RESUMEN
INTRODUCTION: Roux-en-Y gastric bypass (RYGB) substantially alters the gut microbial composition which could be associated with the metabolic improvements seen after surgery. Few studies have been conducted in Latin American populations, such as Mexico, where obesity prevalence is above 30% in the adult population. Thus, the aim of this study was to characterize the changes in the gut microbiota structure in a Mexican cohort before and after RYGB and to explore whether surgery-related changes in the microbial community were associated with weight loss. METHODS: Biological samples from patients who underwent RYGB were examined before and 12 months after surgery. Fecal microbiota characterization was performed through 16S rRNA sequencing. RESULTS: Twenty patients who underwent RYGB showed a median excess weight loss of 66.8% 12 months after surgery. Surgery increased alpha diversity estimates (Chao, Shannon index, and observed operational taxonomic units, p < 0.05) and significantly altered gut microbiota composition. Abundance of four genera was significantly increased after surgery: Oscillospira, Veillonella, Streptococcus, and an unclassified genus from Enterobacteriaceae family (PFDR < 0.1). The change in Veillonella abundance was associated with lower excess weight loss (rho = -0.446, p = 0.063) and its abundance post-surgery with a greater BMI (rho = 0.732, p = 5.4 × 10-4). In subjects without type 2 diabetes, lower bacterial richness and diversity before surgery were associated with a greater Veillonella increase after surgery (p < 0.05), suggesting that a lower bacterial richness before surgery could favor the bloom of certain oral-derived bacteria that could negatively impact weight loss. CONCLUSION: Presurgical microbiota profile may favor certain bacterial changes associated with less successful results.
Asunto(s)
Diabetes Mellitus Tipo 2 , Derivación Gástrica , Microbioma Gastrointestinal , Obesidad Mórbida , Adulto , Humanos , Derivación Gástrica/métodos , Obesidad Mórbida/cirugía , Obesidad Mórbida/microbiología , Estudios de Cohortes , ARN Ribosómico 16S/genética , Heces/microbiología , Bacterias/genética , Pérdida de PesoRESUMEN
Gut microbiota has been suggested to modulate circulating lipids. However, the relationship between the gut microbiota and atherogenic dyslipidemia (AD), defined as the presence of both low HDL-C and hypertriglyceridemia, is not fully understood. Moreover, because obesity is among the main causes of secondary AD, it is important to analyze the effect of gut microbiota composition on lipid profiles after a weight loss intervention. We compared the microbial diversity and taxonomic composition in patients with AD (n = 41) and controls (n = 38) and sought correlations of genera abundance with serum lipid levels in 20 patients after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Gut microbiota composition was profiled using next-generation sequencing of 16S rRNA. Gut microbiota diversity was significantly lower in atherogenic dyslipidemia. Moreover, relative abundance of two genera with LDA score >3.5 (Megasphaera and LPS-producing Escherichia-Shigella), was significantly higher in AD subjects, while the abundance of four short chain fatty acids (SCFA) producing-genera (Christensenellaceae R-7, Ruminococcaceae UCG-014; Akkermansia and [Eubacterium] eligens group) was significantly higher in controls. Notably, [Eubacterium] eligens group abundance was also significantly associated with higher HDL-C levels in RYGB patients one year after surgery. Although dietary polyunsaturated fatty acid/saturated fatty acid (PUFA/SFA) ratio and PUFA intake were higher in controls than in AD subjects, of the four genera differentiated in cases and controls, only Akkermansia abundance showed a positive and significant correlation with PUFA/SFA ratio. Our results suggest that SCFA-producing bacteria promote a healthy lipid homeostasis, while the presence of LPS-producing bacteria such Escherichia-Shigella may contribute to the development of atherogenic dyslipidemia.
Asunto(s)
Cirugía Bariátrica , Dislipidemias , Microbioma Gastrointestinal , Ácidos Grasos Volátiles , Humanos , Lipopolisacáridos , ARN Ribosómico 16S/genética , Pérdida de PesoRESUMEN
INTRODUCTION AND OBJECTIVES: Metabolic-associated fatty liver disease (MAFLD) is defined by steatosis in more than 5% of hepatocytes without other liver diseases. Patients with this disease can progress to multiple stages like liver fibrosis, cirrhosis, and hepatocellular carcinoma. miRNAs are single-stranded molecules that regulate metabolic homeostasis; their differential expression postulates them as potential circulating biomarkers for MAFLD. Previous research reported that hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p have a differential expression in patients with MAFLD. This study aimed to investigate the correlation between liver hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p and serum biomarkers CK-18, APOB, IL-6, IL-32, and TNF-α in patients with MAFLD compared with control patients. MATERIALS AND METHODS: A cross-sectional study was carried out with 16 patients of both sexes, aged between 18-60 years, to determine the association between the levels of hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p with MAFLD in liver biopsies of patients who underwent laparoscopic cholecystectomy. RESULTS: Twelve patients presented MAFLD, four without hepatic steatosis. Circulating levels of CK-18 showed a significant difference in patients with MAFLD, and a strong correlation was found between hsa-miR-122-3p, hsa-miR-140-5p, and hsa-miR-148b-5p versus the CAP value. CONCLUSION: There is a correlation between elevated tissue expression of hsa-miR-122-3p, hsa-miR-140-5p, and hsa-miR-148b-3p with plasma levels of CK-18 in patients with simple steatosis compared with patients without the disease.
Asunto(s)
Queratina-18 , MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Biomarcadores , Estudios Transversales , Queratina-18/genética , Hígado/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genéticaRESUMEN
We present a cohort of individuals who reached CD4+ T cell counts of greater than 1,000 cells/mm3 (Hypers) after starting antiretroviral treatment (ART) and compared them with those who reached between 350 and 999 CD4+ T cells/mm3 (Concordants). Demographic data, immune recovery kinetics, T CD4+ subset phenotypes, and integrated HIV DNA were analyzed. Data from individuals living with HIV on their first ART regimen and after 48 months of follow-up were obtained. Immune phenotype by Flow Cytometry analysis on whole blood was performed, cytokines were measured, and integrated HIV-1 DNA was measured by polymerase chain reaction. From a total of 424 individuals, 26 Hypers (6.1%), 314 Concordants (74.1%), and 84 (19.8%) discordants were identified. Hypers had a higher proportion of CD4+-naive (Nv) T cells (37.6 vs. 24.8, p < .05), and a low proportion of CD4+ effector memory T cells (27.9 vs. 39.4, p < .05), with similar results found in CD8+ T cells. Hypers demonstrated a higher percentage of CD4+CD45RA+CD31neg cells with a lower response to interleukin-2 stimulation and a lower integrated HIV-1 DNA/CD4 ratio (1.2 vs. 2.89, p < .05). In Hypers, T cell recovery occurs very early after initiation of ART. Following this initial recovery state, their CD4+ T cell level homeostasis seems to be driven by nonthymic-central-Nv cells. This exceptional recovery is associated with a lower HIV reservoir, which may be related to an increase in noninfected CD4+ T cells. These patients could then be eligible candidates for cure trials.
Asunto(s)
Linfocitos T CD8-positivos , Infecciones por VIH , Antirretrovirales/uso terapéutico , Linfocitos T CD4-Positivos , Diferenciación Celular , Infecciones por VIH/tratamiento farmacológico , HumanosRESUMEN
Vitamin D-binding protein (VDBP) is encoded by the GC gene and is an active participant in the control of bone metabolism. However, the effect of its major variants on VDBP concentration and bone mineral density (BMD) remains unclear. Our aim was to analyze the effect of major GC variants on serum VDBP concentration and BMD. We recruited individuals from the Health Workers Cohort Study, which includes employees of the Mexican Institute of Social Security (IMSS). A total of 1853 adults were included. The single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were genotyped to identify the three best characterized haplotypes of GC. Serum VBDP, 25(OH)D and BMD were also measured. Among women, the G allele of rs7041 was associated with higher VDBP and BMD compared to homozygous TT. The A allele of rs4588 was associated with lower VDBP and BMD compared to CC homozygous. In men, GC variants were only associated with VDBP levels. We did not observe an association between free/bioavailable 25(OH)D and BMD in men and women. Our results support an association of VDBP in bone health. The G and C alleles, from rs7041 and rs4588, respectively, are associated with high concentrations of VDBP and BMD in this sample of Mexican postmenopausal women.
Asunto(s)
Densidad Ósea , Proteína de Unión a Vitamina D/sangre , Femenino , Haplotipos , Homocigoto , Humanos , Masculino , México , Polimorfismo de Nucleótido Simple , Proteína de Unión a Vitamina D/genéticaRESUMEN
Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10-6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10-10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.
Asunto(s)
Indio Americano o Nativo de Alaska/genética , Acuaporina 4/genética , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Humanos , Masculino , México/epidemiologíaRESUMEN
Osteoporosis is a skeletal disease mainly affecting women over 50 years old and it represents a serious public health problem because of the high socioeconomic burden. This disease is characterized by deterioration of bone microarchitecture, low bone mineral density (BMD), and increased risk of fragility fractures. This study aimed to identify serum useful proteins as biomarkers for the diagnosis and/or prognosis of osteoporosis and fracture risk. We collected 446 serum samples from postmenopausal women aged ≥45 years old. Based on the BMD measurement, we classified the participants into three groups: osteoporotic, osteopenic, and normal. In an initial discovery stage, we conducted a proteomic approach using two-dimensional differential gel electrophoresis (2D-DIGE). The peptides into the spots of interest were identified through matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF/TOF). Enzyme-linked immunosorbent assay (ELISA) was performed to validate the proteins of interest. We identified 27 spots of interest when comparing low BMD versus normal BMD postmenopausal women. Based on their relevance in bone metabolism, we analyzed three proteins: ceruloplasmin (CP), gelsolin (GSN), and vitamin D-binding protein (VDBP). Our results demonstrated that low serum VDBP levels correlate with low BMD (osteopenic and osteoporotic). Therefore, VDBP could be considered as a novel, potential, and non-invasive biomarker for the early detection of osteoporosis.
Asunto(s)
Proteínas Sanguíneas/análisis , Densidad Ósea/fisiología , Osteoporosis Posmenopáusica/sangre , Proteoma/análisis , Proteína de Unión a Vitamina D/sangre , Biomarcadores/sangre , Femenino , Humanos , México , Persona de Mediana Edad , Posmenopausia/sangre , ProteómicaRESUMEN
While the effect of exercise on white adipose tissue browning and metabolic improvement in rodents is clear, there are few studies in humans with inconclusive results. Thus, the aim of the study was to assess whether an exercise intervention promotes subcutaneous adipose tissue browning in humans, and whether this response is associated with metabolic improvement in three groups of individuals defined by body mass index (BMI) (kg/m2). Sedentary adult subjects with different BMI were enrolled in a 12-week bicycle-training program (3 times per week, intensity 70-80% HRmax). Brown and beige gene expression in subcutaneous adipose tissue (scWAT) biopsies, and serum glucose, insulin, lipid, adipokine, and myokine levels were compared before and after the exercise intervention. Thirty-three non-diabetic subjects (mean age 30.4 ± 4.6 years; 57.57% female; 13 normal weight, 10 overweight and 10 with obesity) completed the exercise intervention. Without any significant change in body composition, exercise improved several metabolic parameters, most notably insulin resistance and particularly in the overweight group. Circulating adiponectin, apelin, and irisin exercise-induced changes predicted 60% of the insulin sensitivity improvement. After exercise UCP1, TBX1, CPT1B scWAT expression significantly increased, along with P2RX5 significant positive staining. These changes are compatible with scWAT browning, however, they were not associated with glucose metabolism improvement. In conclusion, 12-weeks of exercise training produced brown/beige gene expression changes in abdominal scWAT of non-diabetic individuals with different BMI, which did not contribute to the metabolic improvement. However, this result should not be interpreted as a lack of effect of browning on metabolic parameters. These findings suggest that a bigger effect is needed and should not preclude the development of more effective strategies of browning. Furthermore, exercise-induced changes in adiponectin, apelin, and irisin predicted insulin sensitivity improvement, supporting the important role of adipokines and myokines in metabolism homeostasis.
RESUMEN
BACKGROUND: The aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations. METHODS: A total of 3938 adults and 636 school-aged children from Central Mexico were genotyped for both polymorphisms. Subcutaneous and visceral adipose tissue biopsies from 22 class III obesity patients were analyzed for FTO and ABCA1 mRNA expression. Generalized linear models were used to test for associations and gene-gene interactions affecting BMI, WC and FTO expression. RESULTS: FTO and ABCA1 risk alleles were not individually associated with higher BMI or WC. However, in the absence of the ABCA1 risk allele, the FTO risk variant was significantly associated with higher BMI (P = 0.043) and marginally associated with higher WC (P = 0.067), as reported in Europeans. The gene-gene interaction affecting BMI and WC was statistically significant only in adults. FTO mRNA expression in subcutaneous abdominal adipose tissue according to ABCA1 genotype was consistent with these findings. CONCLUSIONS: This is the first report showing evidence of FTO and ABCA1 gene variant interactions affecting BMI, which may explain previously reported population differences. Further studies are needed to confirm this interaction.
Asunto(s)
Transportador 1 de Casete de Unión a ATP/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Índice de Masa Corporal , Epistasis Genética , Indígenas Norteamericanos/genética , Adulto , Niño , Femenino , Humanos , Masculino , MéxicoRESUMEN
OBJECTIVE: Irisin is a novel myokine that seems to mediate the beneficial effects of exercise. Levels of circulating irisin before and after an 8-month physical activity program (PAP) in school-age children were evaluated. METHODS: Irisin and leptin were measured at baseline and at follow-up among 85 children with different BMI. RESULTS: Of the 85 children (mean age 8.9; 47% female), 25 children had normal weight, 23 were overweight, and 37 had obesity. We observed no significant difference in irisin serum levels between boys and girls. Irisin was positively associated with BMI before and after the PAP (r(before) = 0.42; r(after) = 0.37, P < 0.001), with the highest levels in children with obesity. There was a slight decrease of circulating irisin after PAP, but this decrease was not of statistical significance. We observed a high and positive association between irisin and leptin levels before and after the PAP (r(before) = 0.78; r(after) = 0.82, P < 0.001). Moreover, changes in leptin correlated with changes in irisin (r = 0.72, P < 0.001). CONCLUSIONS: Circulating irisin is positively linked to BMI and leptin in school-age children, supporting the notion that that irisin is produced by adipose tissue. As in previous reports, this study failed to observe changes in irisin levels after exercise, likely because higher irisin levels are produced only during exercise.
Asunto(s)
Ejercicio Físico/fisiología , Fibronectinas/sangre , Leptina/sangre , Obesidad Infantil/metabolismo , Biomarcadores/sangre , Índice de Masa Corporal , Peso Corporal , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Obesidad Infantil/prevención & controlRESUMEN
The R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the Mexican mestizo population. However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. The aim of the present study was to analyze whether the effect of ABCA1-R230C on HDL-C concentrations is modulated by dietary factors in a nationwide population sample of 3591 adults from the National Health and Nutrition Survey conducted by the State's Employees' Social Security and Social Services Institute. All participants answered a validated questionnaire to assess health status and weekly food consumption. Fasting blood samples were drawn for biochemical analysis and DNA extraction, and the ABCA1-R230C variant was genotyped using TaqMan assays. Statistical analyses consisted of simple linear and multiple regression modeling adjusting for age, BMI, smoking, and alcohol consumption. The overall C risk allele frequency was 9.3% and the variant was significantly associated with low HDL-C concentrations in both sexes. A significant negative correlation between carbohydrate consumption and HDL-C concentrations was observed in women bearing the R230C variant (P = 0.021) and a significant gene-diet interaction was found only in premenopausal women (P = 0.037). In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , HDL-Colesterol/sangre , Carbohidratos de la Dieta/administración & dosificación , Variación Genética , Premenopausia , Transportador 1 de Casete de Unión a ATP , Adulto , Alelos , Estudios Transversales , Encuestas sobre Dietas , Carbohidratos de la Dieta/farmacología , Femenino , Genotipo , Humanos , Masculino , México , Persona de Mediana Edad , Premenopausia/sangre , Premenopausia/genética , Factores de Riesgo , Caracteres Sexuales , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To demonstrate whether patients undergoing capsulotomy Nd: YAG laser developed intraocular hypertension after the procedure. METHODS: Prospective, pre-experimental before and after 2 measurements with post-test in patients with posterior capsular opacity from the Ophthalmology Service. Measurements of intraocular pressure (IP) before capsulotomy Nd: YAG laser, and three hours and one week later. RESULTS: We studied 47 patients, 29.8 % were men and 70.2 % women. We compared between visual acuity before and one week later (Wilcoxon test p = 0.00). IP after three hours and one week later, comparisons with Friedman test were done (p =0. 002). We compared the IP prior and one week later (Wilcoxon test, with p =0.815). IP before and three hours later were obtained (p = 0.001) and IP three hours and one week later (p = 0.004). CONCLUSIONS: We found an increase in IP in the first hours after the capsulotomy Nd: YAG laser, which decrease gradually until reaching the values presented before the procedure, in not more than a week period. It is a quick and safe procedure to treat posterior capsular opacity.
Asunto(s)
Tuberculosis Pulmonar/diagnóstico , Adolescente , Adulto , Anciano , Niño , Estudios Transversales , Femenino , Humanos , Pruebas Inmunológicas , Masculino , Persona de Mediana Edad , Factores de Tiempo , Tuberculosis Pulmonar/sangre , Adulto JovenRESUMEN
OBJECTIVE: To compare the efficacy of efavirenz (EFV) vs lopinavir/ritonavir (LPV/r) in combination with azidothymidine/lamivudine in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4 counts <200/mm. METHODS: Prospective, randomized, open label, multicenter trial in Mexico. HIV-infected subjects with CD4 <200/mm were randomized to receive open label EFV or LPV/r plus azidothymidine/lamivudine (fixed-dose combination) for 48 weeks. Randomization was stratified by baseline CD4 cell count (< or =100 or >100/mm). The primary endpoint was the percentage of patients with plasma HIV-1 RNA <50 copies/mL at 48 weeks by intention-to-treat analysis. RESULTS: A total of 189 patients (85% men) were randomized to receive EFV (95) or LPV/r (94). Median baseline CD4 were 64 and 52/mm, respectively (P = not significant). At week 48, by intention-to-treat analysis, 70% of EFV and 53% of LPV/r patients achieved HIV-1 RNA <50 copies/mL [estimated difference 17% (95% confidence interval 3.5 to 31), P = 0.013]. The proportion with HIV-1 RNA <400 copies/mL was 73% with EFV and 65% with LPV/r (P = 0.25). Virologic failure occurred in 7 patients on EFV and 17 on LPV/r. Mean CD4 count increases (cells/mm) were 234 for EFV and 239 for LPV/r. Mean change in total cholesterol and triglyceride levels were 50 and 48 mg/dL in EFV and 63 and 116 mg/dL in LPV/r (P = 0.24 and P < 0.01). CONCLUSIONS: In these very advanced HIV-infected ARV-naive subjects, EFV-based highly active antiretroviral therapy had superior virologic efficacy than LPV/r-based highly active antiretroviral therapy, with a more favorable lipid profile.