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Increased serum cholesterol and long-chain fatty acid levels are associated with the efficacy of nivolumab in patients with non-small cell lung cancer.
Karayama, M, Inui, N, Inoue, Y, Yoshimura, K, Mori, K, Hozumi, H, Suzuki, Y, Furuhashi, K, Fujisawa, T, Enomoto, N, et al
Cancer immunology, immunotherapy : CII. 2022;(1):203-217
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Abstract
BACKGROUND Lipids have immunomodulatory functions and the potential to affect cancer immunity. METHODS The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab. RESULTS When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid. CONCLUSIONS Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.
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Association of the gut microbiota and fecal short-chain fatty acids with skeletal muscle mass and strength in children.
Chen, F, Li, Q, Chen, Y, Wei, Y, Liang, J, Song, Y, Shi, L, Wang, J, Mao, L, Zhang, B, et al
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2022;(1):e22109
Abstract
We aimed to investigate whether the gut microbiota and fecal short-chain fatty acids (SCFAs) are associated with skeletal muscle mass and strength in healthy Chinese children aged 6-9 years. In this study, 412 children were enrolled. 16S rRNA gene sequencing was used to characterize the gut microbiota compositions. Fecal SCFAs were quantified using high-performance liquid chromatography. Dual X-ray absorptiometry was used to measure the total body lean soft tissue mass (TSM), total body fat mass (TBF), appendicular skeletal muscle mass (ASM), and appendicular fat mass (AFM). TSM/height2 (TSMI), ASM/height2 (ASMI), TSM/weight (TSMR), ASM/weight (ASMR), and the ratio of TSM/TBF and ASM/AFM were calculated. Handgrip strength (HGS) was measured using the Jamar® Plus+ Hand Dynamometer. A multiple regression analysis after adjustment for covariates and multiple test correction showed some operational taxonomic units in partial least squares models identified by Multivariate methods with Unbiased Variable selection analysis such as genera of Faecalibacterium, Lachnospira, Lachnospiraceae_ND3007_group, and Lachnospiraceae_UCG-004 were positively correlated with at least one measure of TSM, TSMI, ASM, ASMI, and ASMI Z-score (β: 0.103-0.143, pFDR : .008-.032) but negatively correlated with at least one measure of TSMR, TSM/TBF, ASMR, ASM/AFM, and ASMR Z-score (β: -0.185 to 0.124, pFDR = .008-.045). Children with higher fecal butyric acid, acetic acid, and total SCFA levels exhibited higher TSM, ASM, TSMI, ASMI, and ASMI Z-score and lower TSM/TBF, ASM/AFM, TSMR, ASMR, and ASMR Z-score. However, after additional adjustment for TBF or body mass index, only the associations for Faecalitalea and Pyramidobacter still existed. Mediation analysis suggested that total body fat significantly mediated 66.3%-95.3% of the estimated association of microbiota and SCFAs with TSM, ASM, and ASMI Z-score. Our results suggest that the associations of gut microbiota and SCFAs with skeletal muscle quality in children may largely depend upon on total body fat content.
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Single nucleotide polymorphism of fatty acid desaturase gene and breast cancer risk in estrogen receptor subtype.
Preethika, A, Sonkusare, S, Suchetha Kumari, N
Gene. 2022;:146330
Abstract
BACKGROUND Breast cancer (BC) is the most common cancer of women and the second most common cancer overall globally. Data suggest that the plasma concentration of omega fatty acids (n-3 and n-6) and the impact of the genetic variant are associated with diet-related inflammatory disease, BC. This study was aimed to find an association between genetic variant rs174537 of fatty acid desaturase gene 1(FADS 1) and breast cancer estrogen receptor subtype. METHODOLOGY Hundred and two blood samples from women were quantified for fatty acids by gas chromatography. SNP rs 174537(G > T) showed maximum variability and the strongest genetic determinant in the Genome-wide association study were genotyped using Sanger sequencing. RESULTS The highest tertile of ALA showed a significantly reduced risk of BC compared to the lowest tertile (OR = 0.2, 95 %CL = 0.1-1.14, P = 0.03). Median values of ALA were higher in GT/TT genotype in ER +ve molecular subtype (P = 0.03) and DPA was higher in GG genotype of ER-ve molecular subtype (P = 0.037). When both the groups were put together the highest tertile of GG tertile showed significantly reduced risk of BC compared with the other lowest tertiles of GG and GT/TT genotypes (OR, 95% CL = 0.45(0.2-0.9). CONCLUSION The high levels of arachidonic acid and low levels of n-3 fatty acids result in a pro-inflammatory milieu and that these pro-inflammatory effects might contribute to BC. We conclude that the individuals with genetically determined lower activity of FADS1(minor allele T) will derive greater advantage from n-3 FAs than those with higher FADS1 activity (G allele) and reduce the BC risk.
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Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis.
Trieu, K, Bhat, S, Dai, Z, Leander, K, Gigante, B, Qian, F, Korat, AVA, Sun, Q, Pan, XF, Laguzzi, F, et al
PLoS medicine. 2021;(9):e1003763
Abstract
BACKGROUND We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality. METHODS AND FINDINGS We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose-response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case-cohort, or nested case-control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. CONCLUSIONS In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.
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Bempedoic Acid: A New Tool in the Battle Against Hyperlipidemia.
Powell, J, Piszczatoski, C
Clinical therapeutics. 2021;(2):410-420
Abstract
PURPOSE This article discusses the pharmacology of bempedoic acid, the trials that led to United States Food and Drug Administration (FDA) approval of its use, and the overall safety and efficacy of this therapy in heterozygous familial hypercholesterolemia, established atherosclerotic cardiovascular disease (ASCVD), and hyperlipidemia. METHODS A database search of PubMed and ClinicalTrials.gov was conducted for articles published between January 2012 to September 2020 and containing the key words bempedoic acid, ezetimibe, Nexletol and Nexlizet. Trials from the CLEAR series were selected, as they played a pivotal role in the establishment of FDA approval, along with additional trials published after FDA approval, which provided novel evidence on the use of bempedoic acid in the treatment of hypercholesterolemia. Publications that were not randomized, controlled trials were not included in this review. Only randomized controlled trials in which ezetimibe was used in conjunction with bempedoic acid were included in this review as they were relevant to the new FDA approval of bempedoic acid. FINDINGS The findings of the present review show that bempedoic acid is both an effective and well-tolerated option for the treatment of hypercholesterolemia when used without ezetimibe in addition to standard therapy. It also appears that the combination with ezetimibe increases the cholesterol-lowering effect more than either agent alone when added to standard therapy. IMPLICATIONS Hypercholesteremia continues to be a major contributing factor leading to ASCVD. Bempedoic acid is an additional treatment option, along with both statins and diet and exercise, for reducing cholesterol levels and ASCVD events. With the new FDA approval, bempedoic acid may offer an effective therapy for reducing low-density lipoprotein cholesterol in patients at high risk for cardiovascular events due to established ASCVD or heterozygous familial hypercholesterolemia.
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HPLC with spectrophotometric or mass spectrometric detection for quantifying very-long chain fatty acids in human plasma and its association with cardiac risk factors.
Shrestha, R, Chen, Z, Gao, Z, Chen, Y, Okada, E, Ukawa, S, Nakagawa, T, Nakamura, K, Tamakoshi, A, Chiba, H, et al
Annals of clinical biochemistry. 2021;(5):400-410
Abstract
BACKGROUND We developed and compared two liquid chromatography methods, one with UV/Visible spectrophotometric detection (HPLC) and the other with mass spectrometric detection (LC-MS), for quantifying very-long chain fatty acids (VLCFA) in human plasma. Association of VLCFA with various cardiovascular risk factors were evaluated. METHOD Fasting blood samples were collected from 541 human volunteers (242 men and 299 women; mean age ±SD, 58.9 ± 12.4 years), including 429 and 112 individuals with and without hypertriglyceridemia, respectively. Esterified VLCFA were saponified and derivatized with 2-nitrophenylhydrazine. Separation of VLCFA species was achieved with C4 Mightysil column (HPLC) and Ascentis Express Phenyl-Hexyl column (LC-MS) followed by spectrophotometric and selected-reaction monitoring mode of mass spectrometric detection, respectively. RESULTS The HPLC assay of VLCFA was precise with intra-assay imprecision of 2.5% to 6.9% and inter-assay imprecision of 3.2% to 9.5%. Moreover, there was an excellent correlation (r > 0.96) between HPLC and LC-MS methods. The 95 percentile reference intervals (RI; upper limit) of VLCFA were determined to be 41.3 µmol/L in healthy volunteers. Plasma VLCFA were significantly correlated with triglycerides (Spearman's ρ = 0.306, P < 0.001) and total cholesterol (Spearman's ρ = 0.251, P < 0.001). All species of VLCFA were significantly elevated in hypertriglyceridaemic individuals compared with control. CONCLUSION We established LC-based assays of VLCFA with either spectrophotometry or mass spectrometry as a detection system. Hypertriglyceridaemia is significantly associated with elevated concentration of each species of VLCFA.
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Dietary fatty acids as nutritional modulators of sirtuins: a systematic review.
Caldas, APS, Rocha, DMUP, Bressan, J, Hermsdorff, HHM
Nutrition reviews. 2021;(2):235-246
Abstract
CONTEXT The sirtuins (SIRT1 to SIRT7) constitute a family of highly conserved nicotinamide adenine dinucleotide-dependent proteins. When activated, sirtuins control essential cellular processes to maintain metabolic homeostasis, while lack of expression of sirtuins has been related to chronic disease. OBJECTIVE The aim of this systematic review is to analyze the role of fat consumption as a modulator of human sirtuins. DATA SOURCES This review was conducted according to PRISMA guidelines. Studies were identified by searches of the electronic databases PubMed/MEDLINE, Scopus, and Web of Science. STUDY SELECTION Randomized clinical trials assessing the effect of fatty acid consumption on sirtuin mRNA expression, sirtuin protein expression, or sirtuin protein activity were eligible for inclusion. DATA EXTRACTION Two authors screened and determined the quality of the studies; disagreements were resolved by the third author. All authors compared the compiled data. RESULTS Seven clinical studies with 3 different types of interventions involving healthy and nonhealthy participants were selected. Only SIRT1 and SIRT3 were evaluated. Overall, the evidence from clinical studies to date is insufficient to understand how lipid consumption modulates sirtuins in humans. The best-characterized mechanism highlights oleic acid as a natural activator of SIRT1. CONCLUSION These results draw attention to a new field of interest in nutrition science. The possible activation of sirtuins by dietary fat manipulation may represent an important nutritional strategy for management of chronic and metabolic disease. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42018114456.
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Rapid measurement of fatty acid content during flour storage using a color-sensitive gas sensor array: Comparing the effects of swarm intelligence optimization algorithms on sensor features.
Jiang, H, Liu, T, He, P, Ding, Y, Chen, Q
Food chemistry. 2021;:127828
Abstract
The fatty acid content of flour is an important indicator for determining the deterioration of flour. We propose a novel rapid measurement method for fatty acid content during flour storage based on a self-designed color-sensitive gas sensor array. First, a color-sensitive gas sensor array was prepared to capture the odor changes during flour storage. The sensor features were then optimized using genetic algorithm (GA), ant colony optimization (ACO) and particle swarm optimization (PSO). Finally, back propagation neural network (BPNN) models were established to measure the fatty acid content during flour storage. Experimental results showed that the optimization effects of the three algorithms improved in the following order: GA < ACO < PSO, for the sensor features optimization. In the validation set, the determination coefficient of the best PSO-BPNN model was 0.9837. The overall results demonstrate that the models established on the optimized features can realize rapid measurements of fatty acid content during flour storage.
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Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial.
Geidl-Flueck, B, Hochuli, M, Németh, Á, Eberl, A, Derron, N, Köfeler, HC, Tappy, L, Berneis, K, Spinas, GA, Gerber, PA
Journal of hepatology. 2021;(1):46-54
Abstract
BACKGROUND & AIMS Excessive fructose intake is associated with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. We aimed to determine whether fructose elicits specific effects on lipid metabolism independently of excessive caloric intake. METHODS A total of 94 healthy men were studied in this double-blind, randomized trial. They were assigned to daily consumption of sugar-sweetened beverages (SSBs) containing moderate amounts of fructose, sucrose (fructose-glucose disaccharide) or glucose (80 g/day) in addition to their usual diet or SSB abstinence (control group) for 7 weeks. De novo fatty acid (FA) and triglyceride synthesis, lipolysis and plasma free FA (FFA) oxidation were assessed by tracer methodology. RESULTS Daily intake of beverages sweetened with free fructose and fructose combined with glucose (sucrose) led to a 2-fold increase in basal hepatic fractional secretion rates (FSR) compared to control (median FSR %/day: sucrose 20.8 (p = 0.0015); fructose 19.7 (p = 0.013); control 9.1). Conversely, the same amounts of glucose did not change FSR (median of FSR %/day 11.0 (n.s.)). Fructose intake did not change basal secretion of newly synthesized VLDL-triglyceride, nor did it alter rates of peripheral lipolysis, nor total FA and plasma FFA oxidation. Total energy intake was similar across groups. CONCLUSIONS Regular consumption of both fructose- and sucrose-sweetened beverages in moderate doses - associated with stable caloric intake - increases hepatic FA synthesis even in a basal state; this effect is not observed after glucose consumption. These findings provide evidence of an adaptative response to regular fructose exposure in the liver. LAY SUMMARY This study investigated the metabolic effects of daily sugar-sweetened beverage consumption for several weeks in healthy lean men. It revealed that beverages sweetened with the sugars fructose and sucrose (glucose and fructose combined), but not glucose, increase the ability of the liver to produce lipids. This change may pave the way for further unfavorable effects on metabolic health. CLINICAL TRIAL REGISTRATION NUMBER NCT01733563.
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Ampicillin used in aseptic processing influences the production of pigments and fatty acids in Chlorella sorokiniana.
Wang, W, Sheng, Y
World journal of microbiology & biotechnology. 2021;(1):3
Abstract
Ampicillin sodium salt (AMP) is commonly and effectively used to prevent bacterial infection in algal culture, but the response of algal strains to AMP has not been investigated. In this study, Chlorella sorokiniana was selected to evaluate the influence of AMP on algae. AMP enhanced the contents of chlorophyll and two fatty acids, myristic acid (C22:1N9) and tetracosanoic acid (C6:0), but inhibited the growth, carotenoid production, and contents of 16 fatty acids in C. sorokiniana. A global transcriptome analysis from experimental data identified 3 825 upregulated and 1 432 downregulated differentially expressed genes (DEGs) in C. sorokiniana. The upregulated DEGs, such as hemB/alaD, mmaB/pduO, cox15/ctaA, fxN, cpoX/hemF, and earS/gltX, were enriched in the porphyrin and chlorophyll metabolism pathways, whereas the downregulated DEGs, including lcyB (crtL1), crtY (lcyE, crtL2), lut1 (CYP97C1), z-isO, crtZ and crtisO (crtH), were enriched in the carotenoid biosynthesis pathway, and the downregulated DEGs, abH, fadD, fabF, acsL, fabG, and accD were enriched in the fatty acid biosynthesis pathway. Thus, the use of AMP to obtain an axenic strain revealed that AMP might affect the regulatory dynamics and the results of the metabolic process in C. sorokiniana. The data obtained in the study provide foundational information for algal purification and aseptic processing.