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Myriocin modulates the altered lipid metabolism and storage in cystic fibrosis.
Signorelli, P, Pivari, F, Barcella, M, Merelli, I, Zulueta, A, Dei Cas, M, Rosso, L, Ghidoni, R, Caretti, A, Paroni, R, et al
Cellular signalling. 2021;:109928
Abstract
Cystic fibrosis (CF) is a hereditary disease mostly related to ΔF508 CFTR mutation causing a proteinopathy that is characterized by multiple organ dysfunction, primarily lungs chronic inflammation, and infection. Defective autophagy and accumulation of the inflammatory lipid ceramide have been proposed as therapeutic targets. Accumulation of lipids and cholesterol was reported in the airways of CF patients, together with altered triglycerides and cholesterol levels in plasma, thus suggesting a disease-related dyslipidemia. Myriocin, an inhibitor of sphingolipids synthesis, significantly reduces inflammation and activates TFEB-induced response to stress, enhancing fatty acids oxidation and promoting autophagy. Myriocin ameliorates the response against microbial infection in CF models and patients' monocytes. Here we show that CF broncho-epithelial cells exhibit an altered distribution of intracellular lipids. We demonstrated that lipid accumulation is supported by an enhanced synthesis of fatty acids containing molecules and that Myriocin is able to reduce such accumulation. Moreover, Myriocin modulated the transcriptional profile of CF cells in order to restore autophagy, activate an anti-oxidative response, stimulate lipid metabolism and reduce lipid peroxidation. Moreover, lipid storage may be altered in CF cells, since we observed a reduced expression of lipid droplets related proteins named perilipin 3 and 5 and seipin. To note, Myriocin up-regulates the expression of genes that are involved in lipid droplets biosynthesis and maturation. We suggest that targeting sphingolipids de novo synthesis may counteract lipids accumulation by modulating CF altered transcriptional profile, thus restoring autophagy and lipid metabolism homeostasis.
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Total Dietary Fat Intake, Fat Quality, and Health Outcomes: A Scoping Review of Systematic Reviews of Prospective Studies.
Schwingshackl, L, Zähringer, J, Beyerbach, J, Werner, SS, Heseker, H, Koletzko, B, Meerpohl, JJ
Annals of nutrition & metabolism. 2021;(1):4-15
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INTRODUCTION We conducted a scoping review of systematic reviews (SRs) on dietary fat intake and health outcomes in human adults within the context of a position paper by the "International Union of Nutritional Sciences Task force on Dietary Fat Quality" tasked to summarize the available evidence and provide dietary recommendations. METHODS We systematically searched several databases for relevant SRs of randomized controlled trials (RCTs) and/or prospective cohort studies published between 2015 and 2019 assessing the association between dietary fat and health outcomes. RESULTS Fifty-nine SRs were included. The findings from SRs of prospective cohort studies, which frequently compare the highest versus lowest intake categories, found mainly no association of total fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) with risk of chronic diseases. SRs of RCTs applying substitution analyses indicate that SFA replacement with PUFA and/or MUFA improves blood lipids and glycemic control, with the effect of PUFA being more pronounced. A higher intake of total trans-fatty acid (TFA), but not ruminant TFA, was probably associated with an increased risk of mortality and cardiovascular disease based on existing SRs. CONCLUSION Overall, the available published evidence deems it reasonable to recommend replacement of SFA with MUFA and PUFA and avoidance of consumption of industrial TFA.
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Diffusible Signaling Factor, a Quorum-Sensing Molecule, Interferes with and Is Toxic Towards Bdellovibrio bacteriovorus 109J.
Dwidar, M, Jang, H, Sangwan, N, Mun, W, Im, H, Yoon, S, Choi, S, Nam, D, Mitchell, RJ
Microbial ecology. 2021;(2):347-356
Abstract
Bdellovibrio bacteriovorus 109J is a predatory bacterium which lives by predating on other Gram-negative bacteria to obtain the nutrients it needs for replication and survival. Here, we evaluated the effects two classes of bacterial signaling molecules (acyl homoserine lactones (AHLs) and diffusible signaling factor (DSF)) have on B. bacteriovorus 109J behavior and viability. While AHLs had a non-significant impact on predation rates, DSF considerably delayed predation and bdelloplast lysis. Subsequent experiments showed that 50 μM DSF also reduced the motility of attack-phase B. bacteriovorus 109J cells by 50% (38.2 ± 14.9 vs. 17 ± 8.9 μm/s). Transcriptomic analyses found that DSF caused genome-wide changes in B. bacteriovorus 109J gene expression patterns during both the attack and intraperiplasmic phases, including the significant downregulation of the flagellum assembly genes and numerous serine protease genes. While the former accounts for the reduced speeds observed, the latter was confirmed experimentally with 50 μM DSF completely blocking protease secretion from attack-phase cells. Additional experiments found that 30% of the total cellular ATP was released into the supernatant when B. bacteriovorus 109J was exposed to 200 μM DSF, implying that this QS molecule negatively impacts membrane integrity.
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Changes in fatty acid levels (saturated, monounsaturated and polyunsaturated) during pregnancy.
Aparicio, E, Martín-Grau, C, Hernández-Martinez, C, Voltas, N, Canals, J, Arija, V
BMC pregnancy and childbirth. 2021;(1):778
Abstract
BACKGROUND During pregnancy a high amount of fatty acids (FA) is necessary to meet foetus demands, which vary during gestation. The present study describes the changes in maternal fatty acid concentrations during pregnancy in a sample of pregnant women. METHODS This is a longitudinal study of 479 pregnant women who were monitored from the first trimester to third trimester of pregnancy. Data on maternal characteristics were recorded and a serum sample was collected in each trimester. The fatty acid profile (saturated (SFA: total, lauric acid, myristic acid, palmitic acid, stearic acid), monounsaturated (MUFA: total, palmitoleic acid, oleic acid) and polyunsaturated fatty acids (PUFA: total omega-6 (n-6), linoleic acid, dihomo-γ-linolenic acid, arachidonic acid (AA), total omega-3 (n-3), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)) was analysed with a gas chromatography-mass spectrometry combination. RESULTS From the first trimester to third trimester of pregnancy, a significant increase in total SFA, total MUFA and total n-6 PUFA was found. (p < 0.001). Nevertheless, the serum concentration of arachidonic acid (AA), eicosapentaenoic acid (EPA) and total n-3 PUFA decreased during gestation (p < 0.001). A statistically non-significant result was observed for the docosahexaenoic acid (DHA) serum concentration between the first and third trimesters of pregnancy. Significant correlations were observed between each total fatty acid concentrations of the first and third trimesters. CONCLUSION The circulating serum concentration of SFA, MUFA and n-6 PUFA increases during pregnancy, whereas essential fatty acids such as AA and EPA decrease, and DHA remains unchanged. Further research is necessary to understand the role played by FA throughout gestation.
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Effect of two different dietary fatty acid profiles and variant rs266729 in ADIPOQ on weight loss and adiponectin concentrations.
de Luis, DA, Primo, D, Izaola, O, Aller, R
Endocrinologia, diabetes y nutricion. 2020;(6):374-382
Abstract
BACKGROUND The role of ADIPOQ gene rs266729 variants on weight loss after a dietary intervention are still unclear. OBJECTIVE To analyze the effects of the ADIPOQ gene rs266729 variant n weight loss, cardiovascular risk factors, and adiponectin levels after two hypocaloric diets with different dietary fatty profiles. DESIGN A population of 362 obese patients was enrolled in a randomized clinical trial with two diets (Diet M, monounsaturated fat-enriched diet, and Diet P, polyunsaturated-fat enriched diet). Anthropometric measurements, an assessment of nutritional intake, and biochemical tests were performed at baseline and after 12 weeks. RESULTS Weight loss was similar with both diets. After Diet M, only subjects with CC genotype showed significant improvements in total cholesterol (CC vs. CG±GG) (-9.0±1.1mU/L vs. -4.5±2.4mg/dL, p=0.01), LDL cholesterol (-6.0±1.1mg/dL vs. -3.0±0.9mg/dL, p=0.03), glucose (-4.7±1.1mg/dL vs. -0.6±0.5mg/dL, p=0.01), and insulin levels (-2.6±1.0mU/L vs. -0.7±0.3mU/L, p=0.02) and in HOMA-IR (-0.5±0.2 units vs. -0.2±0.4 units, p=0.03). The same improvement was reported after Diet P in all parameters, including total cholesterol (CC vs. CG±GG) (-8.0±1.2mU/L vs. -2.1±1.4mg/dL, p=0.02), LDL cholesterol (-7.3±1.2mg/dL vs. -2.1±0.8mg/dL, p=0.02), glucose (-3.2±0.1mg/dL vs. -0.2±0.5mg/dL, p=0.01), and insulin levels (-2.5±1.0mU/L vs. -1±0.6mU/L, p=0.02) and HOMA-IR (-0.5±0.1 units vs. -0.3±0.4 units, p=0.02). Only subjects with CC genotype showed significant increases in adiponectin levels after both diets: (Diet M: 10.3±2.0ng/dL vs. Diet P: 9.3±2.9ng/dL, p=0.43). CONCLUSION The CC genotype of ADIPOQ gene rs266729 variant is associated to increased adiponectin levels and decreases in LDL cholesterol, glucose, insulin, and HOMA-IR levels after weight loss.
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Diabetes-specific formulas high in monounsaturated fatty acids and metabolic outcomes in patients with diabetes or hyperglycaemia. A systematic review and meta-analysis.
Sanz-París, A, Matía-Martín, P, Martín-Palmero, Á, Gómez-Candela, C, Camprubi Robles, M
Clinical nutrition (Edinburgh, Scotland). 2020;(11):3273-3282
Abstract
OBJECTIVE The aim of this study was to compare the metabolic benefits of diabetes-specific formulas (DSF) high in monounsaturated fatty acids (MUFA) with standard formulas (STDF) in adult patients with type 1, type 2 diabetes or stress-induced hyperglycaemia. RESEARCH DESIGN AND METHODS A systematic review and meta-analysis were conducted through a literature search using different electronic databases from the index date to December 2018. We included randomised controlled trials that assessed the health benefits of high MUFA DSF vs STDF. Included outcomes were glycaemic control, lipid metabolism and tolerance. Effect sizes were calculated as standardised mean differences (SMDs) (<0.4 were considered small, 0.4-0.7 moderate and >0.7 large). This systematic review was registered as CRD42018108931 on Prospero. RESULTS Of 385 references reviewed, 18 studies involving 845 adults met our inclusion criteria and contributed to the meta-analysis. Use of a high MUFA DSF compared with a STDF was associated with a statistically significant decrease in peak of postprandial glucose [SMD -1.53, 95% confidence interval (CI) -2.44 to -0.61], incremental glucose response (SMD -1.19, 95% CI -1.71 to -0.68), area under the curve of plasma insulin (SMD -0.65, 95% CI -1.03 to -0.26), mean blood glucose level (SMD -0.41, 95% CI -0.63 to -0.19), glycosylated haemoglobin (HbA1c) change (SMD -0.63, 95% CI -1.21 to -0.05), glucose variability (SMD -0.93, -1.55 to -0.31), mean administered insulin dose (SMD -0.49, 95% CI -0.85 to -0.14), mean blood triglycerides (SMD -0.34, 95% CI -0.65 to -0.03) and increase of mean blood high-density lipoproteins (SMD +0.42, 95% CI 0.08 to 0.76). Non-significant differences were found for tolerance [odds ratio (OR) 0.95, 95% CI 0.87 to 1.05]. CONCLUSIONS This meta-analysis shows that a DSF (oral supplements and tube feeds) high in MUFAs can improve glucose control and metabolic risk factors among patients with diabetes or stress-induced hyperglycaemia compared with a STDF.
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Disentangling the Effects of Monounsaturated Fatty Acids from Other Components of a Mediterranean Diet on Serum Metabolite Profiles: A Randomized Fully Controlled Dietary Intervention in Healthy Subjects at Risk of the Metabolic Syndrome.
Michielsen, CCJR, Hangelbroek, RWJ, Feskens, EJM, Afman, LA
Molecular nutrition & food research. 2019;(9):e1801095
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SCOPE The Mediterranean (MED) diet has been associated with a decreased risk of cardiovascular diseases. It is unclear whether this health effect can be mainly contributed to high intakes of monounsaturated fatty acids (MUFA), characteristic for the MED diet, or whether other components of a MED diet also play an important role. METHODS AND RESULTS A randomized fully controlled parallel trial is performed to examine the effects of the consumption of a saturated fatty acid rich diet, a MUFA-rich diet, or a MED diet for 8 weeks on metabolite profiles, in 47 subjects at risk of the metabolic syndrome. A total of 162 serum metabolites are assessed before and after the intervention by using a targeted NMR platform. Fifty-two metabolites are changed during the intervention (false discovery rate [FDR] p < 0.05). Both the MUFA and MED diet decrease exactly the same fractions of LDL, including particle number, lipid, phospholipid, and free cholesterol fraction (FDR p < 0.05). The MED diet additionally decreases the larger subclasses of very-low-density lipoprotein (VLDL), related VLDL fractions, VLDL-triglycerides, and serum-triglycerides (FDR p < 0.05). CONCLUSION The findings clearly demonstrate that the MUFA component is responsible for reducing LDL subclasses and fractions, and therefore causes an antiatherogenic lipid profile. Interestingly, consumption of the other components in the MED diet show additional health effects.
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Postprandial Lipemic Responses to Various Sources of Saturated and Monounsaturated Fat in Adults.
Sciarrillo, CM, Koemel, NA, Tomko, PM, Bode, KB, Emerson, SR
Nutrients. 2019;(5)
Abstract
BACKGROUND Postprandial lipemia (PPL) is a cardiovascular disease risk factor. However, the effects of different fat sources on PPL remain unclear. We aimed to determine the postprandial response in triglycerides (TG) to four dietary fat sources in adults. METHODS Participants completed four randomized meal trials. For each meal trial, participants (n = 10; 5M/5F) consumed a high-fat meal (HFM) (13 kcal/kg; 61% of total kcal from fat) with the fat source derived from butter, coconut oil, olive oil, or canola oil. Blood was drawn hourly for 6 h post-meal to quantify PPL. RESULTS Two-way ANOVA of TG revealed a time effect (p < 0.0001), but no time-meal interaction (p = 0.56), or meal effect (p = 0.35). Meal trials did not differ with regard to TG total (p = 0.33) or incremental (p = 0.14) area-under-the-curve. When stratified by sex and the TG response was averaged across meals, two-way ANOVA revealed a time effect (p < 0.0001), time-group interaction (p = 0.0001), and group effect (p = 0.048), with men exhibiting a greater response than women, although this difference could be attributed to the pronounced difference in BMI between men and women within the sample. CONCLUSION In our sample of young adults, postprandial TG responses to a single HFM comprised of different fat sources did not differ.
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Effect of high-carbohydrate or high-monounsaturated fatty acid diets on blood pressure: a systematic review and meta-analysis of randomized controlled trials.
Jovanovski, E, de Castro Ruiz Marques, A, Li, D, Ho, HVT, Blanco Mejia, S, Sievenpiper, JL, Zurbau, A, Komishon, A, Duvnjak, L, Bazotte, RB, et al
Nutrition reviews. 2019;(1):19-31
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CONTEXT Current dietary guidelines for cardiovascular disease risk management recommend restricting intake of saturated fatty acids (SFAs). However, the optimal macronutrient profile, in the context of a low-SFA diet, remains controversial. The blood-pressure effect of replacing SFAs in diets with monounsaturated fatty acids (MUFAs) compared with carbohydrate has not been quantified to date. OBJECTIVE To synthesize the evidence for the effect of substituting a high-carbohydrate (high-CHO) diet for a high-monounsaturated fatty acid (high-MUFA) diet on blood pressure, a systematic review and meta-analysis of randomized clinical trials in a population without health restrictions was conducted. DATA SOURCES MEDLINE, EMBASE, and Cochrane Central Register of Controlled Clinical Trials were searched through June 7, 2017. Randomized controlled trials of > 3 weeks duration that assessed the effect of high-MUFA diets in isocaloric substitution for high-CHO diets on systolic blood pressure (SBP) and diastolic blood pressure (DBP) were included. DATA EXTRACTION Data were pooled using the generic-inverse variance method with random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by Cochran Q statistic and quantified by the I2 statistic. The quality of the evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS Fourteen trials (n = 980 participants) were included in the analysis. Comparatively, the high-MUFA diets in isocaloric substitution for high-CHO diets did not demonstrate a greater reduction in blood pressure (SBP: MD, -0.08 mmHg [95%CI, -1.01 to 0.84], P = 0.86; DBP: MD = 0.01 mmHg [95%CI, -0.73 to 0.75], P = 0.98). The overall quality of the evidence was assessed as moderate. CONCLUSIONS In the context of low SFAs, high-MUFA diets in isocaloric substitution for high-CHO diets did not affect blood pressure in individuals with and without hypertension. Large-scale trials achieving higher MUFA targets are required to support these findings. CLINICALTRIALS.GOV ID NCT02626325.
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Evaluation of plasma and erythrocyte fatty acids C15:0, t-C16:1n-7 and C17:0 as biomarkers of dairy fat consumption in adolescents.
Slim, M, Ha, C, Vanstone, CA, Morin, SN, Rahme, E, Weiler, HA
Prostaglandins, leukotrienes, and essential fatty acids. 2019;:24-29
Abstract
INTRODUCTION Pentadecanoic (C15:0), heptadecanoic (C17:0) and trans-palmitoleic (t-C16:1n-7) fatty acids (FAs) are often used as biomarkers for dairy fat in adults. This study aimed to investigate the relationship between dairy product intake and these FAs in adolescents. MATERIAL AND METHODS Healthy adolescents were randomized to one of three groups (Group 1: control; Group 2: consume 3 dairy servings/day; and Group 3: consume ≥ 4 servings/d). C15:0, C17:0 and t-C16:1n-7 were quantified using gas chromatography. Dietary intakes were assessed by 24 h diet recalls. RESULTS No difference was observed in FAs at baseline or 6 months (mo), however, at 12 mo, erythrocyte C15:0 increased in group 3 (+0.37 µg/ml, p = 0.01). Dairy intake increased in both intervention groups (Group 2: +1.4 servings/d; Group 3: +2.4 servings/d, p < 0.0001) and positively correlated with erythrocyte C15:0 at 12 mo. CONCLUSION Erythrocyte FAs appear to be associated with increasing dairy intakes during adolescence.