Ratio Of Monounsaturated Fatty Acids Research Articles

Abstract PR-06: Dietary fats dictate pancreatic cancer fate via phospholipid saturation

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the US and is anticipated to become the second within the next decade. Epidemiologic studies support a strong link between high fat diet (HFD) consumption and increased PDAC risk, however, the translational relevance of diet research has been limited by inconsistencies in fat source and consumption across human populations and mouse studies. Therefore, whether and how specific dietary fatty acids drive cancer development is poorly understood. To address this gap in knowledge, we performed a diet screen, comprised of 12 isocaloric HFDs differing solely in fat source and representing the diversity of modern human fat consumption, in an oncogenic Kras-driven mouse model (KC: Kras LSL-G12D /+;Pdx1-Cre) that closely mimics the genetic and histologic features of human PDAC progression. Unexpectedly, we discovered that diets rich in oleic acid – a monounsaturated fatty acid (MUFA) typically associated with good health – enhanced pancreatic tumorigenesis. Furthermore, we observed a strong positive correlation between increased tumor burden and diets exhibiting a high ratio of MUFAs to polyunsaturated fatty acids (PUFAs), concordant with high MUFA to PUFA levels in the plasma and in pancreatic phospholipids. Membrane phospholipid incorporation of MUFAs (relative to PUFAs) suppresses lipid peroxidation and cell death via ferroptosis. Consistent with this, pancreata from mice fed a MUFA-rich diet showed decreased expression of genes involved in lipid peroxidation and reduced histologic evidence of lipid peroxidation end products compared to a PUFA-rich diets. Furthermore, primary acinar cells from mice fed high MUFA diets were resistant to cell death upon treatment with ferroptosis inhibitors. Conversely, diets rich in PUFAs increased PUFA incorporation into pancreatic phospholipids, activated transcriptional programs of lipid peroxidation, and intercepted Kras-driven tumor progression in vivo. Collectively, these data support a role for dietary fatty acids in molding the pancreatic phospholipid landscape, altering lipid peroxidation and ferroptosis sensitivity to dictate tumor fate. Citation Format: Christian F Ruiz, Xiangyu Ge, Rylee McDonnell, Daniel McQuaid, Jennifer Kaplan, Guangtao Li, Michael C Rudolph, Fred F Gorelick, John Wysolmerski, Daniel Canals, John D Haley, Matthew Rodeheffer, Mandar D Muzumdar. Dietary fats dictate pancreatic cancer fate via phospholipid saturation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-06.

Disorders of fatty acid metabolism and imbalance in the ratio of monounsaturated fatty acids promote the development of pulmonary fibrosis

ObjectiveAlthough some studies suggested that metabolic abnormalities may contribute to the development of pulmonary fibrosis, there are no studies that have reported a clear causal relationship between them, and the aim of this study was to explore the causal relationship between plasma metabolites and pulmonary fibrosis using Mendelian randomization (MR) combined with metabolomics analysis. MethodsFirstly, we explored the causal relationship between 1400 metabolites and pulmonary fibrosis using MR analysis, and detected plasma metabolites in mice with pulmonary fibrosis using metabolomics technology, thus validating the results of MR analysis. In addition, we again used MR to explore the causal relationship between the results of the differential metabolite KEGG in metabolomics and pulmonary fibrosis. ResultsA total of 52 metabolites were screened for association with pulmonary fibrosis in the MR analysis of 1400 plasma metabolites with pulmonary fibrosis, based on P < 0.05 for the IVW method, with consistent OR directions for all methods. Four of them were validated in the plasma of mice with pulmonary fibrosis, namely carnitine c18:2 levels (negative correlation), Glutamine degradant levels (positive correlation), Propionylcarnitine (c3) levels (negative correlation), carnitine to palmitoylcarnitine (c16) ratio (negative correlation). In addition, KEGG analysis of plasma differential metabolites revealed that the signaling pathway of biosynthetic of unsaturated fatty acids was most affected in mice with pulmonary fibrosis, and MR analysis showed that imbalance in the ratio of monounsaturated fatty acids was significantly associated with pulmonary fibrosis. ConclusionsOur study suggests that abnormal fatty acid levels due to reduced levels of carnitine-like metabolites, and an imbalance in the ratio of monounsaturated, promote the development of pulmonary fibrosis. This study reveals the marker metabolites and metabolic pathways affecting the development of pulmonary fibrosis to provide a basis for the development of new drugs for the treatment of pulmonary fibrosis.

Abstract PO1-13-08: Comparative analysis of stearoyl-CoA desaturase 1 expression and activity index in model cell lines of breast cancer subclasses

Abstract Introduction Due to the unique conditions of the tumor microenvironment, such as hypoxia, poor angiogenesis, and mitochondrial dysfunction, cancer cells face challenges in obtaining nutrients and energy supply. However, monounsaturated fatty acids have been identified as preferred substrates for energy generation and maintenance of cellular structures in cancer cells. These fatty acids can be obtained through de novo fatty acid synthesis. Stearoyl-CoA desaturase 1 (SCD1) is the primary enzyme involved in the biosynthesis of monounsaturated fatty acids from saturated fatty acids and is known to be upregulated in various malignancies, including breast cancer. This study aimed to assess the expression and activity index of SCD1 in well-characterized MCF-7, SK-BR3, and MDA-MB231 breast cancer cell lines, representing luminal A/B, HER2-enriched, and triple-negative subtypes, respectively. Methods The breast cancer cell lines were cultured in RPMI-1640 medium with 10% fetal bovine serum at 37°C, 5% CO2, and 95% humidity for 72 hours. After harvesting the cells, SCD1 expression was analyzed using real-time quantitative PCR, and the activity index was determined by measuring the ratio of monounsaturated fatty acids to saturated fatty acids using capillary gas-liquid chromatography. Results MCF-7 cell line showed a significantly higher SCD1 expression compared to MDA-MB231 (250-fold, p&amp;lt; 0.0001) and SK-BR3 (83-fold, p&amp;lt; 0.0001) cell lines. The activity index of SCD1 was significantly higher in both MCF-7 and MDA-MB231 cell lines with fold changes of 2.6 and 2.5, respectively, compared to SK-BR3 cell line (p=0.004 for both). Conclusion Cell model assays demonstrated that the luminal A/B and triple-negative subtypes showed a higher capacity to convert saturated fatty acids to monounsaturated fatty acids through SCD1 enzyme activity, indicating a different lipid metabolism profile in the HER2-enriched subtype. These new findings reveal differences in SCD1 expression and activity among breast cancer subclasses. They highlight vulnerabilities in metabolism and identify potential therapeutic targets with clinical implications for managing breast cancer. Citation Format: Hamid-Reza Feizi, Amir Mehdizadeh, Zohreh Sanaat, Khadijeh Abbasi, Frank Gieseler, Masoud Darabi. Comparative analysis of stearoyl-CoA desaturase 1 expression and activity index in model cell lines of breast cancer subclasses [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-08.

Associations of dietary factors with gastric cancer risk: insights from NHANES 2003-2016 and mendelian randomization analyses.

Background: Gastric cancer (GC) continues to be one of the leading causes of cancer-related deaths globally. Diet significantly influences the incidence and progression of GC. However, the relationship between dietary intake and GC is inconsistent. Methods: A study was conducted with adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2016 to investigate possible associations between 32 dietary factors and GC. To further detect potential causal relationships between these dietary factors and the risk of GC, a two-sample Mendelian randomization (MR) analysis was conducted. The primary method employed was the inverse variance weighted (IVW) analysis, and its results were further validated by four other methods. Results: Of the 35,098 participants surveyed, 20 had a history of GC. Based on the results of weighted logistic multivariate analysis, it was observed that there was a positive correlation between total fat intake [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.01-1.17), p = 0.03] and GC as well as negative association of dietary monounsaturated fatty acids (MUFAs) intake [OR = 0.83, 95% CI: (0.76-0.92), p < 0.001]. Further evaluations of the odds of GC across the quartiles of dietary MUFAs showed that the top quartile of total MUFA intake was associated with a lower likelihood of GC in three different models [model1: OR = 0.03, 95% CI: (0.00-0.25), p < 0.01; model2: OR = 0.04, 95% CI: (0.00-0.38), p = 0.01; model3: OR = 0.04, 95% CI: (0.00-0.40), p = 0.01]. For the MR analyses, genetic instruments were selected from the IEU Open GWAS project; IVW analysis showed that GC risk was not associated with MUFAs [OR = 0.82, 95% CI: (0.59-1.14), p = 0.23] or the ratio of MUFAs to total fatty acids [OR = 1.00, 95% CI: (0.75-1.35), p = 0.98]. Similar results were observed when using the other MR methods. Conclusion: The NHANES study revealed that consuming MUFAs was linked to a lower risk of GC, although the results of MR analyses do not provide evidence of a causal relationship. Additional research is therefore necessary to clarify these findings.

Lipidomics‐based study of lipid quality of fish by‐products: a case study of sea bass (Lateolabrax japonicus)

SummaryBy‐products of sea bass are a good source of lipids, among which viscera was the best lipid source containing 66% total lipids. Acid value, peroxide value (POV), p‐anisidine value (p‐AV), and conjugated diene value (CDV) were used to monitor oxidation. Visceral oil has a relatively higher level of POV, AV and CDV than head and belly. Radical production detected by ESR spectroscopy was also high in viscera. Fatty acid analysis showed that visceral oil of sea bass has a very high ratio of monounsaturated fatty acid, which includes oleic acid (C18:1n9), and palmitoleic acid (C16:1n9) accounting for 28.45% and 3.25% of total visceral oil and are rich in omega‐6 polyunsaturated fatty acids accounting for 34.78% of total lipids. Volatile compounds in visceral oil were low with flora and spicy oil wax aroma. Low amounts of aldehydes, ketones and alcohols indicated a low level of oxidation in the early stage of storage. ESR results indicated higher free radical level in visceral oil, which might result in the Inside‐Out quality deterioration.

Analyses of potential causal contributors to increased waist/hip ratio-associated cardiometabolic disease: A combined and sex-stratified Mendelian randomization study.

Increased waist/hip ratio (WHR) contributes to type 2 diabetes, fatty liver, dyslipidaemia, hypertension and coronary artery disease, with potential sex-differential effects. Postulated mediators include increased lipid flux, branched-chain amino acids, glycine and glycoprotein acetyl, but their relative contributions and sex-specific impact on WHR-associated cardiometabolic disease (CMD) are not established. We therefore undertook combined and sex-stratified Mendelian randomization (MR) to assess the relative causal contributions of these mediators to WHR-associated CMD using summary statistics from the largest genome-wide association studies in European ancestries. In sex-combined MR analyses, increased WHR significantly reduces high-density lipoprotein (beta = -0.416, SE = 0.029, p = 2.87E-47), increases triglyceride (beta = 0.431, SE = 0.029, p = 1.87E-50), type 2 diabetes (odds ratio = 2.747, SE = 0.09, p = 26E-23), coronary artery disease (odds ratio = 1.478, SE = 0.045, p = 6.96E-18), alanine transaminase (beta = 0.062, SE = 0.004, p = 6.88E-67), and systolic (beta = 0.134, SE = 0.022, p = 7.81E-10) and diastolic blood pressure (beta = 0.162, SE = 0.026, p = 5.38E-10). Adjustment for the mediators attenuated WHR's effects, but the associations remained significant with concordant results in females. In males, a similar pattern was seen, except after adjusting for the effect of the ratio of monounsaturated fatty acid to total free fatty acid, the potential causal effect of WHR was no longer significant: high-density lipoprotein (beta = -0.117, SE = 0.069, p = .09) and triglyceride (beta = 0.051, SE = 0.068, p = .459). MR suggests WHR increases the risk of CMD independent of these mediators, with the exception of dyslipidaemia in males, which is largely driven by the monounsaturated fatty acid to total free fatty acid ratio.

Unraveling the causal link: fatty acids and inflammatory bowel disease.

Previous observational studies have revealed the strong relationship between fatty acids (FA) and inflammatory bowel disease (IBD). Nonetheless, due to the inherent limitations of retrospective research, the causality between the two has not been clearly established. Genetic variants associated with the 17 FA indicators were derived from genome-wide association studies. Summary statistics for the discovery cohort and testing cohort for IBD, including ulcerative colitis (UC) and Crohn's disease (CD), were available from IIBDGC and FinnGen, respectively. Bidirectional MR analysis and sensitivity analysis with multiple measures were applied to comprehensively investigate the causal link between FA and IBD. Combining the results of various MR methods, the validation of testing cohort, and the merging of meta-analysis, we demonstrated that genetically predicted Omega-3 FA levels, Ratio of Omega-3 FA to total FA, Docosahexaenoic acid (DHA) levels, and Ratio of DHA to total FA reduced the risk of IBD, UC, and CD. Meanwhile, multivariate MR suggested that the risk effects of Omega-3 FA and DHA for UC and CD were mainly affected by Saturated FA and Monounsaturated fatty acid (MUFA). Furthermore, although there was the causal association between Ratio of MUFA to total FA as well as Ratio of Polyunsaturated fatty acid (PUFA) to MUFA and CD, sensitivity analysis prompted that the findings were not robust. None of the above results had a reverse causal effect. This MR investigation provided evidence of causality between diverse FA and IBD. These findings offered new insights into the treatment and prevention of IBD.

Effect of black spot infection on the chemical composition and comprehensive quality of pecan (Carya illinoinensis) kernel oil

Abstract Objectives The changes in the chemical composition of oil from pecan kernels following infection with black spot disease were evaluated to determine whether the disease affects the quality of the seed oil. The findings should provide theoretical support for developing the pecan industry and enhancing the risk resistance of the industry. Materials and Methods Oil samples from healthy and diseased pecan kernels were obtained using the squeezing method, and the bioactive substances and fatty acid composition of the two types of oil samples were compared. The degree of oxidation and deterioration of the diseased kernel oil was evaluated. Based on supervised orthogonal partial least squares–discriminant analysis, gray correlation analysis, and unsupervised factor analysis, a multivariate evaluation model was established to comprehensively score the quality of the two types of oils. Results The results showed that, compared with the healthy kernel oil, the contents of total polyphenols and flavonoids, as well as the peroxide and acid values, were significantly higher in the diseased kernel oil. The content of oleic acid, as well as the ratio of monounsaturated fatty acids to polyunsaturated acids, was also significantly higher in the diseased kernel oil. In addition, no aflatoxin was detected. Multivariate analysis revealed no significant difference in the quality of diseased kernel oil compared with that of healthy kernel oil. Conclusions Therefore, following infection, the pecan oil begins to oxidize, but this does not have a significant negative effect on the nutrients, suggesting that oil from diseased kernels has the potential to be further processed and sold as edible-grade vegetable oil.

Association between circulating unsaturated fatty acid and preeclampsia: a two-sample Mendelian randomization study

Objective In recent years, several studies have reported an association between unsaturated fatty acids (UFAs) and the risk of developing preeclampsia; however, its exact causal effect is unclear. This study assessed the causal association between circulating UFAs and preeclampsia. Methods A two-sample Mendelian randomization (MR) study using publicly available genome-wide association study (GWAS) summary data for circulating UFA s (N = 114,999) and preeclampsia (N = 118,291) was performed. Single nucleotide polymorphisms (SNPs) significantly associated with exposure was selected as instrumental variables (IVs). The inverse variance weighted (IVW) test was used as the primary method for estimating causality in MR analysis, while MR pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression methods were used to assess horizontal pleiotropy. Cochran’s Q test was used to evaluate heterogeneity among SNPs, and leave-one-out sensitivity analysis was used to determine the effect of individual SNPs on the results of the MR analysis. Bonferroni correction was used as a correction for multiple corrections. Results Two-sample MR analysis suggested that the ratio of monounsaturated fatty acids (MUFAs) to total fatty acids (OR 1.150, 95% CI 1.006–1.315, p = 0.041), the ratio of polyunsaturated fatty acids (PUFAs) to total fatty acids (OR 0.805, 95% CI 0.658–0.986, p = 0.036) and the ratio of PUFAs to MUFAs (OR 0.807, 95% CI 0.694–0.938, p = 0.005) were causally associated with preeclampsia. After Bonferroni correction, the causal association between the ratio of polyunsaturated to MUFAs and preeclampsia remained statistically different. Conclusions This MR analysis provides evidence for a genetic causal association between circulating UFAs and preeclampsia.

Associations of diet quality and food consumption with serum biomarkers for lipid and amino acid metabolism in Finnish children: the PANIC study.

To investigate the associations of overall diet quality and dietary factors with serum biomarkers for lipid and amino acid metabolism in a general population of children. We studied 194 girls and 209 boys aged 6-8years participating in the Physical Activity and Nutrition in Children study. Food consumption was assessed by 4-day food records and diet quality was quantified by the Finnish Children Healthy Eating Index (FCHEI). Fasting serum fatty acids, amino acids, apolipoproteins, as well as lipoprotein particle sizes were analyzed with high-throughput nuclear magnetic resonance spectroscopy. Data were analyzed using linear regression adjusted for age, sex, and body fat percentage. FCHEI was directly associated with the ratio of polyunsaturated (PUFA) to saturated fatty acids (SFA) (PUFA/SFA), the ratio of PUFA to monounsaturated fatty acids (MUFA) (PUFA/MUFA), the ratio of PUFA to total fatty acids (FA) (PUFA%), the ratio of omega-3-fatty acids to total FA (omega-3 FA%), and inversely associated with the ratio of MUFA to total FA (MUFA%), alanine, glycine, histidine and very-low density lipoprotein (VLDL) particle size. Consumption of vegetable oils and vegetable-oil-based margarine (≥ 60% fat) was directly associated with PUFA/SFA, PUFA/MUFA, PUFA%, the ratio of omega-6 FA to total FA (omega-6 FA%), and inversely associated with SFA, MUFA, SFA to total FA (SFA%), MUFA%, alanine and VLDL particle size. Consumption of high-fiber grain products directly associated with PUFA/SFA, PUFA/MUFA, omega-3 FA%, omega-6 FA%, PUFA% and inversely associated with SFA and SFA%. Fish consumption directly related to omega-3 FA and omega-3 FA%. Consumption of sugary products was directly associated with histidine and VLDL particle size. Vegetable, fruit, and berry consumption had direct associations with VLDL particle size and the ratio of apolipoprotein B to apolipoprotein A1. Consumption of low fat (< 1%) milk was directly associated with phenylalanine. A higher consumption of high-fat (≥ 1%) milk was associated with lower serum MUFA/SFA and higher SFA%. Sausage consumption was directly related to SFA% and histidine. Red meat consumption was inversely associated with glycine. Better diet quality, higher in intake of dietary sources of unsaturated fat and fiber, and lower in sugary product intake were associated with more favorable levels of serum biomarkers for lipid and amino acid metabolism independent of adiposity. ClinicalTrials.gov: NCT01803776, registered March 3, 2013.

Association of tobacco smoke exposure with metabolic profile from childhood to early adulthood: the Special Turku Coronary Risk Factor Intervention Project.

To investigate the associations between passive tobacco smoke exposure and daily smoking with a comprehensive metabolic profile, measured repeatedly from childhood to adulthood. Study cohort was derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP). Smoking status was obtained by questionnaire, while serum cotinine concentrations were measured using gas chromatography. Metabolic measures were quantified by nuclear magnetic resonance metabolomics at 9 (n = 539), 11 (n = 536), 13 (n = 525), 15 (n = 488), 17 (n = 455), and 19 (n = 409) years. Association of passive tobacco smoke exposure with metabolic profile compared participants who reported less-than-weekly smoking and had serum cotinine concentration <1 ng/mL (no exposure) with those whose cotinine concentration was ≥10 ng/mL (passive tobacco smoke exposure). Associations of daily smoking with metabolic profile in adolescence were analysed by comparing participants reporting daily smoking with those reporting no tobacco use and having serum cotinine concentrations <1 ng/mL. Passive tobacco smoke exposure was directly associated with the serum ratio of monounsaturated fatty acids to total fatty acids [β = 0.34 standard deviation (SD), (0.17-0.51), P < 0.0001] and inversely associated with the serum ratios of polyunsaturated fatty acids. Exposure to passive tobacco smoke was directly associated with very-low-density lipoprotein particle size [β = 0.28 SD, (0.12-0.45), P = 0.001] and inversely associated with HDL particle size {β = -0.21 SD, [-0.34 to -0.07], P = 0.003}. Daily smokers exhibited a similar metabolic profile to those exposed to passive tobacco smoke. These results persisted after adjusting for body mass index, STRIP study group allocation, dietary target score, pubertal status, and parental socio-economic status. Both passive and active tobacco smoke exposures during childhood and adolescence are detrimentally associated with circulating metabolic measures indicative of increased cardio-metabolic risk.

The effects of unsaturated fatty acids on psoriasis: A two-sample Mendelian randomization study.

Unsaturated fatty acids have been reported to be associated with the risk of psoriasis. However, the causal relationship between them remains unclear This study aimed to explore the causal relationship between unsaturated FAs and psoriasis. Firstly, we obtained genome-wide association study (GWAS) data for psoriasis from the FINNGEN database (number of cases = 4510, number of controls = 212,242) and different FA levels (number of samples = 114,999) from the IEU OpenGWAS Project. Secondly, the genetic correlation coefficient was calculated using linkage disequilibrium fractional regression. Thirdly, a two-sample Mendelian randomization (MR) analysis was performed using independent instrumental variables (p < 5 × 10-8) to determine the direction of randomization. Finally, expression quantitative trait loci (eQTL)-related analyses of common single nucleotide polymorphisms (SNPs) were carried out to explore the potential molecular mechanisms of unsaturated FAs affecting psoriasis. We found that an increase in the ratio of monounsaturated fatty acids (MUFAs) to total fatty acids could increase the risk of psoriasis (inverse-variance weighted [IVW], adjusted odds ratio [OR] = 1.175; adjusted 95% confidence interval [CI] = 1.045-1.321; adjusted p = .007). However, an increase in the ratio of polyunsaturated fatty acids (PUFAa) to total fatty acids could decrease the risk of psoriasis (IVW, adjusted OR = 0.754; adjusted 95% CI = 0.631-0.901; adjusted p = .002). Moreover, an increase in the ratio of PUFAs to MUFAs could decrease the risk of psoriasis (IVW, adjusted OR = 0.823; adjusted 95% CI = 0.715-0.948; adjusted p = .007). The heterogeneity of data was eliminated, and pleiotropy was not detected. There was no statistical difference in the MR analysis of other fatty acids indices with psoriasis. Further, no statistically significant evidence was found to verify a causal relationship between psoriasis and fatty acid levels in reverse MR. Functional enrichment analysis showed that these eQTL related to common SNPs were mainly involved in organic ion transport, choline metabolism, and the expression of key metabolic factors mediated by PKA, ChREBP, and PP2A. Our study indicated that the ratio of MUFAs to total fatty acids had a positive causal effect on psoriasis, while the ratio of PUFAs to total fatty acids and the ratio of PUFAs to MUFAs had a negative causal effect on psoriasis. Moreover, PKA-, PP2A-, and ChREBP-mediated activation of metabolic factors may play an important role in this process.

Stearoyl-CoA Desaturase 1 as a Therapeutic Biomarker: Focusing on Cancer Stem Cells.

The dysregulation of lipid metabolism and alterations in the ratio of monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs) have been implicated in cancer progression and stemness. Stearoyl-CoA desaturase 1 (SCD1), an enzyme involved in lipid desaturation, is crucial in regulating this ratio and has been identified as an important regulator of cancer cell survival and progression. SCD1 converts SFAs into MUFAs and is important for maintaining membrane fluidity, cellular signaling, and gene expression. Many malignancies, including cancer stem cells, have been reported to exhibit high expression of SCD1. Therefore, targeting SCD1 may provide a novel therapeutic strategy for cancer treatment. In addition, the involvement of SCD1 in cancer stem cells has been observed in various types of cancer. Some natural products have the potential to inhibit SCD1 expression/activity, thereby suppressing cancer cell survival and self-renewal activity.

Investigation of GhFAT Genes Related to Seed Oil Content and Fatty Acid Composition in Gossypium hirsutum L.

Fatty Acyl-ACP thioesterase (FAT) is a key enzyme controlling oil biosynthesis in plant seeds. FATs can be divided into two subfamilies, FATA and FATB according to their amino acid sequences and substrate specificity. The Upland cotton genome contains 20 GhFAT genes, amongst which 6 genes were of the GhFATA subfamily and 14 of the GhFATB subfamily. The 20 GhFAT genes are unevenly distributed on 14 chromosomes. The GhFATA genes have 5 or 7 exons and the GhFATB genes have 6 or 7 exons. All GhFAT proteins have the conserved Acyl-ACP_TE domain and PLN02370 super family, the typical characteristics of plant thioesterases. Analyses of the expression level of GhFATs and the compositions of fatty acid in 5–60 days-post-anthesis seeds showed that the ratio of saturated fatty acids to unsaturated fatty acids was consistent with the expression profile of GhFATB12, GhFATB3, and GhFATB10; the ratio of monounsaturated fatty acid to polyunsaturated fatty acids was consistent with the expression profile of GhFATA3. The oil contents of mature cottonseeds were positively correlated with the contents of palmitic acid and linolenic acid as well as seed vigor. These results provide essential information for further exploring the role(s) of the specific GhFATs in determining oil biosynthesis and cottonseed compositions.

Association of physical activity with metabolic profile from adolescence to adulthood.

Physical activity benefits cardiometabolic health, but little is known about its detailed links with serum lipoproteins, amino acids, and glucose metabolism at young age. We therefore studied the association of physical activity with a comprehensive metabolic profile measured repeatedly in adolescence. The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project. At ages 13, 15, 17, and 19 years, data on physical activity were collected by a questionnaire, and circulating metabolic measures were quantified by nuclear magnetic resonance metabolomics from repeatedly assessed serum samples (age 13: n=503, 15: n=472, 17: n=466, and 19: n=361). Leisure-time physical activity (LTPA;MET h/wk) was directly associated with concentrations of polyunsaturated fatty acids, and inversely with the ratio of monounsaturated fatty acids to total fatty acids (-0.006SD; [-0.008, -0.003]; p < 0.0001). LTPA was inversely associated with very-low-density lipoprotein (VLDL) particle concentration (-0.003SD; [-0.005, -0.001]; p=0.002) and VLDL particle size (-0.005SD; [-0.007, -0.003]; p < 0.0001). LTPA showed direct association with the particle concentration and size of high-density lipoprotein (HDL), and HDL cholesterol concentration (0.004SD; [0.002, 0.006]; p < 0.0001). Inverse associations of LTPA with triglyceride and total lipid concentrations in large to small sized VLDL subclasses were found. Weaker associations were seen for other metabolic measures including inverse associations with concentrations of lactate, isoleucine, glycoprotein acetylation, and a direct association with creatinine concentration. The results remained after adjusting for body mass index and proportions of energy intakes from macronutrients. Physical activity during adolescence is beneficially associated with the metabolic profile including novel markers. The results support recommendations on physical activity during adolescence to promote health and possibly reduce future disease risks.

Effects of replacing soybean meal with linseed meal in broiler diet on selected broilers’ blood parameters, meat chemical composition, fatty acid profiles, and sensory characteristics

The study was conducted with the objective of determining the effects of the dietary replacement of soybean meal with graded levels of linseed meal on selected blood parameters, meat composition, fatty acid profiles, and meat quality of broiler chickens. Cobb500 broilers were fed diets containing linseed meal at 0% (T1), 6.5% (T2), 13% (T3), 19.5 (T4), and 26% (T5), replacing 0% to 100% soybean meal in compound rations for 45 days. The experiment was conducted using a completely randomized design with five treatments, each replicated three times with 12 birds. Blood hematological indices were not affected (P&amp;gt;0.05) by treatment diets while among the blood biochemistry triglyceride and cholesterol concentrations in T1 were higher (P&amp;lt;0.05) than in T3, T4, and T5. Glucose was higher in T3, T4, and T5 than in T1 and T2 (P&amp;lt;0.01). The breast and thigh proximate composition for crude protein (CP), ether extract (EE), ash, carbohydrate, and gross energy were similar (P&amp;gt;0.05) among treatments. The sensory scores for breast and thigh meat samples were not different (P&amp;gt;0.05) among treatments. The palmitic acid content of breast and thigh meat was higher (P&amp;lt;0.05) in T1 and T2 than in the other treatments. Eliadic and stearic acid concentrations in thigh meat were greater (P&amp;lt;0.05) in T1, T2, and T3 than in T4 and T5. The oleic and linoleic acid contents of thigh meat were higher (P&amp;lt;0.05) in T2 and T3 than in the rest of the treatments. Breast linolenic acid was high (P&amp;lt;0.05) in T5 but similar in thigh meat. Total saturated fatty acid (SFA) showed a decreasing trend with an increasing level of linseed meal (LSM) in the ration. The ratio of monounsaturated fatty acid (MUFA) to SFA for breast and thigh was higher in T4 and T5 than in T1 and T2. Breast meat ratio of omega-6 (n-6) to omega-3 (n-3) showed a decreasing trend as the level of LSM replacement for soybean meal (SBM) in the ration increased. Generally, linseed meal replacement levels up to 26% in the broilers’ diet improves the essential fatty acid content of chicken meat without affecting the proximate composition and the chickens’ normal blood indices and does not alter meat sensory attributes.

Saturated Fatty Acids in Cell Membrane Lipids Induce Resistance to 5-Fluorouracil in Colorectal Cancer Cells.

Resistance to chemotherapy is a major obstacle for patients with unresectable colorectal cancer (CRC); however, the factors that induce chemoresistance have not been elucidated. Lipid composition influences neoplastic behaviour. Therefore, this study examined whether lipid composition affects sensitivity to chemotherapeutic agents in CRC. We performed a lipidomic analysis of a CRC xenograft-derived spheroid model to identify potential relationships between the lipid profile and chemoresistance to 5-fluorouracil (5-FU). Genetic and pharmacological modulation of lipid synthesis were also used in the HCT-116 and DLD-1 CRC cell lines to further characterize resistance to 5-FU. Our lipidomic profiling revealed that phospholipids with saturated fatty acids (SFAs) were more abundant in 5-FU-resistant spheroids. The importance of phospholipids containing SFA in chemoresistance was confirmed by showing that in HCT-116 and DLD-1 cells, genetic or pharmacological inactivation of stearoyl-CoA desaturase-1, a key enzyme that converts SFAs to monounsaturated fatty acids, increased the proportion of SFAs in membranous phospholipids and reduced cell membrane fluidity, and this ultimately resulted in resistance to 5-FU. These data suggest that the saturated to monounsaturated fatty acid ratio in cellular membranous phospholipids affects sensitivity to chemotherapeutic agents.

Contribution of amyloid and tau to cerebrospinal fluid fatty acid indices in preclinical and prodromal Alzheimer’s participants

AbstractBackgroundSince Aβ42 derives from membrane‐bound amyloid precursor protein (APP), we propose that membrane lipid composition may influence how APP is processed. Therefore, we aim to determine if fluctuations in fatty acid metabolism accompany amyloid and tau pathology.MethodUsing neuropsychology and ELISA‐based Aβ42/T‐tau measures in CSF, we classify five groups of elderly subjects: c ognitively h ealthy with n ormal Aβ 42/T‐ t au (CH‐NAT, n=36 ), cognitively healthy with pathological Aβ42/T‐tau (CH‐PAT, n=34), and MCI participants with normal or pathological Aβ42/T‐tau (MCI‐NAT, n= 26; MCI‐PAT, n=12), and Alzheimer’s (n=25). We determined the unesterified fatty acid (UFA) levels and the fatty acid composition of CSF nanoparticulate (NP) fraction and supernatant fluid (SF) using GC/MS. We calculated the chain length, unsaturation, and peroxidation indices and the ratio of monounsaturated fatty acid (C18:1, oleic acid) to saturated fatty acid (C18:0, stearic acid) designated the stearoyl‐CoA desaturase (SCD) index.ResultUnesterified chain length, unsaturation, peroxidation, and desaturase indices are higher MCI‐NAT/PAT than in AD. In the SF fraction, fatty acid indices are higher in the prodromal MCI‐PAT state than AD. To determine if SCD could account for differences in unsaturation, we quantified the primary SCD substrate (C18:0) and product (C18:1) in CSF fractions. We found that unesterified C18:0 was lower while C18:1 was higher in MCI‐NAT than the other clinical groups. These changes in C18:0 and C18:1 levels resulted in a higher desaturase index in MCI‐NAT (0.35± 0.15) than in CH‐PAT (0.26±0.16, adjusted p‐value (q) = 0.0230) and AD (0.16±0.11, q &lt; 0.0001). In the SF fraction, C18:0 levels are lower in MCI‐PAT than AD concomitant with a higher C18:1 in MCI‐PAT than AD. These fatty acid differences result in a significantly higher desaturase index in the prodromal MCI‐PAT (0.46±0.15) than in AD (0.28±0.11, q = 0.0067).ConclusionThese studies show an increase in the unsaturation and peroxidation indices in early AD that may result from enhanced brain desaturase activity. These data suggest that fatty acid indices are potential biomarkers of preclinical or prodromal AD. The increase in fatty acid indices followed by a decrease in dementia indicate a need for state or stage‐specific combinatorial preventive therapies.

Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study.

Background and Aim: Previous observational studies indicated that the serum albumin levels and circulating metabolites are associated with a high risk of venous thromboembolism (VTE). However, whether these observations reflect causality remained unclear. Hence, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal associations of serum albumin and circulating metabolites with the risk of VTE.Methods and Results: Summary statistics of genetic instruments proxying serum albumin, total protein, and common circulating metabolites were extracted from genome-wide association studies in the European ancestry. Summary-level results of age- and sex-adjusted estimates for associations of the instruments with VTE were derived from the FinnGen consortium. We used the inverse-variance weighted (IVW) method as the primary analysis for univariable MR. Sensitivity analyses were performed to detect horizontal pleiotropy and outliers. Genetically proxied high-serum albumin and total protein levels were suggestive protective factor of VTE, with odds ratio (OR) = 0.69 (CI 0.54–0.89, p = 4.7 × 10−3) and 0.76 (CI 0.61–0.95, p = 0.015), respectively. Genetically proxied low-monounsaturated fatty acids and the ratio of monounsaturated fatty acid to total fatty acid are causally associated with increased risk of VTE, with ORs = 0.89 (CI 0.80–0.99, p = 0.031) and 0.85 (CI 0.78–0.94, p = 9.92 × 10−4), respectively. There is no indication of causal associations between other circulating metabolites and the risk of VTE.Conclusions: Genetically liability to low-serum albumin and total protein levels, low proxied monounsaturated fatty acids (MUFAs) and the ratio of MUFAs to total fatty acids are associated with the higher risk of VTE.

Increasing dietary SFA:MUFA ratio with low levels of LC-PUFA affected lipid metabolism, tissue fatty acid profile and growth of juvenile California Yellowtail (Seriola dorsalis)

Lipids rich in saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) are among the alternative sources reported to maintain growth and tissue fatty acid composition and, in some cases, reducing the long-chain polyunsaturated fatty acids (LC-PUFA) requirements. The present works aims to investigate the effects of different SFA:MUFA ratios on growth performance, tissue fatty acid composition, and the expression of crucial genes involved in the lipid metabolism of juvenile California Yellowtail (Seriola lalandi) fed diets with increasing SFA:MUFA ratios (1.6, 1.8, and 2.0) with low LC-PUFA levels. After eight weeks, fish fed the control diet outperformed the experimental feeds with increasing SFA:MUFA ratio in terms of final weight, specific growth rate, and liver index. No differences were observed in survival, viscerosomatic index, and condition factor across dietary treatments. Whole-body, liver, and muscle tissues proximate composition was slightly affected by increasing the dietary SFA:MUFA ratio. In terms of fatty acid composition, whole-body, liver, and muscle tissues reflected the dietary fatty acid composition to most extent, except SFA (mainly 16:0) that was not proportionally deposited. LC-PUFA sparing effect was demonstrated at a low degree in this study, likely due to the low SFA:MUFA ratio or high content of dietary MUFA. Significant changes were observed in the expression of genes related to lipid metabolism. The ppara and igf1 expression were higher in fish fed the Control diet than those fed SFA:MUFA 1.6 diet. Whereas the fish from SFA:MUFA 1.6 group displayed higher cptla expression compared to fish from SFA:MUFA 2.0.