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Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 A˃C, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study explored circulating miRNAs and target genes associated with metabolic syndrome (MetS) and cardiometabolic risk in obese patients. Small-RNA sequencing was used to assess the peripheral blood miRNome of 12 obese subjects (6 MetS and 6 non-MetS). Differentially expressed miRNAs and target genes were further analyzed by qPCR in a larger sample of obese patients (48 MetS and 32 non-MetS). miRNA:mRNA interactions were studied using in silico tools. miRNome analysis identified 10 downregulated miRNAs in MetS compared to non-Met patients ( p < 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta- CEBPB , KRAS proto-oncogene, GTPase- KRAS and suppressor of cytokine signaling 1- SOCS1 ) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and CEBPB mRNA levels were increased in MetS patients ( p < 0.05), and these effects were correlated with the number of MetS diagnostic criteria ( p < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high CEBPB expression, and serum hsCRP ( p < 0.05). miR-155 was negatively correlated with CEBPB , HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin ( p < 0.05). Downregulation of circulating miR-155 is associated with insulin resistance, poor glycemic control, and increased MetS-related cardiometabolic risk, and these effects are potentially mediated by interaction with CEBPB.

Aim: The influence of short-term add-on ezetimibe to simvastatin treatment on expression of adipokines and inflammatory markers was investigated in diabetic and nondiabetic patients with hypercholesterolemia., Method: Hypercholesterolemic nondiabetic (HC, n = 37) and diabetic (DM, n = 47) patients were treated with simvastatin (SV, 10 or 20 mg/d/8-wk) and then SV plus ezetimibe (SV + EZ, 10 mg each/d/4 wk). Serum lipids, glycemic profile, and inflammatory markers (hsCRP, adiponectin, resistin, VCAM-1, and ICAM-1) were evaluated before and after the add-on ezetimibe therapy. mRNA expression of ADIPOR1, ADIPOR2, RETN, VCAM1, and ICAM1 was measured by real-time PCR in peripheral blood mononuclear cells (PBMC)., Results: Serum concentrations of LDL and HDL cholesterol, and adiponectin were higher in HC than DM patients (P < .05). The add-on ezetimibe therapy reduced total and LDL cholesterol, apoB and adiponectin serum levels in HC and DM groups, and resistin in HC subjects (P < .05). DM patients showed higher expression of ADIPOR1, ADIPOR2, RETN, and VCAM1 in PBMC than subjects in HC group, before and after add-on ezetimibe therapy (P < .05). PBMC RETN mRNA expression was reduced by add-on ezetimibe therapy in HC individuals (P < .05), but not in DM subjects., Conclusion: Short-term add-on ezetimibe to simvastatin treatment suppressing effects on hypercholesterolemia and adiponectinemia is independent of the diabetes status. Resistin serum levels and leukocyte mRNA expression are influenced by add-on ezetimibe to statin treatment., (© 2017 John Wiley & Sons Ltd.)