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Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis.
Scholz, M, Horn, K, Pott, J, Gross, A, Kleber, ME, Delgado, GE, Mishra, PP, Kirsten, H, Gieger, C, Müller-Nurasyid, M, et al
Nature communications. 2022;(1):143
Abstract
Phytosterol serum concentrations are under tight genetic control. The relationship between phytosterols and coronary artery disease (CAD) is controversially discussed. We perform a genome-wide meta-analysis of 32 phytosterol traits reflecting resorption, cholesterol synthesis and esterification in six studies with up to 9758 subjects and detect ten independent genome-wide significant SNPs at seven genomic loci. We confirm previously established associations at ABCG5/8 and ABO and demonstrate an extended locus heterogeneity at ABCG5/8 with different functional mechanisms. New loci comprise HMGCR, NPC1L1, PNLIPRP2, SCARB1 and APOE. Based on these results, we perform Mendelian Randomization analyses (MR) revealing a risk-increasing causal relationship of sitosterol serum concentrations and CAD, which is partly mediated by cholesterol. Here we report that phytosterols are polygenic traits. MR add evidence of both, direct and indirect causal effects of sitosterol on CAD.
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Identification of novel lipid metabolic biomarkers associated with poor adrenocortical carcinoma prognosis using integrated bioinformatics.
Subramanian, C, Cohen, MS
Surgery. 2022;(1):119-129
Abstract
BACKGROUND Adrenocortical carcinoma while rare, often presents with advanced metastatic disease carrying a 5-year survival of <15%. Despite adrenocortical carcinoma tumors having high avidity for cholesterol, the role of lipids in adrenocortical carcinoma has not been well described. Therefore, we performed an integrated bioinformatic analysis to identify novel lipid biomarkers correlating with poor survival that may help identify adrenocortical carcinoma tumor progression or therapy resistance. METHODS A meta-analysis of collated adrenocortical carcinoma studies from the correlation engine identified lipid metabolism genes differentially expressed between adrenocortical carcinoma and the normal adrenal, which were then selected for enrichment analysis by the Database for Annotation, Visualization and Integrated Discovery database. A protein-protein interaction network of genes was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Top hub genes identified were validated using the Xena database. Survival analysis of hub genes was performed in the R2 genomic analysis platform using The Cancer Genome Atlas program data set. RESULTS Examination of pathways by correlation engine identified a unique subset of lipid metabolism-related genes that are differentially regulated in adrenocortical carcinoma tumors versus normal tissues (P < .01). Enrichment pathway analysis in Database for Annotation, Visualization and Integrated Discovery indicated that genes involved in sphingolipid, steroid, and peroxisome proliferator-activated receptor-α metabolism is upregulated in adrenocortical carcinoma, whereas glycerol phospholipid, fatty acid, and phosphatidylinositol metabolism are downregulated. Survival analysis of differentially regulated genes indicated that upregulation of SGPL1, FDFT1, SQLE and downregulation of PIK3C2B, PIK3CD, SYNJ2, DGAT1, PLA2G16, PLD1, GPD1 are all significantly associated with poor overall survival (P < .05) in adrenocortical carcinoma patients. CONCLUSION Upregulation of sphingolipid and steroid synthesis genes and downregulation of phosphatidylinositol and glycerol phospholipid metabolism are associated with worse survival in patients with adrenocortical carcinoma.
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Raloxifene has favorable effects on the lipid profile in women explaining its beneficial effect on cardiovascular risk: A meta-analysis of randomized controlled trials.
Yang, F, Li, N, Gaman, MA, Wang, N
Pharmacological research. 2021;:105512
Abstract
There is robust evidence that the appropriate treatment of dyslipidaemia substantially reduces cardiovascular disease-related morbidity and mortality. Raloxifene is a selective oestrogen receptor modulator that also interferes with the lipid metabolism and may be of aid in the management of lipid abnormalities in females. Therefore, we conducted a systematic review and meta-analysis of the available randomized clinical trials (RCTs) exploring the effect of raloxifene on the lipid profile in women. The Scopus, Web of Science, PubMed/Medline and EMBASE databases were systematically and independently searched by two assessors from inception until 20 November 2020 without time and language restrictions. The overall findings were generated from 30 eligible RCTs. As compared to controls, raloxifene resulted in a significant elevation of the high-density lipoprotein-cholesterol (HDL-C) (WMD: 2.41 mg/dL, 95% CI: 0.84-3.97, P = 0.003) and a significant reduction of the total cholesterol (TC) (WMD:-14.84 mg/dL, 95% CI: -20.37 to -9.317, P = 0.000) and of the low-density lipoprotein-cholesterol (LDL-C) (WMD: -17 mg/dL, 95% CI: -25.77, -8.22, P = 0.000). In the stratified analysis, a significant decrease of serum triglycerides (TG) (WMD: -22.06 mg/dL) was achieved in the RCTs with a duration of ≤ 26 weeks (WMD -8.70 mg/dL) and with baseline TG concentrations of ≥ 130 mg/dL (WMD: -23.02 mg/dL). In conclusion, raloxifene treatment can increase HDL-C and lower LDL-C and TC. In terms of TG, a significant decrease can be observed if the administration of raloxifene lasts ≤ 26 weeks and if the baseline TG concentrations are ≥ 130 mg/dL.
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Effect of tai chi on glycaemic control, lipid metabolism and body composition in adults with type 2 diabetes: A meta-analysis and systematic review.
Guo, S, Xu, Y, Qin, J, Chen, Y, You, Y, Tao, J, Liu, Z, Huang, J
Journal of rehabilitation medicine. 2021;(3):jrm00165
Abstract
OBJECTIVE The aim of this systematic review was to evaluate the effects of tai chi on metabolic control and body composition indicators in patients with type 2 diabetes mellitus. DESIGN Systematic review and meta-analysis of existing literature. METHODS Electronic resource databases were searched to collect eligible studies. Two reviewers selected studies and independently evaluated method-ological quality. RESULTS Twenty-three studies were included in this meta-analysis. The pooled results showed that tai chi had significant effects in improving metabolic indices, such as fasting blood glucose (mean differ-ence (MD) = -1.04; 95% confidence interval (95% CI) -1.42 to 0.66; p < 0.01) and total cholesterol (MD = -0.50; 95% CI -0.86 to -0.13; p < 0.01) compared with conventional clinical therapy. Most in-dices did not support the use of tai chi over aerobic exercise, except for glycated haemoglobin (HbA1c) (MD = -0.24; 95% CI -0.49 to 0.00; p < 0.01) and high-density lipoprotein (MD = 0.07; 95% CI 0.01 to 0.12; p < 0.01). CONCLUSION Tai chi had better effects on metabolic control and body composition indicators than clinical conventional therapy, but only on HbA1c and HDL were superior than that of aerobic exercise. The best time-window for tai chi intervention may differ with different metabolic indices.
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Effect of SGLT inhibitors on weight and lipid metabolism at 24 weeks of treatment in patients with diabetes mellitus: A systematic review and network meta-analysis.
Chen, MB, Wang, H, Cui, WY, Xu, HL, Zheng, QH
Medicine. 2021;(6):e24593
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Abstract
BACKGROUND The goals of improving quality of life and increasing longevity are receiving growing amounts of attention. Body weight and lipid metabolism are closely related to various complications of diabetes. The aim of this study was to rank SGLT inhibitors according to their efficacy with regard to weight and evaluate the effect of SGLT inhibitors on lipid metabolism at 24 weeks of treatment. METHODS The Web of Science, PubMed, Cochrane Library, Embase, and Clinical Trials databases were electronically searched to collect randomized controlled trials involving patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the selected studies and extracted the outcome indexes. ADDIS 1.16.5 and STATA 16 software were used to perform the network meta-analysis and draw the plots. RESULTS Ultimately, 36 studies were selected and included in this study. We found that all SGLT inhibitors were effective at reducing weight; canagliflozin was the most effective. SGLT inhibitors and placebo were not associated with significantly different serum cholesterol levels. SGLT inhibitors lowered serum triglyceride levels and increased serum high-density and low-density lipoprotein cholesterol levels. SGLT inhibitors also reduced the level of alanine aminotransferase. CONCLUSIONS SGLT inhibitors can bring about weight loss in patients with T2DM and can also improve lipid metabolism. Therefore, patients with hyperlipidemia who have been unsuccessful at losing weight should consider taking SGLT inhibitors. In addition, SGLT inhibitors are hepatoprotective and appear to be safe for patients with mild to moderate liver dysfunction. TRIAL REGISTRATION CRD42020198516.
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Differences in the Effects of Anthocyanin Supplementation on Glucose and Lipid Metabolism According to the Structure of the Main Anthocyanin: A Meta-Analysis of Randomized Controlled Trials.
Araki, R, Yada, A, Ueda, H, Tominaga, K, Isoda, H
Nutrients. 2021;(6)
Abstract
The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): -0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: -0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.
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Genistein for glycolipid metabolism in postmenopausal women: a meta-analysis.
Yi, XY, Wang, ZH, Wang, Y
Climacteric : the journal of the International Menopause Society. 2021;(3):267-274
Abstract
OBJECTIVE This study aimed to evaluate the effects of genistein on glycolipid metabolism in postmenopausal women. METHODS Electronic databases were searched and relevant reports were hand-screened. We included only randomized controlled trials of isolated genistein for glycolipid metabolism. The primary outcome for lipid metabolism included a changed value of low-density lipoprotein cholesterol (LDL-C), and for glucose metabolism was a changed value of homeostasis model assessment for insulin resistance (HOMA-IR). Secondary outcomes included a changed value of total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), fasting blood insulin (INS), and body mass index (BMI). RESULTS Ten trials with 11 articles were included. The level of LDL-C was not decreased in the genistein group compared with the placebo group (standardized mean difference [SMD] = -0.58; 95% confidence interval [CI] - 1.19, 0.02; p = 0.06). No statistical significance was found in subgroup analyses. HOMA-IR was obviously improved in the genistein group with SMD of -0.51 (95% CI -0.88, -0.14; p = 0.006). In subgroup analyses, HOMA-IR was improved more in women with BMI <30 kg/m2 and without metabolic disorders (p < 0.0001). For secondary outcomes, there were significant differences in total cholesterol, HDL-C, FBG, and INS, but not triglyceride or BMI. CONCLUSIONS Genistein was effective in ameliorating glycolipid metabolism by increasing HDL-C levels and decreasing total cholesterol levels and improving insulin sensitivity.
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Effects of Statins on Lipid Profile of Kidney Transplant Recipients: A Meta-Analysis of Randomized Controlled Trials.
Huang, X, Jia, Y, Zhu, X, Zhang, Y, Jiang, L, Wei, X, Zhao, D, Zhao, X, Du, Y
BioMed research international. 2020;:9094543
Abstract
OBJECTIVE To assess the benefits of statins on lipid profile in kidney transplant recipients via a meta-analysis. METHODS We systematically identified peer-reviewed clinical trials, review articles, and treatment guidelines from PubMed, Embase, the Cochrane Library, Wanfang, Chinese National Knowledge Infrastructure (CNKI), SinoMed (CBM), and Chongqing VIP databases from inception to April 2019. In the analysis, only randomized controlled clinical trials performed in human were included. RESULTS Eight articles were included in the analysis, involving 335 kidney transplant recipients who received statins and 350 kidney transplant patients as the control group. Results revealed that statins improved the lipid profile of kidney transplant recipients. Specifically, statin therapy significantly reduced total cholesterol and low-density lipoprotein cholesterol. However, it had no effects on high-density lipoprotein cholesterol and triglyceride levels. CONCLUSIONS The present study provides valuable knowledge on the potential benefits of statins in kidney transplant recipients. This meta-analysis shows that statin therapy modifies the lipid profile in this patient population.
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Effect of Acute Caffeine Intake on the Fat Oxidation Rate during Exercise: A Systematic Review and Meta-Analysis.
Collado-Mateo, D, Lavín-Pérez, AM, Merellano-Navarro, E, Coso, JD
Nutrients. 2020;(12)
Abstract
A number of previous investigations have been designed to determine the effect of acute caffeine intake on the rate of fat oxidation during exercise. However, these investigations have shown contradictory results due to the differences in the exercise protocols used or the co-ingestion of caffeine with other substances. Hence, to date, there is no consensus about the effect of caffeine on fat oxidation during exercise. The purpose of this study was to conduct a systematic review followed by a meta-analysis to establish the effect of acute intake of caffeine (ranging from 2 to 7 mg/kg of body mass) on the rate of fat oxidation during exercise. A total of 19 studies published between 1978 and 2020 were included, all of which employed crossover experimental designs in which the ingestion of caffeine was compared to a placebo. Studies were selected if the exercise intensity was consistent in the caffeine and placebo trials and if these were preceded by a fasting protocol. A subsequent meta-analysis was performed using the random effects model to calculate the standardized mean difference (SMD). The meta-analysis revealed that caffeine significantly (p = 0.008) increased the fat oxidation rate (SMD = 0.73; 95% CI = 0.19 to 1.27). This increment was consistent with a significant (p = 0.04) reduction of the respiratory exchange ratio (SMD = -0.33; 95% CI = -0.65 to -0.01) and a significant (p = 0.049) increase in the oxygen uptake (SMD = 0.23; 95% CI = 0.01 to 0.44). The results also showed that there was a dose-response effect of caffeine on the fat oxidation rate, indicating that more than 3.0 mg/kg is necessary to obtain a statistically significant effect of this stimulant on fat oxidation during exercise. Additionally, the ability of caffeine to enhance fat oxidation during exercise was higher in sedentary or untrained individuals than in trained and recreational athletes. In conclusion, pre-exercise intake of a moderate dose of caffeine may effectively increase fat utilization during aerobic exercise of submaximal intensity performed after a fasting period. However, the fitness level of the participant may modulate the magnitude of the effect of caffeine on fat oxidation during exercise.
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Effect of evening primrose oil supplementation on lipid profile: A systematic review and meta-analysis of randomized clinical trials.
Khorshidi, M, Zarezadeh, M, Moradi Moghaddam, O, Emami, MR, Kord-Varkaneh, H, Mousavi, SM, Alizadeh, S, Heshmati, J, Olang, B, Aryaeian, N
Phytotherapy research : PTR. 2020;(10):2628-2638
Abstract
BACKGROUND Studies have shown that evening primrose oil (EPO) supplementation might be effective in improving lipid profile, however, the results are inconsistent. This study was performed to determine the direction and magnitude of the EPO effect on the lipid profile. METHODS PubMed, Scopus, Cochrane Library, Embase and Web of Science databases and Google Scholar were searched up to September-2019. Meta-analysis was performed using the random-effects model. Lipid profile including high-density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) was considered as the primary outcome. RESULTS A total of 926 articles were identified through database searching, of which, six RCTs were included in the meta-analysis. There were six studies on HDL, TC, and TG and four studies on LDL. EPO supplementation had no significant effect on TC, TG, LDL, and HDL. However, in subgroup analysis, a significant reduction in TG at a dose of ≤4 g/day (weighted mean difference [WMD] = -37.28 mg/dl; 95% CI: -73.53 to -1.03, p = .044) and a significant increase in HDL in hyperlipidemic subjects (WMD = 5.468 mg/dl; 95% CI: 1.323 to 9.614, p = .010) was found. CONCLUSION Oral intake of EPO at a dose of ≤4 g/day significantly reduces serum TG levels and significantly increases HDL levels in hyperlipidemic subjects.