known neuron-specific markers. Neuronal populations and cortical structure were unaffected by the W246G ELOVL4 mutation by four months of age, a time when synaptic and motor dysfunction are already present, suggesting that SCA34 pathology originates from synaptic dysfunction due to VLC-SFA deficiency, rather than aberrant neuronal production or neurodegeneration.

Anti-Inflammatory Effect of Dietary Pentadecanoic Fatty Acid Supplementation on Inflammatory Bowel Disease in SAMP1/YitFc Mice.

Dietary fats have been linked to the increasing incidence of chronic diseases, including inflammatory bowel diseases (IBD), namely, Crohn's disease (CD). This study investigated the impact of pentadecanoic acid (C15:0), a type of an odd-numbered chain saturated fatty acid, for its potential anti-inflammatory properties in different mouse models of experimental IBD using the SAMP1/YitFc (SAMP) mouse line (14- or 24-week-old), including chronic ileitis and DSS-induced colitis. To quantitively assess the effect of C:15, we tested two dosages of C:15 in selected experiments in comparison to control mice. Intestinal inflammation and intestinal permeability were used as primary outcomes. In ileitis, C:15 supplementation showed an anti-inflammatory effect in SAMP mice (e.g., a reduction in ileitis severity vs. control p < 0.0043), which was reproducible when mice were tested in the DSS model of colitis (e.g., reduced permeability vs. control p < 0.0006). Of relevance, even the short-term C:15 therapy prevented colitis in mice by maintaining body weight, decreasing inflammation, preserving gut integrity, and alleviating colitis signs. Collectively, the findings from both ileitis and colitis in SAMP mice indicate that C:15 may have therapeutic effects in the treatment of IBD (colitis in the short term). This promising effect has major translational potential for the alleviation of IBD in humans.

Influence of critical micelle concentration of choline-based long chain fatty acid soaps on their antibacterial activity against Methicillin resistant Staphylococcus aureus

HypothesisAntimicrobial resistance (AMR) is a pressing global health concern. ESKAPEE pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA) are notable of concern in healthcare settings due to their resistance to critical antibiotics. To combat AMR, the development of alternatives such as bacterial membrane-active agents is crucial. Fatty acids (FAs) have emerged as a sustainable, antibiotic-free solution with inherent antibacterial activity. However, long chain saturated fatty acids (LCFAs) sodium soaps exhibit poorly antibacterial properties in comparison to short chain FAs, believed to be linked to limited solubility in aqueous media. ExperimentsWe employed choline as a chaotropic organic counter-ion to enhance the solubility of LCFAs and investigated their antibacterial effects against MRSA. The optimal medium conditions for micelle formation for LCFAs was first investigated. Then, we determined the critical micelle concentration (CMC), micellar morphology, and aggregation number through surface tension measurements and small angle neutron scattering experiments. Antimicrobial activity was assessed using minimum bactericidal concentration (MBC) assays and time-kill experiments. FindingsWe have identified conditions where LCFAs are effective against MRSA for the first time, providing valuable insights for developing new antibacterial agents to fight AMR. LCFAs need to be used above their Krafft temperatures and CMC to exhibit antibacterial efficacy.

Using FT-IR as a fast method to measure fatty acid soaps in in vivo and in vitro digests.

The objective of the current study was to develop a simple method to measure fatty acid soaps, making use of FT-IR, representative for the soap formation observed in clinical trials. Calcium soaps have a unique coordination which leads to a typical double-splitting of the antisymmetric and symmetric carboxylate peaks. Absorbance values of these carboxylate peaks were used together with the absorbance of the hydrocarbon -CH2 antisymmetric and symmetric peaks to calculate the calcium soap absorbance. Based on the linear correlation between the calcium soap absorbance and the calcium soap concentration measured with GC-FID, a model was set-up and subsequently successfully validated to quantify calcium soap concentrations in faecal samples from clinical trials with this FT-IR method. With in vivo as well as in vitro digestion an inverse correlation between the long chain saturated fatty acid part of milk fat containing fat blends used for the infant formulas, and the formation of fatty acid soaps after digestion and defaecation could be observed. There is a clear link between the amount of long chain saturated fatty acids at the sn-1/3 position and their release as free fatty acid after lipolysis with the appearance of fatty acid soaps. These insights enable future development of fat blends for infant nutrition to optimize fatty acid soap formation and thereby gut discomfort in infants. These insights can be used to predict the soap formation capacity of a newly designed fat blend and thereby the improvement of infant nutrition products.

Plasma metabolomics identifies differing endotypes of recurrent wheezing in preschool children differentiated by symptoms and social disadvantage

Preschool children with recurrent wheezing are a heterogeneous population with many underlying biological pathways that contribute to clinical presentations. Although the morbidity of recurrent wheezing in preschool children is significant, biological studies in this population remain quite limited. To address this gap, this study performed untargeted plasma metabolomic analyses in 68 preschool children with recurrent wheezing to identify metabolomic endotypes of wheezing. K-means cluster analysis was performed on metabolomic dataset including a total of 1382 named and unnamed metabolites. We identified three metabolomic clusters which differed in symptom severity, exacerbation occurrence, and variables associated with social disadvantage. Metabolites that distinguished the clusters included those involved in fatty acid metabolism, fatty acids (long chain monounsaturated fatty acids, long chain polyunsaturated fatty acids, and long chain saturated fatty acids), lysophospholipids, phosphatidylcholines, and phosphatidylethanolamines. Pathway analyses identified pathways of interest in each cluster, including steroid metabolism, histidine metabolism, sphingomyelins, and sphingosines, among others. This study highlights the biologic complexity of recurrent wheezing in preschool children and offers novel metabolites and pathways that may be amenable to future study and intervention.

Dietary inclusion of insect oil: Impact on growth, nutrient utilisation, lipid metabolism, antioxidant and immune-related responses in European catfish (Silurus glanis L)

In this study, we investigated the black soldier fly (Hermetia illucens) larvae oil (IO) as replacement of fish oil and vegetable oil in the diets of European catfish. The formulated diets included a control diet (CTR) containing fish oil (FO) and rapeseed oil (RO), and two experimental diets replacing FO and RO, with 50% and 100% IO, respectively. The nutritional trial comprising 630 European catfish juveniles (average initial body weight: 28.1 ± 0.17 g) randomly distributed into triplicated dietary groups (CTR, IO50, and IO100) was conducted for 8 weeks in a recirculation aquaculture system. The study was focused to evaluate the impact of IO on fish growth and nutrient utilisation, lipid metabolism, antioxidant, and immune-related responses in juvenile fish. Results obtained indicated that all the diets promoted adequate fish growth and feed utilisation, with no significant differences in these parameters between the dietary fish groups. It appears that the diets did not impact the activity of digestive enzymes, but a decrease in the apparent digestibility coefficients was observed. Significant differences were observed in tissue fatty acid (FA) composition. The significantly higher levels of whole-body total saturated fatty acids and arachidonic acid in fish fed IO-based diets relative to those fed CTR diet were accompanied by significantly lower levels of whole-body monounsaturated fatty acids and n-3 polyunsaturated fatty acids (n-3 PUFA). However, some deviations in this trend were observed in the liver highlighting the sparing effect for long chain polyunsaturated fatty acids (LC-PUFAs). Gene expression analysis showed a significant upregulation of genes encoding lipoprotein lipase (lpl), carnitine palmitoyl transferase (cpt1a), and hepatocyte nuclear factor 4 alpha (hnf4α) in the livers of fish fed the IO100 diet. Among the five immune-related genes examined in the spleen, only interferon regulatory factor 1 was significantly upregulated in fish fed IO50 relative to the CTR. These results indicated upregulated metabolic activities in fish fed the IO100 diet probably due to a higher level of dietary medium chain saturated fatty acids (MCSFA) and a lower level of LC-PUFA, creating the need for fish to oxidise more MCSFA and to deposit more LC-PUFA in the tissues in order to maintain fatty acid balance.

Association of circulation very long chain saturated fatty acids with depression in NHANES 2011–2014

BackgroundRecent studies have shown that elevated levels of medium and long chain saturated fatty acids are associated with an increased risk of depression. However, little is known about the effect of very long chain saturated fatty acids (VLSFAs) on depression. Therefore, our study aimed to examine the association between VLSFAs and depression in the US adult population. MethodsA total of 2706 participants with serum VLSFAs detection from NHANES 2011–2014 were included in the study. Logistic regression models were used to evaluate the association between quartile levels of serum VLSFAs (20:0, 22:0, 23:0, 24:0, and total VLSFA) and depression. ResultsAfter adjusting for multiple variables, we found that increased circulating levels of 22:0, 23:0, 24:0 and total VLSFA were linearly associated with a reduced risk of depression (model 3, Q4 OR: 0.658, 95 % CI: 0.438–0.989, P-trend = 0.023; OR: 0.515, 95 % CI: 0.339–0.782, P-trend<0.001; OR: 0.556, 95 % CI: 0.370–0.835, P-trend = 0.003; OR: 0.652, 95 % CI: 0.435–0.976, P-trend = 0.021, respectively). Additionally, individuals with the highest serum ratios of 22:0/16:0, 23:0/16:0, 24:0/16:0 and total VLSFA/16:0 also had a lower risk of depression after adjusting for multiple variables compared to the group with the lowest serum VLSFAs/16:0 (P-trend = 0.001, <0.001, 0.001 and 0.004, respectively). Moreover, the decreasing trend of depression associated with increased VLSFAs/18:0 remained significant. ConclusionIn conclusion, our findings suggest that increased circulating levels of 22:0, 23:0, 24:0 and total VLSFA may have a protective effect against the risk of depression.

Elucidating the impact of sanitary waste on the formation of fat, oil and grease deposits in sewer systems

The accumulation of fat, oil and grease (FOG) deposits in sanitary sewer systems is a significant cause of sewer overflows, mainly due to their tendency to adhere to pipe walls. The aim of this study is to (i) develop laboratory-prepared FOG deposits using a mixture of iron (Fe) and aluminium (Al) metal ions, fatty acids, saccharides and cooked oils, in addition to various sanitary waste materials such as paper towels, wipes and pads and (ii) examine the characteristics of these FOG deposits. The goals of this study were to (i) gain a deeper understanding of the impact of sanitary waste on the formation of FOG deposits and (ii) discuss the detailed physiochemical properties of these FOG deposits. The findings revealed that FOG deposits can vary in nature, appearing as either a smooth, paste-like substance or a coarse, semi-solid material, depending on the types of waste present in the sewer. Analysis of the fatty acid profile indicated that the FOG deposits with wipes have the highest viscosity (3.2 × 104 Pa s) and larger composition of smaller chain saturated fatty acids (caprylic acid 0.64%, undecanoic acid 5.61%, lauric acid 4.65%, myristic acid 3.21% and palmitic 8.38%). In contrast, FOG deposits with Fe and Al metal impurities have higher heat resistance and thermal stability (melting point of 125 °C) and have larger composition of long chain fatty acids. Furthermore, FTIR analysis confirmed that these FOG deposits are composed of metallic salts of fatty acids, aligning with samples from sewer lines. Our results suggest that FOG deposit formation involves the aggregation of excess calcium, which compresses free fatty acid micelles, and a saponification reaction between the calcium aggregates and free fatty acids. This research illuminates the complex processes behind FOG deposit formation and their varied characteristics, providing valuable insights into potential strategies for preventing FOG-related sewer blockages.

Black Soldier Meal in Feed Could Adversely Affect Organic Broiler Meat Quality When Used for the Total or Half Replacement of Diet Proteins

Organic poultry sector needs high-quality proteins sources to meet specific requirements. The EU’s organic regulation forbids synthetic amino acids; therefore, soybean, with its balanced essential amino acid content, has become the most used protein source, though much of it is imported from non-EU countries, with sustainability and crop competition issues; therefore, it should be substituted with a high-protein-value alternative such as insect meal. In this study, 900 Aviagen Savanna broilers were fed with three different organic diets: soybean only (S100), 50% black soldier fly larvae meal (BSL) and 50% soybean (BSL50), and 100% BSL only (BSL100). Broiler performance, welfare, and fatty acids (FA) were analyzed. BSL50 and BSL100 negatively affected growth, while only BSL100 worsened all of the market-related performances. Meat showed a significant increase in saturated FA (SFA) (p &lt; 0.000) and a corresponding decrease in polyunsaturated FA (PUFA), in BSL50 and BSL100, but α-linolenic acid was not affected by BSL50 treatment (p &lt; 0.000). The SFA increase could represent a negative aspect for human health (e.g., cardiovascular diseases), but, as reported by other authors, medium chain SFA, (i.e., lauric acid), may show beneficial effects as well (i.e., antibacterial, anti-inflammatory and antioxidant properties).

Characterization of Three Types of Elongases from Different Fungi and Site-Directed Mutagenesis.

Fatty acid elongases play crucial roles in synthesizing long-chain polyunsaturated fatty acids. Identifying more efficient elongases is essential for enhancing oleaginous microorganisms to produce high yields of target products. We characterized three elongases that were identified with distinct specificities: McELO from Mucor circinelloides, PrELO from Phytophthora ramorum, and PsELO from Phytophthora sojae. Heterologous expression in Saccharomyces cerevisiae showed that McELO preferentially elongates C16 to C18 fatty acids, PrELO targets Δ6 polyunsaturated fatty acids, and PsELO uses long chain saturated fatty acids as substrates. McELO and PrELO exhibited more homology, potentially enabling fatty acid composition remodeling and enhanced LC-PUFAs production in oleaginous microorganisms. Site-directed mutagenesis of conserved amino acids across elongase types identified residues essential for activity, supported by molecular docking. Alanine substitution of conserved polar residues led to enzyme inactivation, underscoring their importance in the condensation reaction. Our findings offer promising elongase candidates for polyunsaturated fatty acid production, contributing to the bioindustry's sustainable development.

Circulating sphingolipids in relation to cognitive decline and incident dementia: The Cardiovascular Health Study.

Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain. We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (APOE) ε4 allele carriers). Cognitive decline was assessed annually across 6 years using modified Mini-Mental State Examination (3MSE) and Digital Symbol Substitution Test (DSST). Additionally, a subset of 3050 participants were followed for clinically adjudicated dementia. Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR]=1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR=1.26 [95% CI: 1.10-1.45]) were associated with higher risk of incident dementia. Several sphingolipid species appear to be involved in cognitive decline and dementia risk. Plasma levels of sphingolipids were associated with cognitive decline and dementia risk.Ceramides and sphingomyelins with palmitic acid were associated with faster annual cognitive decline and increased risk of dementia.The direction of association depended on the covalently bound saturated fatty acid chain length in analysis of cognitive decline.

Fatty Acid Profile of Snakehead (Channa striata) and Its By-Product by GC-MS

The increasing demand for sustainable and high-quality food sources has led to a growing interest in exploring alternative protein options. Fish-derived products, known for their nutritional value, unique flavor profiles, and potential health benefits, have gained significant attention. Among these, snakehead (Channa striata) and its by-products have emerged as promising resources for various food applications, including fish powder production. Fish powder holds immense potential in the food industry as a versatile ingredient, capable of enhancing nutritional content while minimizing waste. This research focuses on investigating the fatty acid composition and volatile compounds present in snakehead fish powder and its by-products. The study employs a combination of analytical techniques, namely gas chromatography-mass spectrometry (GC-MS) and lipid extraction methods, to identify and quantify fatty acids and volatile compounds in the fish powder samples, providing a comprehensive chemical profile. The data reveals variations in the fatty acid composition among different components of the snakehead powder samples, influenced by the fish's feeding habits. The presence of essential fatty acids, including omega-3 and omega-6, highlights the potential health benefits of consuming snakehead powder. Moreover, the identification of odd chain saturated fatty acids (OCS-FAs) in the samples indicates their potential contribution to human health. Notably, snakehead powder contains docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which have reported preventive effects on human coronary artery disease. In conclusion, snakehead powder is a valuable source of protein and essential fatty acids, with potential implications for human health. The study emphasizes the significance of incorporating polyunsaturated fatty acids (PUFAs) into the human diet, potentially through fish powder consumption. Overall, the findings highlight the potential benefits of snakehead meat, head, skin, and bone, encouraging the development of functional food products and their potential use in preventing stunting.

Comparison of Dietary Intakes and Fermented Food Consumption in Patients with and without Periodontal Disease

Lack of certain nutrients and foods in the diet may negatively affect oral health. Therefore, nutrition may play an important role in maintaining oral health. This study aimed to evaluate and compare the nutrient intakes, consumption of food groups and some fermented foods of individuals with periodontal disease and health. Thirty-one patients with periodontitis, 31 with gingivitis who applied to the periodontology clinic and 31 individuals of similar age and gender without periodontal disease were included in this study. Plaque, gingival indices, bleeding on probing, periodontal pocket depth, and clinical attachment level were evaluated. To determine individuals' daily energy, nutrient intakes, and consumption of food groups, 24-hour food consumption records were kept for three consecutive days by the nutritionist. Data on individuals' frequency and amount of consumption of some fermented products were recorded, considering the foods available in our culture and the market. Totally, 34 men and 59 women participated in the study. Mean energy intake was similar among groups. Energy from total dietary fat (%, P=0.042), saturated fatty acid (P=0.002), and short and medium chain fatty acids (P=0.003), consumption of dairy products (except cheese) (P=0.009), cheeses (P=0.025), coffee (P=0.036), whole-grain bread (P=0.010) and kefir (P=0.013) were different among individuals with periodontal disease and periodontal health. In conclusion, nutrition may have an impact on periodontal health and disease.

PM2.5-Bound Fatty Acids and Oxidative Potential: A Year-Round Study in Chiang Mai, Upper Northern Thailand

Air pollution study mostly targeted in components of fine particulate matter (PM2.5, particulate matter with aerodynamic diameter ≤ 2.5 µm) but their health implication is still scarce. Fatty acids could exhibit surfactant properties of PM2.5. We investigated the oxidative potential (OP) of PM2.5-bound fatty acids in Chiang Mai, upper northern Thailand: a year-round study in 2021. A dithiothreitol (DTT), an acellular assay, was used to evaluate the OP of eighty-nine PM2.5 filters collected from January to December 2021. A series of PM2.5-bound fatty acids i.e., C14:0–C30:0 fatty acids were determined by gas chromatography/mass spectrometry (GC/MS). Total fatty acids (C14:0–C30:0 and C18:1, C18:2) accounted for 498.7 ± 196.1 and 206.9 ± 112.8 ng/m³ in high biomass burning (HBB) and low biomass burning (LBB) periods, respectively. Mean values of OPDTTv (OP normalized by air volume of sampling) in HBB and LBB periods were 0.13 ± 0.06 and 0.03 ± 0.03 nmol/min/m³, respectively. Long chain saturated fatty acids (C22:0-26:0) mostly showed moderately significant correlation with OPDTTv (r = 0.33-0.47, P &lt; 0.01) in HBB period but showed no significant correlation in LBB period. Meanwhile, linoleic acid (C18:2) was the only individual compound among unsaturated fatty acids that significantly correlated with OPDTTv (r = 0.39, P &lt; 0.01). These findings suggest that PM2.5-bound fatty acids, particularly during open-biomass burning period, contribute to variations in oxidative potential, potentially influencing the health risks associated with PM2.5 exposure.

The plasma membrane of focal adhesions has a high content of cholesterol and phosphatidylcholine with saturated acyl chains.

Cellular functions, such as differentiation and migration, are regulated by the extracellular microenvironment, including the extracellular matrix (ECM). Cells adhere to ECM through focal adhesions (FAs) and sense the surrounding microenvironments. Although FA proteins have been actively investigated, little is known about the lipids in the plasma membrane at FAs. In this study, we examine the lipid composition at FAs with imaging and biochemical approaches. Using the cholesterol-specific probe D4 with total internal reflection fluorescence microscopy and super-resolution microscopy, we show an enrichment of cholesterol at FAs simultaneously with FA assembly. Furthermore, we establish a method to isolate the lipid from FA-rich fractions, and biochemical quantification of the lipids reveals that there is a higher content of cholesterol and phosphatidylcholine with saturated fatty acid chains in the lipids of the FA-rich fraction than in either the plasma membrane fraction or the whole-cell membrane. These results demonstrate that plasma membrane at FAs has a locally distinct lipid composition compared to the bulk plasma membrane.

A novel ELOVL4 variant, L168S, causes early childhood-onset Spinocerebellar ataxia-34 and retinal dysfunction: a case report

Spinocerebellar ataxia 34 (SCA34) is an autosomal dominant inherited disease characterized by age-related cerebellar degeneration and ataxia caused by mutations in the Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) gene. The ELOVL4 enzyme catalyzes the biosynthesis of both very long chain saturated fatty acids (VLC-SFA) and very long chain polyunsaturated fatty acids (VLC-PUFA) that are important for neuronal, reproductive, and skin function. Several variants in ELOVL4 have been shown to cause different tissue-specific disorders including SCA34 with or without Erythrokeratodermia Variabilis (EKV), a skin condition characterized by dry, scaly skin, Autosomal Dominant Stargardt-Like Macular Dystrophy (STGD3), and seizures associated with neuro-ichthyotic disorders. What is puzzling is how different mutations in the same gene seem to cause different tissue-specific disorders. To date, no SCA34 patients have presented with both SCA34 and STGD3 pathology that is caused by ELOVL4 variants that cause truncation of ELOVL4. Here, we report a novel case of an early childhood onset and rapidly progressive cerebellar degeneration and retinal dysfunction in a Belgian-Italian girl who developed severe dysarthria and gait problems starting at about 3.5 years of age and progressed to immobility by 4.5 years of age. Brain magnetic resonance imaging (MRI) revealed progressive vermian, cerebellar, cortical atrophy, progressive corpus callosum slimming, and hot cross bun sign visible on the MRI. Ophthalmological examinations also revealed progressive macular dysfunction as measured by electroretinography. Using exome sequencing, we identified a novel heterozygous ELOVL4 variant, c.503 T > C (p. L168S) in the patient. To understand the enzymatic function of this novel ELOVL4 variant and how it alters the levels of VLC-PUFA and VLC-SFA biosynthesis to contribute to cerebellar and retinal dysfunction, we expressed wild-type ELOVL4 or the L168S ELOVL4 variant in cell culture and supplemented the cultures with VLC-PUFA or VLC-SFA precursors. We showed that the L168S ELOVL4 variant is deficient in the biosynthesis of VLC-SFA and VLC-PUFA. Our work suggests that differential depletion of these fatty acids may be a contributing factor to the pathogenic mechanism of SCA34 with or without EKV. Further studies will help further define how the different ELOVL4 variants cause different tissue-specific disorders with variable ages of onset.

GPCR-mediated effects of fatty acids and bile acids on glucose homeostasis.

Fatty acids and glucose are key biomolecules that share several commonalities including serving as energy substrates and as signaling molecules. Fatty acids can be synthesized endogenously from intermediates of glucose catabolism via de-novo lipogenesis. Bile acids are synthesized endogenously in the liver from the biologically important lipid molecule, cholesterol. Evidence abounds that fatty acids and bile acids play direct and indirect roles in systemic glucose homeostasis. The tight control of plasma glucose levels during postprandial and fasted states is principally mediated by two pancreatic hormones, insulin and glucagon. Here, we summarize experimental studies on the endocrine effects of fatty acids and bile acids, with emphasis on their ability to regulate the release of key hormones that regulate glucose metabolism. We categorize the heterogenous family of fatty acids into short chain fatty acids (SCFAs), unsaturated, and saturated fatty acids, and highlight that along with bile acids, these biomolecules regulate glucose homeostasis by serving as endogenous ligands for specific G-protein coupled receptors (GPCRs). Activation of these GPCRs affects the release of incretin hormones by enteroendocrine cells and/or the secretion of insulin, glucagon, and somatostatin by pancreatic islets, all of which regulate systemic glucose homeostasis. We deduce that signaling induced by fatty acids and bile acids is necessary to maintain euglycemia to prevent metabolic diseases such as type-2 diabetes and related metabolic disorders.

Uji Aktivitas Antibakteri Virgin Coconut Oil (VCO) terhadap Pertumbuhan Bakteri Staphylococcus aureus

Infectious disease is a disease that is generally caused by infection with pathogenic microorganisms. Staphylococcus aureus is a bacterium that causes the most common infectious disease. S. aureus infects tissues or organs and can cause disease which has characteristic signs of inflammation, necrosis, and abscess formation. Generally treat this Staphylococcus aureus bacterial infection by administering antibiotics. Long-term administration of antibiotics can cause negative effects on the body. One of the efforts to control S. aureus bacterial infection is by using herbal ingredients. VCO contains medium chain saturated fatty acids (Medium Chain Fatty Acid). Medium Chain Fatty Acid, namely lauric acid which can be broken down into monolaurin which has antibacterial properties. This study aims to determine whether VCO can inhibit the growth of S. aureus bacteria. This research is a laboratory experiment using the paper disc diffusion method (Kirby-Bauer). The sample used is Staphylococcus aureus bacteria. The concentrations used in this study were 20%, 40%, 60%, 80%, 100% and amoxicillin positive control and DMSO negative control. Data analysis was performed statistically with the One-Way Analysis of Variance (ANOVA) test. Data is normally distributed and homogeneous. The results showed that the antibacterial activity of VCO was shown to have inhibition against S. aureus bacteria with an average concentration of 20% with a diameter of 14.4 mm (strong), 40% diameter 14.5 mm (strong), 60% diameter 14.6 mm (strong), 80% diameter 14.6 mm (strong), 100% diameter 16.0 mm (strong), positive control amoxicillin 7.9 mm and negative control 0 mm. The results of the ANOVA test showed a value of p = 0.000 (sig. &lt; 0.05) that there was a significant difference between all treatments with a positive control. It can be concluded that VCO was effective in inhibiting the growth of S. aureus bacteria, this was because the diameter of the VCO inhibition zone was larger than the positive control.

Profiling of branched chain and straight chain saturated fatty acids by ultra-high performance liquid chromatography-mass spectrometry

Branched chain fatty acids (BCFAs) are one of the important sub categories of fatty acids (FAs) which have unique functions in nature. They are commonly analyzed by GC–MS after derivatization to methyl esters (FAMEs). On the other hand, there is a lack of isomer-selective LC-MS methods which allow the distinction of different isomers with wide coverage of carbon chain length. In this work, a systematic retention and isomer selectivity study on seven commercially available UHPLC columns (six polysaccharide columns Chiralpak IA-U, IB-U, IC-U, ID-U, IG-U and IH-U; one Acquity UPLC CSH C18 column) was performed. Various experimental factors were evaluated including column temperatures, gradient profiles and flow rates to elucidate their effects on the separation ability of homologous series of BCFAs with distinct chain lengths, different branching types and branching positions. In general, IG-U outperformed the other columns in terms of isomer selectivity especially for the short and medium-chain BCFA isomers while RP C18 showed good potential in terms of selectivity for long-chain BCFA isomers. Furthermore, after the evaluation of the chromatographic retention pattern on the various columns and method optimization, we report a methodology for untargeted isomer-selective BCFA profiling without precolumn derivatization with UHPLC-ESI-MS/MS by quadrupole-time-of-flight instrument with SWATH acquisition. The best method provides selectivity for constitutional isomers of BCFAs covering distinct chain length (C5-C20) with different branching types (methyl or ethyl) and branching positions (2Me, 3Me, 4Me, 6Me, anteiso and iso-BCFAs) with an optimized LC condition on Acquity UPLC CSH C18 column. Finally, the optimized method was applied for the BCFAs profiling in lipid extracts of Staphylococcus aureus samples. Besides, pooled human platelets and pooled human plasma were evaluated as mammalian samples for presence of BCFAs as well. The new method showed strong potential for BCFA profiling in bacterial samples including different isomers anteiso and iso-BCFAs, which could be a useful tool for related subdisciplines in metabolomics and lipidomics in particular in combination with electron-activated dissociation MS. Compared to GC, the presented isomer selective LC methods can be also of great utility for preparative purposes. Equivalent (carbon) chain length numbers were calculated for RP18 and Chiralpak IG-U and compared to those of FAMEs obtained by GC.

Abstract P425: Diets Enriched in Stearate, Palmitate, and Oleate Differentially Modulate Gut Microbiome Composition in Post-Menopausal Women

Objective: Dietary stearic acid (18:0), a major saturated fatty acid (SFA) in Western diets, does not raise plasma LDL-C concentrations relative to other shorter chain SFAs (palmitic [16:0], myristic [14:0] and lauric [12:0]), and is associated with lower CVD risk. We investigated whether the cardioprotective effects of 18:0 and its metabolic product oleic acid (18:1, a monounsaturated fatty acid) relative to 16:0 is mediated via alterations in the gut microbiome. Methods: Twenty mildly hypercholesterolemic (LDL-C&gt;100mg/dL) post-menopausal women (50-85 years; BMI 25-35kg/m 2 ) consumed each of 3 isocaloric diets for 5 weeks according to a randomized controlled cross-over design. Diets provided 55%E carbohydrate, 15%E protein and 30%E fat with half of the fat provided by 16:0, 18:0 or 18:1, respectively. Fecal samples were collected at the end of each diet phase and shotgun metagenomic sequencing was performed. Alpha diversity (Shannon index, Simpson index and observed counts) was compared between diet groups using two-sample non-parametric tests. Beta-diversity was assessed using Bray-Curtis dissimilarity with PERMANOVA test. Differences in metagenomic features by diet group were evaluated using Partial Least Squares-Discriminant Analysis (PLS-DA) models of pairwise diet differences developed using the R package ‘mixOmics’. Results: No significant differences were observed in alpha and beta diversity between diet groups. However, the variability in microbial relative abundance was greater after participants consumed the 18:0 and 18:1 diets compared to the 16:0 diet. Specifically, mean relative abundance of Bacterioides dorei , Bacteroides vulgatus , and Ruminococcus were highest after participants consumed the 18:0 relative to the 16:0 diet and intermediate after the 18:1 diet. The relative abundance of Coprococcus , Parabacteroides distasonis , Coprobacillus and Blautia were higher after participants consumed the 18:1 relative to the 16:0 diet. These microbial species have been associated with several anti-inflammatory pathways and decreased bacterial lipopolysaccharide production. Conclusion: These data document modest but distinctive effects of dietary SFAs on gut microbiome composition and functionality, suggesting that the favorable effects of 18:0 and 18:1 relative to 16:0 on CVD risk factors could be mediated, in part, by the gut microbiome.