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Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.
Montefusco, L, D'Addio, F, Loretelli, C, Ben Nasr, M, Garziano, M, Rossi, A, Pastore, I, Plebani, L, Lunati, ME, Bolla, AM, et al
Journal of endocrinological investigation. 2021;(11):2407-2415
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Abstract
BACKGROUND Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1β, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.
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Common genetic variation in obesity, lipid transfer genes and risk of Metabolic Syndrome: Results from IDEFICS/I.Family study and meta-analysis.
Nagrani, R, Foraita, R, Gianfagna, F, Iacoviello, L, Marild, S, Michels, N, Molnár, D, Moreno, L, Russo, P, Veidebaum, T, et al
Scientific reports. 2020;(1):7189
Abstract
As the prevalence of metabolic syndrome (MetS) in children and young adults is increasing, a better understanding of genetics that underlie MetS will provide critical insights into the origin of the disease. We examined associations of common genetic variants and repeated MetS score from early childhood to adolescence in a pan-European, prospective IDEFICS/I.Family cohort study with baseline survey and follow-up examinations after two and six years. We tested associations in 3067 children using a linear mixed model and confirmed the results with meta-analysis of identified SNPs. With a stringent Bonferroni adjustment for multiple comparisons we obtained significant associations(p < 1.4 × 10-4) for 5 SNPs, which were in high LD (r2 > 0.85) in the 16q12.2 non-coding intronic chromosomal region of FTO gene with strongest association observed for rs8050136 (effect size(β) = 0.31, pWald = 1.52 × 10-5). We also observed a strong association of rs708272 in CETP with increased HDL (p = 5.63 × 10-40) and decreased TRG (p = 9.60 × 10-5) levels. These findings along with meta-analysis advance etiologic understanding of childhood MetS, highlighting that genetic predisposition to MetS is largely driven by genes of obesity and lipid metabolism. Inclusion of the associated genetic variants in polygenic scores for MetS may prove to be fundamental for identifying children and subsequently adults of the high-risk group to allow earlier targeted interventions.
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Beneficial effect of CETP gene polymorphism in combination with a Mediterranean diet influencing lipid metabolism in metabolic syndrome patients: CORDIOPREV study.
Garcia-Rios, A, Alcala-Diaz, JF, Gomez-Delgado, F, Delgado-Lista, J, Marin, C, Leon-Acuña, A, Camargo, A, Rodriguez-Cantalejo, F, Blanco-Rojo, R, Quintana-Navarro, G, et al
Clinical nutrition (Edinburgh, Scotland). 2018;(1):229-234
Abstract
The cholesteryl ester transfer protein (CETP) gene has been implicated in high-density lipoprotein (HDL-C) metabolism. However, little is known about the impact of this gene on metabolic syndrome (MetS) patients and its interaction with diet. Here, we evaluate whether the consumption of a Mediterranean diet, compared with a Low-fat diet, interacts with the rs3764261 SNP at the CETP locus to modify lipid metabolism in MetS patients. Plasma lipid concentrations and rs3764261 genotypes were determined in 424 MetS subjects participating in the CORDIOPREV clinical trial (NCT00924937). Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% MUFA) vs Low-fat diet (28% fat, 12% MUFA)). We found significant gene-diet interactions between rs3764261 SNP and the dietary pattern for HDL-C (P = 0.006) and triglyceride concentrations (P = 0.040). Specifically, after 12 months of Mediterranean diet intervention, subjects who were carriers of the minor T allele (TT + TG) displayed higher plasma HDL-C concentrations (P = 0.021) and lower triglycerides (P = 0.020) compared with those who were homozygous for the major allele (GG). In contrast, in the Low-fat intervention group, no significant differences were found between CETP genotypes after 12 months of dietary treatment. Our data support the notion that the consumption of a Mediterranean diet may play a contributing role in triggering lipid metabolism by interacting with the rs3764261 SNP at CETP gene locus in MetS patients. Due to the complex nature of gene-environment interactions, dietary adjustment in MetS patients may require a personalized approach.
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Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome: Quantity vs quality over time and implication of CETP.
Chapman, MJ, Orsoni, A, Robillard, P, Therond, P, Giral, P
Journal of clinical lipidology. 2018;(3):784-800.e4
Abstract
BACKGROUND Statins impact the metabolism, concentrations, composition, and function of circulating lipoproteins. OBJECTIVE We evaluated time course relationships between statin-mediated reduction in atherogenic apolipoprotein B (ApoB)-containing particles and dynamic intravascular remodeling of ApoAI-containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome. METHODS Insulin-resistant, hypertriglyceridemic, hypercholesterolemic, obese males (n = 12) were treated with pitavastatin (4 mg/d) and response evaluated at 6, 42, and 180 days. RESULTS Reduction in low-density lipoprotein (LDL) cholesterol, ApoB, and triglycerides (TGs) was essentially complete at 42 days (-38%, -32%, and -35%, respectively); rapid reduction equally occurred in remnant cholesterol, ApoCII, CIII, and E levels (day 6; -35%, -50%, -23%, and -26%, respectively). Small dense LDLs (LDL4 and LDL5 subpopulations) predominated at baseline and were markedly reduced on treatment (-29% vs total LDL mass). Cholesteryl ester (CE) transfer protein activity and mass decreased progressively (-18% and -16%, respectively); concomitantly, TG depletion (up to -49%) and CE enrichment occurred in all high-density lipoprotein (HDL) particle subpopulations with normalization of CE/TG mass ratio at 180 days. ApoAI was redistributed from LpAI to LpAI:AII particles in HDL2a and HDL3a subpopulations; ApoCIII was preferentially depleted from LpAI:AII-rich particles on treatment. CONCLUSION Overall, statin action exhibits duality in mixed dyslipidemia, as CE transfer protein-mediated normalization of the HDL CE/TG core lags markedly behind subacute reduction in elevated levels of atherogenic ApoB-containing lipoproteins. Normalization of the HDL neutral lipid core is consistent with enhanced atheroprotective function. The HDL CE/TG ratio constitutes a metabolomic marker of perturbed HDL metabolism in insulin-resistant states, equally allowing monitoring of statin impact on HDL metabolism, structure, and function.
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Anacetrapib: a new weapon against dyslipidemia.
Aperis, G, Paliouras, C, Tsampikaki, E, Papakonstantinou, N, Alivanis, P
Current clinical pharmacology. 2011;(4):227-35
Abstract
Anacetrapib is a cholesteryl-ester-transfer-protein (CETP) inhibitor, a new class of experimental drugs in the treatment of primary hypercholesterolemia and dyslipidaemia associated with the metabolic syndrome. One of the major advantages of this agent is, apart from the significant decrease in LDL-C it produces a substantial increase in HDL-C. Phase I, II, and III clinical trials have shown that anacetrapib is safe alone or in combination with statins. However, longterm clinical trials are required in order to assess whether it reduces mortality in individuals at high-risk of cardiovascular disease.
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Indices of reverse cholesterol transport in subjects with metabolic syndrome after treatment with rosuvastatin.
Sviridov, D, Hoang, A, Ooi, E, Watts, G, Barrett, PH, Nestel, P
Atherosclerosis. 2008;(2):732-9
Abstract
OBJECTIVE The effects of the statin, rosuvastatin on indices of reverse cholesterol transport were studied in a randomized, placebo-controlled, cross-over trial in 25 overweight subjects with defined metabolic syndrome. RESULT Four weeks' treatment with 40 mg/day rosuvastatin significantly reduced levels of plasma cholesterol (44%), LDL cholesterol (60%) and triglyceride (38%). HDL cholesterol (mean [S.D.]) rose (0.97[0.17] to 1.05[0.17]mmol/L; P<0.05) and the LpA-I component of HDL from 39[7] to 45[9]mg/dL (P<0.05). LCAT activity fell (0.55[0.13] to 0.35[0.07]nmol/mL/h; P<0.05); CETP activity and mass fell from 89[13] to 80[11]nmol//L/h and from 1.66[0.57] to 1.28[0.41]mug/mL respectively, (P<0.05). Cholesterol efflux in vitro (to plasmas from THP-1 activated cells) fell from 7.1[1.8]% (placebo) to 6.2[1.7]% (rosuvastatin); P<0.05, but when plasmas depleted of apoB lipoproteins were studied, the difference in efflux was no longer statistically significant. During placebo efflux was paradoxically inversely correlated with HDL-C (P=0.016) and LpA-I (P=0.035) concentrations but these correlations were absent after rosuvastatin. CONCLUSIONS The data suggest possible HDL dysfunctionality in subjects with metabolic syndrome. The reduced capacity of plasmas following statin treatment to stimulate cholesterol efflux in vitro occurred in association with reduction in apoB lipoproteins and reduced activities of CETP and LCAT, and despite increased levels of HDL cholesterol.
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CETP TaqIB polymorphism in Turkish adults: association with dyslipidemia and metabolic syndrome.
Ozsait, B, Kömürcü Bayrak, E, Poda, M, Can, G, Hergenç, G, Onat, A, Humphries, SE, Erginel Unaltuna, N
Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology. 2008;(5):324-30
Abstract
OBJECTIVE In this study, our aim was to investigate the association of cholesterol ester transfer protein (CETP) TaqIB polymorphism with the likelihood of metabolic syndrome (MetS). METHODS Study was designed as a cross-sectional analysis of the Turkish Adult Risk Factor follow-up study. Randomly selected sample of 1585 persons were included in the analyses. Genomic DNAs were isolated and the genotyping was performed using TaqMan system. ANOVA, Chi-square, univariate analyses and logistic regression models were used to investigate the association of genotypes with clinical and biochemical measurements. RESULTS The frequencies of the B1B1, B1B2 and the B2B2 genotypes were 33.3%, 46.4% and 20.3%, respectively. The B2B2 genotype was associated with elevated high-density lipoprotein -cholesterol (HDL-C) levels (p<0.0001). After adjusting for sex and age B2B2 individuals had 15.9% higher HDL-C levels than B1B1 individuals. Furthermore, the likelihood of dyslipidemia was lower in the presence of the B2B2 genotype (30.9% non-dyslipidemic vs. 69.1% dyslipidemic, p=0.001) when compared to the other genotypes. Moreover, in a logistic regression model comprising age and environmental factors, B1 allele carriers showed higher odds ratios of 1.49 (OR=1.49, 95% CI; 1.03-2.14, p=0.032) for MetS only in females. CONCLUSIONS These results suggest that B1 allele is associated with MetS in adult females. However, TaqIB polymorphism appears not associated with the components of MetS other than atherogenic dyslipidemia in adult Turkish population.