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1.
Int J Mol Sci ; 24(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37175691

RESUMO

Obesity causes systemic inflammation, hepatic and renal damage, as well as gut microbiota dysbiosis. Alternative vegetable sources rich in polyphenols are known to prevent or delay the progression of metabolic abnormalities during obesity. Vachellia farnesiana (VF) is a potent source of polyphenols with antioxidant and anti-inflammatory activities with potential anti-obesity effects. We performed an in vivo preventive or an interventional experimental study in mice and in vitro experiments with different cell types. In the preventive study, male C57BL/6 mice were fed with a Control diet, a high-fat diet, or a high-fat diet containing either 0.1% methyl gallate, 10% powdered VFP, or 0.5%, 1%, or 2% of a polyphenolic extract (PE) derived from VFP (Vachellia farnesiana pods) for 14 weeks. In the intervention study, two groups of mice were fed for 14 weeks with a high-fat diet and then one switched to a high-fat diet with 10% powdered VFP for ten additional weeks. In the in vitro studies, we evaluated the effect of a VFPE (Vachellia farnesiana polyphenolic extract) on glucose-stimulated insulin secretion in INS-1E cells or of naringenin or methyl gallate on mitochondrial activity in primary hepatocytes and C2C12 myotubes. VFP or a VFPE increased whole-body energy expenditure and mitochondrial activity in skeletal muscle; prevented insulin resistance, hepatic steatosis, and kidney damage; exerted immunomodulatory effects; and reshaped fecal gut microbiota composition in mice fed a high-fat diet. VFPE decreased insulin secretion in INS-1E cells, and its isolated compounds naringenin and methyl gallate increased mitochondrial activity in primary hepatocytes and C2C12 myotubes. In conclusion VFP or a VFPE prevented systemic inflammation, insulin resistance, and hepatic and renal damage in mice fed a high-fat diet associated with increased energy expenditure, improved mitochondrial function, and reduction in insulin secretion.


Assuntos
Dieta Hiperlipídica , Resistência à Insulina , Masculino , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Prebióticos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Inflamação/tratamento farmacológico
2.
Medicina (Kaunas) ; 59(10)2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37893503

RESUMO

Background and Objectives: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity. Materials and Methods: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. Liver steatosis and fibrosis were estimated using transient elastography (Fibroscan® Echosens, Paris, France). Three groups were studied: a non-MASLD group, an MASLD group, and a group for MASLD + fibrosis. A partial least squares discriminant analysis (PLS-DA) was performed to identify the discrimination between the study groups and to visualize the differences between their heatmaps; also, Variable Importance Projection (VIP) plots were graphed. A VIP score of >1.5 was considered to establish the importance of metabolites and biochemical parameters that characterized each group. Logistic regression models were constructed considering VIP scores of >1.5, and the receiver operating characteristic (ROC) curves were estimated to evaluate different combinations of variables. Results: The metabolic MASLD phenotype was associated with increased concentrations of ALT and decreased arginine, glycine, and acylcarnitine (AC) AC5:1, while MASLD + fibrosis, an advanced stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. Conclusions: The metabolic MASLD phenotype changes as this metabolic dysfunction progresses. Understanding metabolic disturbances in MASLD would allow for early identification and the development of intervention strategies focused on limiting the progression of liver damage in children and adolescents.


Assuntos
Fígado Gorduroso , Adolescente , Humanos , Criança , Estudos Transversais , Obesidade/complicações , Cirrose Hepática/complicações , Fenótipo
3.
Br J Nutr ; 128(1): 43-54, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34340727

RESUMO

Branched-chain amino acids (BCAA) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of the SNP of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAA in subjects with obesity and IR. A prospective cohort study of adult subjects with obesity, BMI ≥ 30 kg/m2, homeostatic model assessment-insulin resistance (HOMA-IR ≥ 2·5) no diagnosed chronic disease, underwent a DI with an energy restriction of 3140 kJ/d and nutritional education for 1 month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure, oral glucose tolerance test results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNP were assessed by the TaqMan SNP genotyping assay. A total of eighty-two subjects were included, and fifteen subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine and the sum of BCAA. Those subjects also had a greater reduction in skeletal muscle mass, fat-free mass, total body water, blood pressure, muscle strength and biochemical parameters after 1 month of the DI and adjusting for age and sex. This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a 1-month energy-restricted DI.


Assuntos
Resistência à Insulina , Proteínas da Gravidez , Adulto , Humanos , Estudos Prospectivos , Glicemia/metabolismo , Aminoácidos de Cadeia Ramificada , Obesidade/metabolismo , Transaminases/genética , Proteínas da Gravidez/genética , Antígenos de Histocompatibilidade Menor
4.
Mol Med ; 27(1): 50, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030623

RESUMO

OBJECTIVE: To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. METHODS: Hypervariable V3-V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profiles using bioinformatics in order to identify differences in taxonomy and metabolic pathways. RESULTS: We identified a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifidobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabolism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed differences in key bacterial enzymes involved in urate synthesis, degradation, and elimination. CONCLUSION: Our findings revealed that taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.


Assuntos
Disbiose , Microbioma Gastrointestinal , Gota/metabolismo , Metagenoma , Metagenômica , Ácido Úrico/metabolismo , Biodiversidade , Biologia Computacional/métodos , Gota/etiologia , Gota/patologia , Humanos , Metagenômica/métodos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas
5.
Eur J Nutr ; 60(5): 2435-2447, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33145643

RESUMO

PURPOSE: We compared the effect of diets with different amounts and sources of dietary protein on insulin sensitivity (IS) in subjects with obesity and insulin resistance (IR). METHODS: Eighty subjects with obesity (BMI ≥ 30 kg/m2) and IR (Matsuda index < 4.3 and HOMA-IR ≥ 2.5) over 18 years old were randomized to four groups for a one-month period: a normal protein diet (< 20%) with a predominance of animal protein (Animal NP) or vegetable protein (Vegetable NP) and a high-protein diet (25-30%) with a predominance of animal protein (Animal HP) or vegetable protein (Vegetable HP). Baseline and final measurements of body weight, body composition, biochemical parameters, blood pressure (BP), resting energy expenditure and plasma amino acid profiles were performed. RESULTS: Body weight, BMI and waist circumference decreased in all groups. Interestingly, the IS improved more in the Animal HP (Matsuda index; 1.39 vs 2.58, P = 0.003) and in the Vegetable HP groups (Matsuda index; 1.44 vs 3.14, P < 0.0001) after one month. The fat mass, triglyceride levels, C-reactive protein levels and the leptin/adiponectin index decreased; while, the skeletal muscle mass increased in the Animal and Vegetable HP groups. The BP decreased in all groups except the Animal NP group. CONCLUSION: Our study demonstrates that a high-protein hypocaloric diets improves IS by 60-90% after one month in subjects with obesity and IR, regardless of weight loss and the source of protein, either animal or vegetable. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03627104), August 13, 2018.


Assuntos
Resistência à Insulina , Adolescente , Índice de Massa Corporal , Dieta Redutora , Proteínas Alimentares , Humanos , Obesidade , Redução de Peso
6.
Nutr Metab Cardiovasc Dis ; 31(11): 3210-3218, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34511290

RESUMO

BACKGROUND AND AIM: Circulating amino acids are modified by sex, body mass index (BMI) and insulin resistance (IR). However, whether the presence of genetic variants in branched-chain amino acid (BCAA) catabolic enzymes modifies circulating amino acids is still unknown. Thus, we determined the frequency of two genetic variants, one in the branched-chain aminotransferase 2 (BCAT2) gene (rs11548193), and one in the branched-chain ketoacid dehydrogenase (BCKDH) gene (rs45500792), and elucidated their impact on circulating amino acid levels together with clinical, anthropometric and biochemical parameters. METHODS AND RESULTS: We performed a cross-sectional comparative study in which we recruited 1612 young adults (749 women and 863 men) aged 19.7 ± 2.1 years and with a BMI of 24.9 ± 4.7 kg/m2. Participants underwent clinical evaluation and provided blood samples for DNA extraction and biochemical analysis. The single nucleotide polymorphisms (SNPs) were determined by allelic discrimination using real-time polymerase chain reaction (PCR). The frequencies of the less common alleles were 15.2 % for BCAT2 and 9.83 % for BCKDH. The subjects with either the BCAT2 or BCKDH SNPs displayed no differences in the evaluated parameters compared with subjects homozygotes for the most common allele at each SNP. However, subjects with both SNPs had higher body weight, BMI, blood pressure, glucose, and circulating levels of aspartate, isoleucine, methionine, and proline than the subjects homozygotes for the most common allele (P < 0.05, One-way ANOVA). CONCLUSION: Our findings suggest that the joint presence of both the BCAT2 rs11548193 and BCKDH rs45500792 SNPs induces metabolic alterations that are not observed in subjects without either SNP.


Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/genética , Aminoácidos/sangue , Antígenos de Histocompatibilidade Menor/genética , Polimorfismo de Nucleotídeo Único , Proteínas da Gravidez/genética , Transaminases/genética , 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/metabolismo , Adolescente , Fatores Etários , Biomarcadores/sangue , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Homozigoto , Humanos , Masculino , México , Antígenos de Histocompatibilidade Menor/metabolismo , Fenótipo , Proteínas da Gravidez/metabolismo , Transaminases/metabolismo , Adulto Jovem
7.
Gynecol Obstet Invest ; 85(3): 277-283, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32320981

RESUMO

INTRODUCTION: The existence of a placental microbiome would require a non-antagonistic relationship between potentially colonizing bacteria and trophoblasts. OBJECTIVE: The immunologic response of trophoblasts to specific potentially invading bacteria needs further analysis. METHODOLOGY: Immortalized first trimester human trophoblasts Swan 71 (Sw.71) were coincubated with Escherichia coli, Lactobacillus jensenii, Lactobacillus crispatus, and incubated alone (i.e., control group; 4 conditions with n = 6 for each condition). Chemokines and cytokines were measured. ANOVA with post hoc pairwise analysis was used to compare cytokines/chemokines concentrations in the 4 culture media. RESULTS: Sw.71 co-incubated with E. coli, L. jensenii or L. crispatus resulted in differential secretion of 11 of the 26 assayed cytokines/chemokines. Sw.71 co-incubated with any of the 3 bacteria responded with significant increased secretion of interleukin (IL)-8 and granulocyte macrophage colony-stimulating factor. All bacteria elicited the secretion of IL-6 and interferon (IFN) α2, 2 proinflammatory cytokines. In addition, Lactobacillus species resulted in increased secretion of IL-12p40 and IFNγ. While E. coli did not modify secretion of anti-inflammatory cytokines, Sw.71 cells responded to co-incubation with Lactobacillus species by secreting increased levels of IL-10 and IL-1ra. Both Lactobacillus species led to a decreased secretion of IL-4. CONCLUSION: All 3 bacterial species triggered significant release of chemokines and inflammatory cytokines, suggesting that a commensal relationship with trophoblasts may not be feasible.


Assuntos
Quimiocinas/metabolismo , Citocinas/metabolismo , Escherichia coli , Lactobacillus crispatus , Lactobacillus , Trofoblastos/imunologia , Secreções Corporais , Técnicas de Cultura de Células , Feminino , Humanos , Placenta/citologia , Placenta/microbiologia , Gravidez , Primeiro Trimestre da Gravidez/imunologia
8.
Rev Invest Clin ; 70(2): 96-102, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29718011

RESUMO

BACKGROUND: It has been proposed that abnormal modulation of inflammatory response is involved in the physiopathology of idiopathic recurrent spontaneous abortion (iRSA). Factors that may participate in this process include the genetic background such as carrying specific polymorphisms of genes with functional effects. OBJECTIVE: The objective is to study the association between iRSA and the frequency of intron-2 variable number tandem repeat-polymorphisms of interleukin-1 receptor antagonist gene (IL1RN). METHODS: We conducted a case-control study including 108 women with iRSA and 103 controls. Five allelic variants of IL1RN were determined by polymerase chain reaction (PCR) product length analysis. RESULTS: The most frequent IL1RN allele in this population was IL1RN*1, which was present in 78% of cases and 94% of controls, and allele IL1RN*2, in 45 (20.8%) cases and 12 (5.8%) controls. Allele IL1RN*2 was significantly associated with iRSA (odds ratio = 4.28, 95% confidence interval 2.2-8.4; p = 0.000). CONCLUSION: Carrying allele IL1RN*2 had a strong association with iRSA in Mexican women. This polymorphism codifies for a low-function protein, which may allow for increased activity of IL-1 pro-inflammatory axis in iRSA.


Assuntos
Aborto Habitual/genética , Predisposição Genética para Doença , Proteína Antagonista do Receptor de Interleucina 1/genética , Íntrons/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Humanos , México , Pessoa de Meia-Idade , Repetições Minissatélites , Reação em Cadeia da Polimerase , Polimorfismo Genético , Gravidez , Adulto Jovem
9.
Biochim Biophys Acta ; 1841(1): 132-40, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24013029

RESUMO

Obesity is a public health problem that contributes to the development of insulin resistance, which is associated with an excessive accumulation of lipids in skeletal muscle tissue. There is evidence that soy protein can decrease the ectopic accumulation of lipids and improves insulin sensitivity; however, it is unknown whether soy isoflavones, particularly genistein, can stimulate fatty acid oxidation in the skeletal muscle. Thus, we studied the mechanism by which genistein stimulates fatty acid oxidation in the skeletal muscle. We showed that genistein induced the expression of genes of fatty acid oxidation in the skeletal muscle of Zucker fa/fa rats and in leptin receptor (ObR)-silenced C2C12 myotubes through AMPK phosphorylation. Furthermore, the genistein-mediated AMPK phosphorylation occurred via JAK2, which was possibly activated through a mechanism that involved cAMP. Additionally, the genistein-mediated induction of fatty acid oxidation genes involved PGC1α and PPARδ. As a result, we observed that genistein increased fatty acid oxidation in both the control and silenced C2C12 myotubes, as well as a decrease in the RER in mice, suggesting that genistein can be used in strategies to decrease lipid accumulation in the skeletal muscle.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Anticarcinógenos/farmacologia , Ácidos Graxos/metabolismo , Genisteína/farmacologia , Janus Quinase 2/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Mioblastos Esqueléticos/metabolismo , Receptores para Leptina/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Ácidos Graxos/genética , Janus Quinase 2/genética , Masculino , Camundongos , Oxirredução/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fosforilação/efeitos dos fármacos , Ratos , Ratos Zucker , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores para Leptina/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
Br J Nutr ; 111(12): 2059-66, 2014 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-24666631

RESUMO

Several studies using different animal models have demonstrated that the consumption of soya protein (SP) reduces serum cholesterol concentrations by increasing the excretion of bile acids (BA). However, the mechanism by which SP enhances BA excretion is not fully understood. Therefore, the aim of the present study was to determine whether the consumption of SP regulates the expression of key enzymes involved in hepatic BA synthesis and the transporters involved in reverse cholesterol transport (RCT) via fibroblast growth factor 15 (FGF15) and/or small heterodimer protein (SHP) in rats. To achieve this aim, four groups of rats were fed experimental diets containing 20 % casein (C) or SP with or without the addition of 0·2 % cholesterol and the expression of hepatic genes involved in BA synthesis and the ileal and hepatic RCT was measured. Rats fed the SP diet had higher concentrations of ileal FGF15 and hepatic FGF15 receptor (FGFR4) and increased expression of SHP and liver receptor homolog 1 (LRH1) than those fed the C diet; as a result, the excretion of faecal BA was greater. The addition of cholesterol to the diet repressed the protein abundance of FGF15 and FGFR4; however, SP increased the expression of SHP and LRH1 to a lesser extent. Nonetheless, the expression of ABCG5/8 was increased in the intestine of rats fed the SP diet, and the effect was enhanced by the addition of cholesterol to the diet. In conclusion, SP in the presence of cholesterol increases BA synthesis via the repressions of FGF15 and SHP and accelerates BA excretion to prevent cholesterol overload in the enterocytes by increasing RCT.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colagogos e Coleréticos/metabolismo , Colesterol na Dieta/metabolismo , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Proteínas de Vegetais Comestíveis/metabolismo , Proteínas de Soja/metabolismo , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Anticolesterolemiantes/metabolismo , Ácidos e Sais Biliares/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Íleo/metabolismo , Lipoproteínas/genética , Lipoproteínas/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Regulação para Cima
11.
Br J Nutr ; 112(6): 886-99, 2014 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-25201301

RESUMO

Black bean (Phaseolus vulgaris L.) seed coats are a rich source of natural compounds with potential beneficial effects on human health. Beans exert hypolipidaemic activity; however, this effect has not been attributed to any particular component, and the underlying mechanisms of action and protein targets remain unknown. The aim of the present study was to identify and quantify primary saponins and flavonoids extracted from black bean seed coats, and to study their effects on lipid metabolism in primary rat hepatocytes and C57BL/6 mice. The methanol extract of black bean seed coats, characterised by a HPLC system with a UV-visible detector and an evaporative light-scattering detector and HPLC-time-of-flight/MS, contained quercetin 3-O-glucoside and soyasaponin Af as the primary flavonoid and saponin, respectively. The extract significantly reduced the expression of SREBP1c, FAS and HMGCR, and stimulated the expression of the reverse cholesterol transporters ABCG5/ABCG8 and CYP7A1 in the liver. In addition, there was an increase in the expression of hepatic PPAR-α. Consequently, there was a decrease in hepatic lipid depots and a significant increase in bile acid secretion. Furthermore, the ingestion of this extract modulated the proportion of lipids that was used as a substrate for energy generation. Thus, the results suggest that the extract of black bean seed coats may decrease hepatic lipogenesis and stimulate cholesterol excretion, in part, via bile acid synthesis.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Suplementos Nutricionais , Flavonoides/uso terapêutico , Lipotrópicos/uso terapêutico , Phaseolus/química , Saponinas/uso terapêutico , Sementes/química , Animais , Ácidos e Sais Biliares/metabolismo , Células Cultivadas , Colagogos e Coleréticos/química , Colagogos e Coleréticos/isolamento & purificação , Colagogos e Coleréticos/metabolismo , Colesterol/metabolismo , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/metabolismo , Regulação da Expressão Gênica , Hepatócitos/citologia , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Metabolismo dos Lipídeos , Lipotrópicos/química , Lipotrópicos/isolamento & purificação , Lipotrópicos/metabolismo , Receptores X do Fígado , Masculino , México , Camundongos , Camundongos Endogâmicos C57BL , Receptores Nucleares Órfãos/agonistas , Receptores Nucleares Órfãos/genética , Receptores Nucleares Órfãos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico , Distribuição Aleatória , Ratos , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/metabolismo
12.
Cytokine Growth Factor Rev ; 76: 86-98, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38233286

RESUMO

Cell-to-cell communication mediated by Extracellular Vesicles (EVs) is a novel and emerging area of research, especially during pregnancy, in which placenta derived EVs can facilitate the feto-maternal communication. EVs comprise a heterogeneous group of vesicle sub-populations with diverse physical and biochemical characteristics and originate by specific biogenesis mechanisms. EVs transfer molecular cargo (including proteins, nucleic acids, and lipids) between cells and are critical mediators of cell communication. There is growing interest among researchers to explore into the molecular cargo of EVs and their functions in a physiological and pathological context. For example, inflammatory mediators such as cytokines are shown to be released in EVs and EVs derived from immune cells play key roles in mediating the immune response as well as immunoregulatory pathways. Pregnancy complications such as gestational diabetes mellitus, preeclampsia, intrauterine growth restriction and preterm birth are associated with altered levels of circulating EVs, with differential EV cargo and bioactivity in target cells. This implicates the intriguing roles of EVs in reprogramming the maternal physiology during pregnancy. Moreover, the capacity of EVs to carry bioactive molecules makes them a promising tool for biomarker development and targeted therapies in pregnancy complications. This review summarizes the physiological and pathological roles played by EVs in pregnancy and pregnancy-related disorders and describes the potential of EVs to be translated into clinical applications in the diagnosis and treatment of pregnancy complications.


Assuntos
Vesículas Extracelulares , Pré-Eclâmpsia , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Nascimento Prematuro/metabolismo , Nascimento Prematuro/patologia , Vesículas Extracelulares/fisiologia , Comunicação Celular
13.
PLoS One ; 19(5): e0302726, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38743706

RESUMO

BACKGROUND: Dysbiosis during childhood impacts the configuration and maturation of the microbiota. The immaturity of the infant microbiota is linked with the development of inflammatory, allergic, and dysmetabolic diseases. AIMS: To identify taxonomic changes associated with age and GDM and classify the maturity of the intestinal microbiota of children of mothers with GDM and children without GDM (n-GDM). METHODS: Next-generation sequencing was used to analyze the V3-V4 region of 16S rRNA gene. QIIME2 and Picrust2 were used to determine the difference in the relative abundance of bacterial genera between the study groups and to predict the functional profile of the intestinal microbiota. RESULTS: According to age, the older GDM groups showed a lower alpha diversity and different abundance of Enterobacteriaceae, Veillonella, Clostridiales, and Bacteroides. Regarding the functional profile, PWY-7377 and K05895 associated with Vitamin B12 metabolism were reduced in GDM groups. Compared to n-GDM group, GDM offspring had microbiota immaturity as age-discriminatory taxa in random forest failed to classify GDM offspring according to developmental age (OOB error 81%). Conclusion. Offspring from mothers with GDM have a distinctive taxonomic profile related to taxa associated with gut microbiota immaturity.


Assuntos
Bacteroides , Diabetes Gestacional , Microbioma Gastrointestinal , RNA Ribossômico 16S , Veillonella , Humanos , Diabetes Gestacional/microbiologia , Feminino , Gravidez , Bacteroides/genética , RNA Ribossômico 16S/genética , Veillonella/genética , Lactente , Adulto , Masculino , Disbiose/microbiologia , Fezes/microbiologia , Pré-Escolar , Sequenciamento de Nucleotídeos em Larga Escala
14.
J Clin Endocrinol Metab ; 109(6): 1526-1539, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38127956

RESUMO

CONTEXT: Pancreatic ß-cell function impairment is a key mechanism for developing gestational diabetes mellitus (GDM). Maternal and placental exosomes regulate maternal and placental responses during hyperglycemia. Studies have associated exosomal micro-RNAs (miRNAs) with GDM development. To date, no studies have been reported that evaluate the profile of miRNAs present in maternal and placental exosomes in the early stages of gestation from pregnancies that develop GDM. OBJECTIVE: We assessed whether early-pregnancy serum maternal and placenta-derived exosomes miRNA profiles vary according to pancreatic ß-cell function in women who will develop GDM. METHODS: A prospective nested case-control study was used to identify exosomal miRNAs that vary in early-pregnancy stages (<18 weeks of gestation) from women with normoglycemia and those who developed GDM based on their pancreatic ß-cell function using the homeostasis model assessment of pancreatic ß-cell function (HOMA-%ß) index. Early-pregnancy serum maternal and placenta-derived exosomes were isolated to obtain miRNA profiles. Potential target and pathway analyses were performed to identify molecular and metabolic pathways associated with the exosomal miRNAs identified. RESULTS: In early-pregnancy stages, serum maternal exosome size and concentration are modified in GDM group and fluctuate according to HOMA-%ß index. Serum maternal exosomal hsa-miR-149-3p and hsa-miR-455-3p in GDM are related to insulin secretion and signaling, lipolysis, and adipocytokine signaling. Early-pregnancy serum placenta-derived exosomes hsa-miR-3665 and hsa-miR-6727-5p in GDM are related to regulating genes involved in response to immunological tolerance of pregnancy and pathways associated with placental dysfunction. CONCLUSION: Early serum exosomal miRNAs differ depending on their origin (maternal or placental) and pancreatic ß-cell function. This research provides insights into the interactions between maternal and placental exosomal miRNAs and may have implications for identifying potential biomarkers or therapeutic targets for GDM.


Assuntos
Diabetes Gestacional , Exossomos , Células Secretoras de Insulina , MicroRNAs , Placenta , Humanos , Feminino , Gravidez , Diabetes Gestacional/sangue , Diabetes Gestacional/genética , Exossomos/metabolismo , Exossomos/genética , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiologia , Adulto , Placenta/metabolismo , MicroRNAs/sangue , Estudos de Casos e Controles , Estudos Prospectivos , Primeiro Trimestre da Gravidez/sangue
15.
Front Nutr ; 10: 1231873, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37637952

RESUMO

Introduction: Food Exchange Lists (FELs) are a user-friendly tool developed to help individuals aid healthy eating habits and follow a specific diet plan. Given the rapidly increasing number of new products or access to new foods, one of the biggest challenges for FELs is being outdated. Supervised machine learning algorithms could be a tool that facilitates this process and allows for updated FELs-the present study aimed to generate an algorithm to predict food classification and calculate the equivalent portion. Methods: Data mining techniques were used to generate the algorithm, which consists of processing and analyzing the information to find patterns, trends, or repetitive rules that explain the behavior of the data in a food database after performing this task. It was decided to approach the problem from a vector formulation (through 9 nutrient dimensions) that led to proposals for classifiers such as Spherical K-Means (SKM), and by developing this idea, it was possible to smooth the limits of the classifier with the help of a Multilayer Perceptron (MLP) which were compared with two other algorithms of machine learning, these being Random Forest and XGBoost. Results: The algorithm proposed in this study could classify and calculate the equivalent portion of a single or a list of foods. The algorithm allows the categorization of more than one thousand foods with a confidence level of 97% at the first three places. Also, the algorithm indicates which foods exceed the limits established in sodium, sugar, and/or fat content and show their equivalents. Discussion: Accurate and robust FELs could improve implementation and adherence to the recommended diet. Compared with manual categorization and calculation, machine learning approaches have several advantages. Machine learning reduces the time needed for manual food categorization and equivalent portion calculation of many food products. Since it is possible to access food composition databases of various populations, our algorithm could be adapted and applied in other databases, offering an even greater diversity of regional products and foods. In conclusion, machine learning is a promising method for automation in generating FELs. This study provides evidence of a large-scale, accurate real-time processing algorithm that can be useful for designing meal plans tailored to the foods consumed by the population. Our model allowed us not only to distinguish and classify foods within a group or subgroup but also to perform the calculation of an equivalent food. As a neural network, this model could be trained with other food bases and thus improve its predictive capacity. Although the performance of the SKM model was lower compared to other types of classifiers, our model allows selecting an equivalent food not from a group previously classified by machine learning but with a fully interpretable algorithm such as cosine similarity for comparing food.

16.
J Alzheimers Dis ; 94(2): 425-439, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37302035

RESUMO

BACKGROUND: Nutrition has relevant role in the pathogenesis of dementia. However, in Latin American Countries (LAC), it is unknown which type of diet the subjects with dementia and cognitive dysfunction have. OBJECTIVE: The main purpose of this study was to determine micro- and macronutrients and food frequency intake among the LAC population with mild cognitive impairment (MCI) and dementia. METHODS: A systematic review using PubMed, Cochrane, Lilacs, and Scielo databases. Energy intake as well as micro- and macronutrients intake were analyzed using a random-effect model and presented in a forest plot. RESULTS: Nine articles were included, an estimated energy intake of 1598.47 kcal (95% CI 1351.07-1845.88) was obtained. A daily consumption of 73.64 g/day (95% CI 64.07-83.2) of protein; 262.17 g/day (95% CI 214.51-309.93) of carbohydrates, and 57.91 g/day (95% CI 49.16-66.66) of fats were reported. A micronutrients daily intake consumption of 201.35µg/day of vitamin B9 (95% CI 125.32-277.38); 5.61µg/day of vitamin B12 (95% CI 2.53-8.70), and 139.67 mg/day of vitamin C (95% CI 59.33-220.02). Mineral intake of 637.32 mg/day of calcium (95% CI 288.54-986.11) and 9 mg/day of iron (95% CI 2.28-15.71) was obtained. A low intake of fruits and vegetables was found. CONCLUSION: Individuals with MCI and dementia from LAC have a nutritional deficiency characterized by a lower intake of fruits and vegetables, a high consumption of carbohydrates and protein, adequate fats intake and vitamins B12, vitamin C, and iron consumption, but a low intake of vitamin B9 and calcium.


Assuntos
Disfunção Cognitiva , Demência , Humanos , América Latina/epidemiologia , Cálcio , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/complicações , Vitaminas , Ácido Fólico , Ingestão de Energia , Vitamina B 12 , Ácido Ascórbico , Ingestão de Alimentos , Demência/epidemiologia , Demência/etiologia , Ferro
17.
Nutrients ; 15(22)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-38004098

RESUMO

Postmenopausal women are at an increased risk of developing metabolic syndrome (MetS) due to hormonal changes and lifestyle factors. Gut microbiota (GM) have been linked to the development of MetS, and they are influenced by dietary habits. However, the interactions between dietary patterns (DP) and the GM of postmenopausal women, as well as their influence on MetS, still need to be understood. The present study evaluated the DP and microbiota composition of postmenopausal Mexican women with MetS and those in a control group. Diet was assessed using a food frequency questionnaire, and the GM were profiled using 16S rRNA gene sequencing. Greater adherence to a "healthy" DP was significantly associated with lower values of MetS risk factors. GM diversity was diminished in women with MetS, and it was negatively influenced by an "unhealthy" DP. Moreover, a higher intake of fats and proteins, as well as lower amounts of carbohydrates, showed a reduction in some of the short-chain fatty acid-producing genera in women with MetS, as well as increases in some harmful bacteria. Furthermore, Roseburia abundance was positively associated with dietary fat and waist circumference, which may explain 7.5% of the relationship between this macronutrient and MetS risk factors. These findings suggest that GM and diet interactions are important in the development of MetS in postmenopausal Mexican women.


Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , Humanos , Feminino , Síndrome Metabólica/metabolismo , Pós-Menopausa , RNA Ribossômico 16S/genética , Dieta
18.
Diabetol Metab Syndr ; 15(1): 116, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37264408

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) represents the main metabolic alteration during pregnancy. The available methods for diagnosing GDM identify women when the disease is established, and pancreatic beta-cell insufficiency has occurred.The present study aimed to generate an early prediction model (under 18 weeks of gestation) to identify those women who will later be diagnosed with GDM. METHODS: A cohort of 75 pregnant women was followed during gestation, of which 62 underwent normal term pregnancy and 13 were diagnosed with GDM. Targeted metabolomics was used to select serum biomarkers with predictive power to identify women who will later be diagnosed with GDM. RESULTS: Candidate metabolites were selected to generate an early identification model employing a criterion used when performing Random Forest decision tree analysis. A model composed of two short-chain acylcarnitines was generated: isovalerylcarnitine (C5) and tiglylcarnitine (C5:1). An analysis by ROC curves was performed to determine the classification performance of the acylcarnitines identified in the study, obtaining an area under the curve (AUC) of 0.934 (0.873-0.995, 95% CI). The model correctly classified all cases with GDM, while it misclassified ten controls as in the GDM group. An analysis was also carried out to establish the concentrations of the acylcarnitines for the identification of the GDM group, obtaining concentrations of C5 in a range of 0.015-0.25 µmol/L and of C5:1 with a range of 0.015-0.19 µmol/L. CONCLUSION: Early pregnancy maternal metabolites can be used to screen and identify pregnant women who will later develop GDM. Regardless of their gestational body mass index, lipid metabolism is impaired even in the early stages of pregnancy in women who develop GDM.

19.
Nutrients ; 15(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37299553

RESUMO

Pecans (Carya illinoinensis) are considered a functional food due to the high content of polyunsaturated fatty acids, dietary fiber and polyphenols. To determine the effect of whole pecans (WP) or a pecan polyphenol (PP) extract on the development of metabolic abnormalities in mice fed a high-fat (HF) diet, we fed C57BL/6 mice with a Control diet (7% fat), HF diet (23% fat), HF containing 30% WP or an HF diet supplemented with 3.6 or 6 mg/g of PP for 18 weeks. Supplementation of an HF diet with WP or PP reduced fat mass, serum cholesterol, insulin and HOMA-IR by 44, 40, 74 and 91%, respectively, compared to the HF diet. They also enhanced glucose tolerance by 37%, prevented pancreatic islet hypertrophy, and increased oxygen consumption by 27% compared to the HF diet. These beneficial effects were associated with increased thermogenic activity in brown adipose tissue, mitochondrial activity and AMPK activation in skeletal muscle, reduced hypertrophy and macrophage infiltration of subcutaneous and visceral adipocytes, reduced hepatic lipid content and enhanced metabolic signaling. Moreover, the microbial diversity of mice fed WP or PP was higher than those fed HF, and associated with lower circulating lipopolysaccharides (~83-95%). Additionally, a 4-week intervention study with the HF 6PP diet reduced the metabolic abnormalities of obese mice. The present study demonstrates that WP or a PP extract prevented obesity, liver steatosis and diabetes by reducing dysbiosis, inflammation, and increasing mitochondrial content and energy expenditure. Pecan polyphenols were mainly condensed tannin and ellagic acid derivatives including ellagitannins as determined by LC-MS. Herein we also propose a model for the progression of the HF diet-mediated metabolic disorder based on early and late events, and the possible molecular targets of WP and PP extract in preventive and intervention strategies. The body surface area normalization equation gave a conversion equivalent to a daily human intake dose of 2101-3502 mg phenolics that can be obtained from 110-183 g pecan kernels/day (22-38 whole pecans) or 21.6-36 g defatted pecan flour/day for an average person of 60 kg. This work lays the groundwork for future clinical studies.


Assuntos
Carya , Diabetes Mellitus , Fígado Gorduroso , Camundongos , Humanos , Animais , Dieta Hiperlipídica/efeitos adversos , Polifenóis/farmacologia , Polifenóis/metabolismo , Disbiose/prevenção & controle , Disbiose/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/prevenção & controle , Fígado Gorduroso/prevenção & controle , Fígado/metabolismo , Inflamação/prevenção & controle , Inflamação/metabolismo , Diabetes Mellitus/metabolismo , Hipertrofia , Metabolismo Energético
20.
Biomedicines ; 11(2)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36831031

RESUMO

BACKGROUND: M1 macrophages involved in pro-inflammatory processes can be induced by low-density lipoproteins (LDL), giving rise to foam cells. In the atheroma plaque, it has been identified that males present more advanced lesions associated with infiltration. Therefore, our study aims to investigate sex-related changes in the transcriptome of M1 macrophages during the internalization process of LDL particles. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy male and female subjects were separated using Hystopaque, and monocytes were isolated from PBMCs using a positive selection of CD14+ cells. Cells were stimulated with LDL 10 µg/mL, and the transcriptional profile of M1 macrophages performed during LDL internalization was determined using a Clariom D platform array. RESULTS: Chromosome Y influences the immune system and inflammatory responses in males expressing 43% of transcripts in response to LDL treatment. Males and females share 15 transcripts, where most correspond to non-coding elements involved in oxidative stress and endothelial damage. CONCLUSIONS: During LDL internalization, male monocyte-derived M1 macrophages display more marked proinflammatory gene expression. In contrast, female M1 macrophages display a more significant number of markers associated with cell damage.

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