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Raspberry consumption: identification of distinct immune-metabolic response profiles by whole blood transcriptome profiling.
Franck, M, de Toro-Martín, J, Varin, TV, Garneau, V, Pilon, G, Roy, D, Couture, P, Couillard, C, Marette, A, Vohl, MC
The Journal of nutritional biochemistry. 2022;:108946
Abstract
Numerous studies have reported that diets rich in phenolic compounds are beneficial to immune-metabolic health, yet these effects are heterogeneous and the underlying mechanisms are poorly understood. To investigate the inter-individual variability of the immune-metabolic response to raspberry consumption, whole-blood RNAseq data from 24 participants receiving 280 g/d of raspberries for 8 weeks were used for the identification of responsiveness subgroups by using partial least squares-discriminant analysis (PLSDA) and hierarchical clustering. Transcriptomic-based clustering regrouped participants into two distinct subgroups of 13 and 11 participants, so-called responders and non-responders, respectively. Following raspberry consumption, a significant decrease in triglycerides, cholesterol and C-reactive protein levels were found in responders, as compared to non-responders. Two major gene expression components of 100 and 220 genes were identified by sparse PLSDA as those better discriminating responders from non-responders, and functional analysis identified pathways related to cytokine production, leukocyte activation and immune response as significantly enriched with most discriminant genes. As compared to non-responders, the plasma lipidomic profile of responders was characterized by a significant decrease in triglycerides and an increase in phosphatidylcholines following raspberry consumption. Prior to the intervention, a distinct metagenomic profile was identified by PLSDA between responsiveness subgroups, and the Firmicutes-to-Bacteroidota ratio was found significantly lower in responders, as compared to non-responders. Findings point to this transcriptomic-based clustering approach as a suitable tool to identify distinct responsiveness subgroups to raspberry consumption. This approach represents a promising framework to tackle the issue of inter-individual variability in the understanding of the impact of foods on immune-metabolic health.
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Dose-dependent reductions in plasma ceramides after anthocyanin supplementation are associated with improvements in plasma lipids and cholesterol efflux capacity in dyslipidemia: A randomized controlled trial.
Zhao, Y, Xu, H, Tian, Z, Wang, X, Xu, L, Li, K, Gao, X, Fan, D, Ma, X, Ling, W, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1871-1878
Abstract
BACKGROUND & AIMS Plasma ceramides have been identified as novel risk factors for metabolic and cardiovascular diseases. We aimed to evaluate the effects of dietary anthocyanins on plasma ceramides and to disentangle whether the alterations in ceramides could be related with those in other cardiometabolic risk factors in the dyslipidemia. METHODS In a randomized double-blinded placebo-controlled trial, 176 eligible dyslipidemia subjects were randomly assigned into four groups receiving placebo, 40, 80, or 320 mg/day anthocyanins, respectively for 12 weeks. RESULTS A total of 169 subjects completed the study. After 12-week intervention, dietary anthocyanins dose-dependently reduced plasma concentrations of all six ceramide species in the dyslipidemia subjects (all Ptrend values < 0.05). Specifically, 320 mg/day anthocyanins effectively lowered plasma N-palmitoylsphingosine (Cer 16:0, mean change: -28.3 ± 41.2 versus 2.9 ± 38.2, nmol/L, P = 0.018) and N-tetracosanoylsphingosine (Cer 24:0, mean change: -157.1 ± 493.9 versus 10.7 ± 439.9, nmol/L, P = 0.002) compared with the placebo. The declines in plasma Cer 16:0 and Cer 24:0 were significantly correlated with the decreases in plasma non-high-density lipoprotein cholesterol (nonHDL-C, Spearman's r = 0.32, P = 0.040 for Cer 16:0; Spearman's r = 0.35, P = 0.026 for Cer 24:0), apolipoprotein B (Spearman's r = 0.33, P = 0.031 for Cer 16:0; Spearman's r = 0.48, P = 0.002 for Cer 24:0), and total cholesterol (Spearman's r = 0.34, P = 0.026 for Cer 16:0; Spearman's r = 0.31, P = 0.042 for Cer 24:0) after 12-week 320 mg/day anthocyanin administration. Besides, we found that anthocyanins at 320 mg/day also markedly enhanced cholesterol efflux capacity in the dyslipidemia, the changes of which were positively associated with the reductions in Cer 16:0 (Spearman's r = 0.42, P = 0.006) independent of HDL-C and apolipoprotein A-I. CONCLUSIONS Reductions in plasma Cer 16:0 and Cer 18:0 after 12-week anthocyanin intervention were dose-dependently associated with improvements in plasma lipids and cholesterol efflux capacity in the dyslipidemia. CLINICAL TRIAL REGISTRATION The study was registered at ClinicalTrials.gov with the identifier No. NCT03415503.
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Hypocaloric diet with lower meal frequency did not affect weight loss, body composition and insulin responsiveness, but improved lipid profile: a randomized clinical trial.
Grangeiro, ÉD, Trigueiro, MS, Siais, LO, Paiva, HM, Sola-Penna, M, Alves, MR, Rosado, EL
Food & function. 2021;(24):12594-12605
Abstract
Dietary approaches are essential to control obesity, but the effectiveness of changes in meal frequency (MF) as a strategy for body weight loss or maintenance remain unclear. This study aimed to evaluate the influence of MF of a hypocaloric diet on weight loss, body composition, active ghrelin levels and metabolic indicators of obese women. This is a randomized, parallel clinical trial, including 40 women divided into two groups that received a hypocaloric diet with different MFs: MF6: six meals per day, and MF3: three meals per day. Dietary, laboratory, anthropometric and body composition indicators were assessed, as well as energy expenditure (EE), before and after the 90 days of the intervention. Dietary consumption did not differ between groups, before or after intervention. The two groups reduced their energy intake after intervention, but there were no differences between the groups. Waist circumference (WC) was reduced and resting metabolic rate had increased in the MF3 group at the end compared to baseline. Moreover, there was a significant difference in the triglyceride levels between groups after intervention, with an important reduction in the MF3 group, although changes in body composition, blood glucose, plasma ghrelin levels and EE variables did not differ between the groups at the end. It is concluded that, the hypocaloric diet with different MF each day did not change weight loss, body composition or insulin responsiveness, but there was an improvement of triglyceridemia in the MF3 group. The present study suggests that eating snacks between meals is not an important factor for weight loss and improvement of metabolic health in women with obesity.
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A combination of single nucleotide polymorphisms is associated with the interindividual variability in the blood lipid response to dietary fatty acid consumption in a randomized clinical trial.
Rajendiran, E, Lamarche, B, She, Y, Ramprasath, V, Eck, P, Brassard, D, Gigleux, I, Levy, E, Tremblay, A, Couture, P, et al
The American journal of clinical nutrition. 2021;(2):564-577
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Abstract
BACKGROUND Blood lipid concentrations display high interindividual variability in response to dietary interventions, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explain a limited fraction of the variability of these complex phenotypes. OBJECTIVE We aimed to identify combinations of SNPs associated with the variability in LDL cholesterol and triglyceride (TG) concentration changes following 5 dietary interventions. DESIGN In a multicenter randomized crossover trial, 92 participants with elevated waist circumference and low HDL cholesterol concentrations consumed 5 isoenergetic diets for 4 wk: a diet rich in saturated fatty acids (SFAs) from cheese, SFA from butter, monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs), and a diet higher in carbohydrates (CHO). The association between 22 candidate SNPs in genes involved in lipid and bile acid metabolism and transport and changes in LDL cholesterol and TG concentrations was assessed with univariate statistics followed by partial least squares regression. RESULTS Endpoint LDL cholesterol concentrations were significantly different (cheese: 3.18 ± 0.04, butter: 3.31 ± 0.04, MUFA 3.00 ± 0.04, PUFA 2.81 ± 0.04, CHO: 3.11 ± 0.04 mmol/L; P < 0.001) while endpoint TG concentrations were not (P = 0.117). Both displayed consistently elevated interindividual variability following the dietary interventions (CVs of 34.5 ± 2.2% and 55.8 ± 1.8%, respectively). Among the 22 candidate SNPs, only ABCA1-rs2066714 and apolipoprotein E (APOE) isoforms exhibited consistent significant effects, namely on LDL cholesterol concentrations. However, several SNPs were significantly associated with changes in LDL cholesterol and TG concentrations in a diet-specific fashion. Generated multivariate models explained from 16.0 to 33.6% of the interindividual variability in LDL cholesterol concentration changes and from 17.5 to 32.0% of that in TG concentration changes. CONCLUSIONS We report combinations of SNPs associated with a significant part of the variability in LDL cholesterol and TG concentrations following dietary interventions differing in their fatty acid profiles.
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The Prebiotic Effects of Oats on Blood Lipids, Gut Microbiota, and Short-Chain Fatty Acids in Mildly Hypercholesterolemic Subjects Compared With Rice: A Randomized, Controlled Trial.
Xu, D, Feng, M, Chu, Y, Wang, S, Shete, V, Tuohy, KM, Liu, F, Zhou, X, Kamil, A, Pan, D, et al
Frontiers in immunology. 2021;:787797
Abstract
Phytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However, deeper insights into its mechanism remain unclear. In this randomized controlled study, we assigned 210 mildly hypercholesterolemic subjects from three study centers across China (Beijing, Nanjing, and Shanghai) to consume 80 g of oats or rice daily for 45 days. Plasma lipid profiles, short chain fatty acids (SCFAs), and fecal microbiota were measured. The results showed that total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) decreased significantly with both oats and rice intake after 30 and 45 days. The reduction in TC and non-HDL-C was greater in the participants consuming oats compared with rice at day 45 (p = 0.011 and 0.049, respectively). Oat consumption significantly increased the abundance of Akkermansia muciniphila and Roseburia, and the relative abundance of Dialister, Butyrivibrio, and Paraprevotella, and decreased unclassified f-Sutterellaceae. In the oat group, Bifidobacterium abundance was negatively correlated with LDL-C (p = 0.01, r = -0.31) and, TC and LDL-C were negatively correlated to Faecalibacterium prausnitzii (p = 0.02, r = -0.29; p = 0.03, r = -0.27, respectively). Enterobacteriaceae, Roseburia, and Faecalibacterium prausnitzii were positively correlated with plasma butyric acid and valeric acid concentrations and negatively correlated to isobutyric acid. HDL-C was negatively correlated with valeric acid (p = 0.02, r = -0.25) and total triglyceride (TG) was positively correlated to isovaleric acid (p = 0.03, r = 0.23). Taken together, oats consumption significantly reduced TC and LDL-C, and also mediated a prebiotic effect on gut microbiome. Akkermansia muciniphila, Roseburia, Bifidobacterium, and Faecalibacterium prausnitzii, and plasma SCFA correlated with oat-induced changes in plasma lipids, suggesting prebiotic activity of oats to modulate gut microbiome could contribute towards its cholesterol-lowering effect.
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11βHSD1 Inhibition with AZD4017 Improves Lipid Profiles and Lean Muscle Mass in Idiopathic Intracranial Hypertension.
Hardy, RS, Botfield, H, Markey, K, Mitchell, JL, Alimajstorovic, Z, Westgate, CSJ, Sagmeister, M, Fairclough, RJ, Ottridge, RS, Yiangou, A, et al
The Journal of clinical endocrinology and metabolism. 2021;(1):174-187
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BACKGROUND The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH). METHODS We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry. RESULTS Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased high-density lipoprotein [HDL] and cholesterol/HDL ratio), markers of hepatic function (decreased alkaline phosphatase and gamma-glutamyl transferase), and increased lean muscle mass (1.8%, P < .001). No changes in body mass index, fat mass, and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass. CONCLUSIONS These beneficial metabolic changes represent a reduction in risk factors associated with raised intracranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia.
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Pharmacometabolomic profiles in type 2 diabetic subjects treated with liraglutide or glimepiride.
Jendle, J, Hyötyläinen, T, Orešič, M, Nyström, T
Cardiovascular diabetology. 2021;(1):237
Abstract
BACKGROUND Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) leads to multiple metabolic changes, reduction in glucose levels and body weight are well established. In people with type 2 diabetes, GLP-1 RAs reduce the risk of cardiovascular (CV) disease and may also potentially represent a treatment for fatty liver disease. The mechanisms behind these effects are still not fully elucidated. The aim of the study was to investigate whether treatment with liraglutide is associated with favourable metabolic changes in cases of both CV disease and fatty liver disease. METHODS In a prespecified post-hoc analysis of a double-blind, placebo-controlled trial in 62 individuals with type 2 diabetes (GLP-1 RA liraglutide or glimepiride, both in combination with metformin), we evaluated the changes in plasma molecular lipids and polar metabolites after 18 weeks of treatment. The lipids and polar metabolites were measured by using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS). RESULTS In total, 340 lipids and other metabolites were identified, covering 14 lipid classes, bile acids, free fatty acids, amino acids and other polar metabolites. We observed more significant changes in the metabolome following liraglutide treatment compared to with glimepiride, particularly as regards decreased levels of cholesterol esters hexocyl-ceramides, lysophosphatidylcholines, sphingolipids and phosphatidylcholines with alkyl ether structure. In the liraglutide-treated group, lipids were reduced by approximately 15% from baseline, compared to a 10% decrease in the glimepiride group. At the pathway level, the liraglutide treatment was associated with lipid, bile acid as well as glucose metabolism, while glimepiride treatment was associated with tryptophan metabolism, carbohydrate metabolism, and glycerophospholipid metabolism. CONCLUSIONS Compared with glimepiride, liraglutide treatment led to greater changes in the circulating metabolome, particularly regarding lipid metabolism involving sphingolipids, including ceramides. Our findings are hypothesis-generating and shed light on the underlying biological mechanisms of the CV benefits observed with GLP-1 RAs in outcome studies. Further studies investigating the role of GLP-1 RAs on ceramides and CV disease including fatty liver disease are warranted. TRIAL REGISTRATION NCT01425580.
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Effects of Danhong injection on cardiac function and blood lipid in patients with angina pectoris of coronary heart disease: A protocol for randomized, double-blind, placebo-controlled clinical trial.
Liang, J, He, X, Zhou, H, Liang, P
Medicine. 2021;(43):e27479
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BACKGROUND Angina pectoris of coronary heart disease is the leading cause of death worldwide. Danhong injection is a supplement for angina pectoris of coronary heart disease. A large number of studies have confirmed its efficacy and safety. However, there is no rigorous clinical study to evaluate the effects of Danhong injection on cardiac function and blood lipid in patients with angina pectoris of coronary heart disease. METHODS This is a prospective, randomized, double-blind, placebo-controlled trial to study the effects of Danhong injection on cardiac function and lipid profile in patients with angina pectoris of coronary heart disease. Participants will be randomly divided into treatment group and control group. The treatment group will be treated with Danhong injection and the control group will be treated with placebo under basic treatment according to recommended guideline, and followed up for 3 months after 14 consecutive days of treatment. Outcomes include: cardiac function (left ventricular end-diastolic diameter); left ventricular end-systolic diameter; left ventricular ejection fraction, blood lipid levels (total cholesterol; triacylglycerol; low density lipoprotein cholesterol; high density lipoprotein cholesterol), the number of angina attacks per week, total amount of nitroglycerin tablets, and adverse reactions. DISCUSSION This study will evaluate the efficacy of Danhong injection in improving cardiac function and blood lipid in patients with angina pectoris of coronary heart disease. The results of this study will provide reference for clinical use of Danhong injection to improve cardiac function and blood lipid in patients with angina pectoris of coronary heart disease.Trial registration: OSF Registration number: DOI 10.17605/OSF.IO/TPZJ5.
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The effects of KaiXinSan on depression and its association with lipid profiles: A randomized, double-blinded, placebo-controlled trial.
Hu, Y, Chen, C, Wang, Y, Yang, W, Wang, Y, Zhu, W, Yan, C, Liu, P
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2021;:153467
Abstract
BACKGROUND Traditional Chinese medicine (TCM) KaiXinSan (KXS) has been used to treat depressed patients for a long time, but its potential underlying mechanisms have not been fully understood. HYPOTHESIS KXS could mitigate symptoms of patients with atypical depression at least partly via regulating lipid equilibrium. METHODS Patients meeting DSM-IV criteria for mild or moderate depression were assigned into placebo (N = 68) or KXS 3.2 g/day (N = 66) groups in a randomized, double-blinded, placebo-controlled, parallel clinical trial to investigate the anti-depressive efficacy of KXS and its association with serum lipid profile. RESULTS The HAMD score and SDS score at 8 weeks were significantly improved in KXS-treated patients the N-BACK accuracy rate was also increased after 8 weeks of KXS treatment compared with baseline. These results indicated that KXS not only improved the specific symptoms of depression, but also had a beneficial effect on cognitive function related working memory. More importantly, KXS treatment improved patients' lipid profile by reducing the ratios of LDL/HDL and ApoB/ApoA1 (p < 0.05), as well as ApoC3 level. Moreover, subgroup analysis found that HAMD score was significantly higher in patients with high lipid profile than in those with normal lipid profile, and lipid improvement after 8 weeks of KXS treatment was more obvious in depressed patients with high lipid profile than with normal lipid profile. CONCLUSION KXS could mitigate symptoms of patients with minor and modest depression at least partly via regulating lipid equilibrium. Its might shed light that KXS may likely contributes to depressed patients with other cardio-metabolic diseases.
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The effects of canola and olive oils consumption compared to sunflower oil, on lipid profile and hepatic steatosis in women with polycystic ovarian syndrome: a randomized controlled trial.
Yahay, M, Heidari, Z, Allameh, Z, Amani, R
Lipids in health and disease. 2021;(1):7
Abstract
BACKGROUND Polycystic Ovarian Syndrome (PCOS) is one of the most common endocrinopathies and metabolic disorders in women during their reproductive years. It is often associated with dyslipidemia and other risk factors of cardiovascular diseases (CVD). This study was aimed to evaluate dietary intervention effects with canola and olive oils compared to sunflower oil on lipid profile and fatty liver severity among women with PCOS. METHOD This study was a 10-week intervention including 72 women with PCOS. Patients were randomly assigned to three groups for receiving 25 g/day canola, olive, or sunflower oils for 10 weeks. The primary and secondary outcomes were to assess changes in lipid profile and in fatty liver severity, respectively. RESULT At the end of the study, 72 patients with a mean age of 29.31 were analysed. Canola oil consumption resulted in a significant reduction in serum levels of TG (P = 0.002) and TC/HDL (P = 0.021), LDL/HDL (P = 0.047), and TG/HDL (P = 0.001) ratios, however, there was no significant reduction in lipid profile following olive oil consumption. Canola (P < 0.001) and olive oils (P = 0.005) could significantly reduce the fatty liver grade. Moreover, HOMA-IR in both canola (P < 0.001) and olive (P = 0.004) groups was significantly decreased. CONCLUSION In total, compared to olive and sunflower oils, significant improvements in lipid profile, liver function, and HOMA-IR were observed following canola oil consumption in women with PCOS. TRIAL REGISTRATION IR.MUI. RESEARCH REC.1397.315. Registered 30 JUNE 2019 - Retrospectively registered, https://www.irct.ir/trial/38684.