Toll-like Receptor as a Molecular Link between Metabolic Syndrome and Inflammation: A Review

Metabolic Syndrome (MetS) involves a cluster of five conditions, i.e. obesity, hyperglycaemia, hypertension, hypertriglyceridemia and low High-Density Lipoprotein (HDL) cholesterol. All components of MetS share an underlying chronic inflammatory aetiology, manifested by increased levels of pro-inflammatory cytokines. The pathogenic role of inflammation in the development of MetS suggested that toll-like receptor (TLR) activation may trigger MetS. This review summarises the supporting evidence on the interactions between MetS and TLR activation, bridged by the elevation of TLR ligands during MetS. The regulatory circuits mediated by TLR activation, which modulates signal propagation, leading to the state of chronic inflammation, are also discussed. Taken together, TLR activation could be the molecular basis in the development of MetS-induced inflammation.

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Impact of the Level of Adherence to Mediterranean Diet on the Parameters of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Observational Studies

Nutrients ◽

10.3390/nu13051514 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1514

Author(s):

Dimitra Rafailia Bakaloudi ◽

Lydia Chrysoula ◽

Evangelia Kotzakioulafi ◽

Xenophon Theodoridis ◽

Michail Chourdakis

Keyword(s):

Metabolic Syndrome ◽

Mediterranean Diet ◽

Observational Studies ◽

Positive Impact ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Central Registry ◽

High Adherence ◽

The Impact

High adherence to the Mediterranean diet (MD) has been associated with a lower prevalence of Metabolic Syndrome (MetS). The present study aimed to investigate the impact of MD adherence on parameters of MetS. A systematic literature search was performed in PubMed, Cochrane Central Registry of Clinical Trials (CENTRAL), Scopus, EMBASE, Web of Science and Google Scholar databases. Observational studies that recorded adherence to MD and components/measures of the MetS, such as waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG), high-density lipoprotein (HDL) cholesterol and triglycerides (TG), were included in this study. A total of 58 studies were included in our study. WC and TG were significantly lower in the high adherence MD group (SMD: −0.20, (95%CI: −0.40, −0.01), SMD: −0.27 (95%CI: −0.27, −0.11), respectively), while HDL cholesterol was significantly higher in the same group (SMD: −0.28 (95%CI: 0.07, 0.50). There was no difference in FBG and SBP among the two groups (SMD: −0.21 (95%CI: −0.54, 0.12) & SMD: −0.15 (95%CI: −0.38, 0.07), respectively). MD may have a positive impact on all parameters of MetS. However, further research is needed in this field.

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Effect of the components of the metabolic syndrome on pulmonary function. The unexpected role of high-density lipoprotein cholesterol

Cirugía y Cirujanos (English Edition) ◽

10.24875/cirue.m18000025 ◽

2019 ◽

Vol 86 (2) ◽

Author(s):

Saúl Huerta-Ramírez ◽

Angélica Paniagua-Pérez ◽

David Castro-Serna ◽

Andrés Ledesma-Velázquez ◽

Alberto Rubio-Guerra ◽

...

Keyword(s):

Metabolic Syndrome ◽

Pulmonary Function ◽

High Density Lipoprotein ◽

High Density Lipoprotein Cholesterol ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

The Metabolic Syndrome

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Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

Acta Endocrinologica ◽

10.1530/eje-07-0451 ◽

2008 ◽

Vol 158 (1) ◽

pp. 53-60 ◽

Cited By ~ 29

Author(s):

Robin P F Dullaart ◽

Albert K Groen ◽

Geesje M Dallinga-Thie ◽

Rindert de Vries ◽

Wim J Sluiter ◽

...

Keyword(s):

Metabolic Syndrome ◽

High Density Lipoprotein ◽

Cholesterol Efflux ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Cholesterol Esterification ◽

Cellular Cholesterol ◽

Apo E ◽

Pltp Activity ◽

Cellular Cholesterol Efflux

ObjectiveWe tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol.DesignIn 76 subjects with and 94 subjects without MetS based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined plasma (apo)lipoproteins, pre-β-HDL formation, phospholipid transfer protein (PLTP) activity, cholesterol esterification (EST), cholesteryl ester transfer (CET), adiponectin, and the ability of plasma from each subject to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single donor.ResultsApo E, PLTP activity, EST, and CET were higher (P=0.04 to <0.001), whereas adiponectin was lower in MetS subjects (P<0.01). Pre-β-HDL and pre-β-HDL formation were not different between subjects with and without MetS. Cellular cholesterol efflux to plasma from MetS subjects was slightly higher versus plasma from subjects without MetS (8.8±1.0 vs 8.5±0.9%,P=0.05), but the difference was not significant after age, sex, and diabetes adjustment. Cellular cholesterol efflux was positively related to pre-β-HDL formation, EST, PLTP activity, and apo E (P<0.05 for all by multiple linear regression analysis), without an independent association with MetS and diabetes status.ConclusionsThe ability of plasma from MetS subjects to promote fibroblast cholesterol efflux is not defective, although HDL cholesterol is decreased. Higher cholesterol esterification, PLTP activity, and apo E levels may contribute to the maintenance of cholesterol efflux in MetS.

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Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism

Scientific Reports ◽

10.1038/s41598-019-51367-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Kenji Nishimura ◽

Taichi Murakami ◽

Toshihiro Sakurai ◽

Masashi Miyoshi ◽

Kiyoe Kurahashi ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Insulin Resistant ◽

Cell Dysfunction ◽

Fractionation Analysis ◽

Abnormal Lipid Metabolism ◽

Hdl Metabolism ◽

Relationship Of

Abstract Circulating ApolipoproteinL1 (ApoL1) is a component of pre-β-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = −0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with β cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.

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Comparing the validity of continuous metabolic syndrome risk scores for predicting pediatric metabolic syndrome: the CASPIAN-V study

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0384 ◽

2019 ◽

Vol 32 (4) ◽

pp. 383-389 ◽

Cited By ~ 1

Author(s):

Mehri Khoshhali ◽

Ramin Heshmat ◽

Mohammad Esmaeil Motlagh ◽

Hasan Ziaodini ◽

Mahdi Hadian ◽

...

Keyword(s):

Metabolic Syndrome ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Principal Component ◽

Hdl Cholesterol ◽

Cross Sectional Study ◽

Risk Scores ◽

Cross Sectional ◽

Z Scores ◽

Iranian Children

Abstract Background The aim of this study was to compare the validity of various approaches to pediatric continuous metabolic syndrome (cMetS) scores including siMS scores (2 waist/height + fasting blood glucose [FBG]/5.6 + triglycerides [TG]/1.7 + systolic blood pressure [BP]/130 + high-density lipoprotein [HDL]/1.02), Z-scores, principal component analysis (PCA) and confirmatory factor analysis (CFA) for predicting metabolic syndrome (MetS). Methods This nationwide cross-sectional study was conducted on 4200 Iranian children and adolescents aged 7–18 years. The cMetS was computed using data on HDL, cholesterol, TGs, FBG, mean arterial pressure (MAP) and waist circumference (WC). The areas under the receiver operating characteristic curves (AUCs) were used to compare the performances of different cMetS scores. Results Data of 3843 participants (52.4% boys) were available for the current study. The mean (standard deviation [SD]) age was 12.6 (3) and 12.3 (3.1) years for boys and girls, respectively. The differences in AUC values of cMetS scores were significant based on the Delong method. The AUCs (95% confidence interval [CI]) were for Z-scores, 0.94 (0.93, 0.95); first PCA, 0.91 (0.89, 0.93); sum PCA, 0.90 (0.88, 0.92), CFA, 0.79 (0.76, 0.3) and also for siMS scores 1 to 3 as 0.93 (0.91, 0.94), 0.92 (0.90, 0.93), and 0.91 (0.90, 0.93), respectively. Conclusions The results of our study indicated that the validity of all approaches for cMetS scores for predicting MetS was high. Given that the siMS scores are simple and practical, it might be used in clinical and research practice.

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Metabolic Syndrome—Role of Dietary Fat Type and Quantity

Nutrients ◽

10.3390/nu11071438 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1438 ◽

Cited By ~ 7

Author(s):

Peter Clifton

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Dietary Fat ◽

Saturated Fat ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Fasting Insulin ◽

Polyunsaturated Fat ◽

Monounsaturated Fat ◽

The Impact

Background: Metabolic syndrome increases the risk of cardiovascular disease (CVD) over and above that related to type 2 diabetes. The optimal diet for the treatment of metabolic syndrome is not clear. Materials and Methods: A review of dietary interventions in volunteers with metabolic syndrome as well as studies examining the impact of dietary fat on the separate components of metabolic syndrome was undertaken using only recent meta-analyses, if available. Results: Most of the data suggest that replacing carbohydrates with any fat, but particularly polyunsaturated fat, will lower triglyceride(TG), increase high density lipoprotein (HDL) cholesterol, and lower blood pressure, but have no effects on fasting glucose in normal volunteers or insulin sensitivity, as assessed by euglycemic hyperinsulinemic clamps. Fasting insulin may be lowered by fat. Monounsaturated fat (MUFA) is preferable to polyunsaturated fat (PUFA) for fasting insulin and glucose lowering. The addition of 3–4 g of N3 fats will lower TG and blood pressure (BP) and reduce the proportion of subjects with metabolic syndrome. Dairy fat (50% saturated fat) is also related to a lower incidence of metabolic syndrome in cohort studies.

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Prospective Study of Sex-Specific Adiponectin Changes and Incident Metabolic Syndrome: The ARIRANG Study

Journal of Clinical Medicine ◽

10.3390/jcm8050599 ◽

2019 ◽

Vol 8 (5) ◽

pp. 599

Author(s):

Ji Hye Huh ◽

Tae Woong Yoon ◽

Dae Ryong Kang ◽

Jang Young Kim

Keyword(s):

Metabolic Syndrome ◽

Prospective Study ◽

Adiponectin Level ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Population Based ◽

Clinical Role ◽

High Baseline ◽

The Individual

We investigated whether changes in adiponectin levels over time predict incident metabolic syndrome (MetS) in a population-based prospective study. In total, 1110 subjects were categorized into four groups according to their sex-specific median baseline adiponectin levels and the change in adiponectin levels at follow-up: low baseline adiponectin and decreased adiponectin during follow-up (LB&DF), low baseline adiponectin and increased adiponectin during follow-up (LB&IF), high baseline adiponectin and decreased adiponectin during follow-up (HB&DF), and high baseline adiponectin and increased adiponectin during follow-up (HB&IF). During the median 2.4-year follow-up period, 180 (16.2%) subjects developed MetS. Compared to the LB&DF group, the fully adjusted hazard ratio (95% confidence interval) for incident MS was the lowest in the HB&IF group (0.33, (0.17–0.63)), followed by the HB&DF group (0.58, (0.40–0.84)) and LB&IF group (0.63, (0.41–0.93)). This phenomenon was more prominent in men than in women. Among the individual MetS components, increased adiponectin levels during follow-up were significantly associated with lower risks of incident low high density lipoprotein (HDL) cholesterol and incident high blood pressure. This finding suggests that a change in adiponectin level, as well as the baseline adiponectin level, might have a clinical role in the development of MetS among men.

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Novel Insights From Human Studies on the Role of High-Density Lipoprotein in Mortality and Noncardiovascular Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.314050 ◽

2020 ◽

Author(s):

Christian M. Madsen ◽

Anette Varbo ◽

Børge G. Nordestgaard

Keyword(s):

Cardiovascular Disease ◽

High Density Lipoprotein ◽

Therapeutic Potential ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Cancer Type ◽

Health And Disease ◽

And Function

The vast majority of research about HDL (high-density lipoprotein) has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within cardiovascular disease prevention; however, failures with therapies aimed at increasing HDL cholesterol has left questions as to what the role and function of HDL in human health and disease is. Recent observational studies have further shown that extreme high HDL cholesterol is associated with high mortality leading to speculations that HDL could in some instances be harmful. In addition, evidence from observational, and to a lesser extent genetic, studies has emerged indicating that HDL might be associated with the development of other major noncardiovascular diseases, such as infectious disease, autoimmune disease, cancer, type 2 diabetes, kidney disease, and lung disease. In this review, we discuss (1) the association between extreme high HDL cholesterol and mortality and (2) the emerging human evidence linking HDL to several major diseases outside the realm of cardiovascular disease.

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