RESUMO
Skeletal muscle (SkM) is a plastic and dynamic tissue, essential in energy metabolism. Growing evidence suggests a close relationship between intramuscular fat accumulation, oxidative stress (OS), extracellular matrix (ECM) remodeling, and metabolic deregulation in SkM. Nowadays natural products emerge as promising alternatives for the treatment of metabolic disorders. We have previously shown that chia seed administration reverts SkM lipotoxicity and whole-body insulin resistant (IR) in sucrose-rich diet (SRD) fed rats. The purpose of the present study was to assess the involvement of OS and fibrosis in SkM metabolic impairment of insulin-resistant rats fed a long-term SRD and the effects of chia seed upon these mechanisms as therapeutic strategy. Results showed that insulin-resistant SRD-fed rats exhibited sarcopenia, increase in lipid peroxidation, altered redox state, and ECM remodeling-increased collagen deposition and lower activity of the metalloproteinase 2 (MMP-2) in SkM. Chia seed increased ferric ion reducing antioxidant power and glutathione reduced form levels, and the activities of glutathione peroxidase and glutathione reductase enzymes. Moreover, chia seed reversed fibrosis and restored the MMP-2 activity. This work reveals a participation of the OS and ECM remodeling in the metabolic alterations of SkM in our experimental model. Moreover, current data show novel properties of chia seed with the potential to attenuate SkM OS and fibrosis, hallmark of insulin-resistant muscle.
RESUMO
To evaluate the effect of high-intensity interval training (HIT) on the cardiorespiratory performance and substrate oxidation pattern in insulin-resistant and insulin-sensitive obese adolescents. METHODS: We recruited 25 obese adolescents in three schools, and trained them in six HIT sessions, comprising of six series at 100% and recovery at 50% peak velocity (Vpeak). For the evaluation, the participants were divided into two groups: insulin-resistant (IR, n = 12; HOMA index ≥3.16) and insulin-sensitive (IS, n = 13). All participants underwent cardiopulmonary and indirect calorimetry testing. We compared the effects of HIT before and after the intervention among the two groups. The data were analyzed using Student's t and Mann-Whitney (intergroup comparisons) and Student's t and Wilcoxon (pre- and post-training comparisons) tests; and Cohen's d (influence of HIT). RESULTS: There was a significant post-training increase in Vpeak, oxygen consumption (VO2), velocity (V), and heart rate (HR) at the exertion intensity at the first ventilatory anaerobic threshold (VAT1) in both groups (p < 0.05; d < 0.02). The exercise promoted changes in substrate oxidation rates of the groups, with an increase in carbohydrate oxidation (CHOox) for both IR (p = 0.064) and IS (p = 0.034). CONCLUSION: Six HIT sessions improved cardiorespiratory performance in both groups and increased CHOox in insulin-sensitive obese adolescents, suggesting its utility for increasing physical fitness and controlling glycemia in these population groups.
Assuntos
Aptidão Cardiorrespiratória , Treinamento Intervalado de Alta Intensidade , Obesidade Infantil , Adolescente , Aptidão Cardiorrespiratória/fisiologia , Humanos , Insulina , Consumo de Oxigênio , Aptidão FísicaRESUMO
Given obesity and its associated metabolic disorders have reached epidemic proportions, the study of therapeutic strategies targeting white adipose tissue (WAT) are of main research interest. We previously shown that α-linolenic acid-rich chia seed was able to ameliorate a wide range of metabolic disorders including body fat accretion in sucrose-rich diet (SRD)-fed rats, an experimental model of visceral adiposity and insulin resistance. However, the mechanisms involved are not fully clarified. The aim of this study was to evaluate the effect of chia seed administration upon WAT remodeling and key enzymes that controls lipolysis, insulin signaling (tAKT, pAKT), and GLUT-4 levels in different visceral fat pad depots (epididymal -eWAT- and retroperitoneal -rWAT- adipose tissues) of SRD-fed rats. Results showed that chia seed reduces adipocytes hypertrophy, the increased lipid content and collagen deposition in both WAT. These changes were accompanied by a significant reduction of HSL and ATGL protein levels in eWAT and HSL protein levels in rWAT. Moreover, chia seed restored the altered expression pattern of the pAKT observed in SRD-fed rats, and modulated GLUT-4 levels. Chia seed could be a dietary intervention of great relevance with potential beneficial effects in the management of body fat excess and WAT function.
Assuntos
Salvia , Ácido alfa-Linolênico , Adiposidade , Animais , Colágeno , Dieta , Insulina/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Extratos Vegetais , Ratos , Ratos Wistar , Roedores/metabolismo , Salvia/metabolismo , Salvia hispanica , Ácido alfa-Linolênico/farmacologiaRESUMO
SHORT syndrome is a rare developmental disorder frequently associated with growth failure and insulin resistant diabetes mellitus (IRDM). Since GH has a diabetogenic effect, GH therapy has been regarded as a contraindication. We observed a Brazilian girl with SHORT syndrome who received GH therapy from 4 6/12 years of age for SGA short stature. GH dosage was increased from 0.23 to 0.36 mg/kg/week, but statural response to GH therapy remained poor. Her blood HbA1c level, though it remained 5.5-6.0% in childhood, began to elevate with puberty and increased to 9.2% at 10 6/12 years of age, despite the discontinuation of GH therapy at 9 11/12 years of age. Laboratory studies indicated antibody-negative IRDM. She was treated with metformin and canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia and mild nocturnal hypoglycemia and reduced her blood HbA1c around 7%. Whole exome sequencing revealed a de novo heterozygous pathogenic variant (c.1945C>T:p.(Arg649Trp)) in PIK3R1 known as the sole causative gene for SHORT syndrome. Subsequent literature review for patients with molecularly confirmed SHORT syndrome revealed the development of IRDM in 10 of 15 GH-untreated patients aged ≥12 years but in none of three GH-treated and six GH-untreated patients aged ≤10 years. These findings imply a critical role of pubertal development and/or advanced age rather than GH therapy in the development of IRDM, and a usefulness of SGLT2 inhibitor in the treatment of IRDM.
Assuntos
Diabetes Mellitus/diagnóstico , Transtornos do Crescimento/complicações , Hipercalcemia/complicações , Resistência à Insulina/fisiologia , Doenças Metabólicas/complicações , Nefrocalcinose/complicações , Brasil , Canagliflozina/administração & dosagem , Criança , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Quimioterapia Combinada , Feminino , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/metabolismo , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/tratamento farmacológico , Hipercalcemia/metabolismo , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Metformina/administração & dosagem , Nefrocalcinose/diagnóstico , Nefrocalcinose/tratamento farmacológico , Nefrocalcinose/metabolismo , Puberdade/efeitos dos fármacos , Puberdade/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagemRESUMO
Las vitaminas (Vit.) C, E y A, junto al zinc (Zn++) y cobre (Cu++) colaboran en la prevención de las comorbilidades asociadas a la obesidad. El objetivo del trabajo fue evaluar las concentraciones séricas (Cs) de Vit. C, E y A, así como las del Zn++ y Cu++ en púberes con exceso de peso (EP) y resistencia a la insulina (RI). El estudio fue descriptivo, correlacional, de campo y transversal. Las variables se compararon entre los púberes normopeso (NP)/sin RI y quienes tenían EP (con y sin RI). Se emplearon las pruebas de Pearson y Spearman, test de Student, U de Mann-Whitney, Kruskal-Wallis y el estadístico Z. Los adolescentes con EP/RI presentaron Cs de Zn++ menores que aquellos con EP/sin RI, y que el grupo control (p=0,010), siendo probablemente la RI lo que define esta disminución ya que el Zn++ fue similar entre los púberes con y sin EP. El 12,0% de los sujetos con EP/RI presentaron la relación Vit. E/Colesterol Total (CT)< 2,25 mmol/mol, comparados con el 4,8% y 8,0% observado en los adolescentes con EP/sin RI y los controles, respectivamente (p=0,012). Los adolescentes con EP/ RI evidenciaron una menor protección antioxidante y Cs de Zn++ inferiores al resto de los grupos evaluados.
Vitamins (Vit.) C, E and A, together with zinc (Zn++) and copper (Cu++) play an important role in the prevention of comorbidities associated with obesity. The objective of this work was to evaluate serum concentrations (Sc) of Vit. C, E and A, and those of Zn++ and Cu++ in a pubertal overweight (OW) and insulin-resistant (IR) population. The study was descriptive, correlational and cross-sectional. Variables were compared between the normalweight pubescent population, non-IR and those OW (IR or non-IR). Correlations between variables were assessed using Pearson and Spearman tests, the Student t test, Mann-Whitney U test, Kruskal-Wallis test and the statistical Z. OW and IR adolescents presented lower Zn++ than those OW non-IR, and the control group (p=0.010). Probably it is being IR what defines this decrease since the Zn++ was similar in the pubertal population with and without OW. In the OW and RI group of adolescents, there was a frequency of alterations in vit. E/CT (<2.25 mmol/mol) of 12.0%, compared to 4.8% and 8.0% in OW and non-IR and control adolescents, respectively (p=0.012) OW and IR adolescents showed a lower antioxidant protection and lower Zn++ than other groups evaluated.
As vitaminas (Vit.) C, E e A, em conjunto com zinco (Zn++) e Cobre (Cu++) desempenham um papel importante na prevenção de comorbidades associadas à obesidade. O objetivo do trabalho foi avaliar as concentrações séricas (Cs) de Vit. C, E e A, bem como as de Zn++ e de Cu++ em púberes com excesso de peso (EP) e resistência à insulina (RI). O estudo foi descritivo, correlacional, de campo e transversal. As variáveis foram comparadas entre os púberes normopeso (NP)/sem RI e aqueles que tinham EP (com e sem RI). Foram utilizados os testes de Pearson e Spearman, teste de Student, U de Mann- Whitney, Kruskal-Wallis e o estatístico Z. Adolescentes com EP/RI apresentaram Cs de Zn++ menores do que aqueles com EP/sem RI, e que o grupo controle (p=0,010), sendo provavelmente a RI o que define esta diminuição, visto que o Zn++ foi similar entre os púberes com e sem EP. 12,0% de sujeitos com EP/RI apresentaram a relação Vit. E/Colesterol Total (CT) <2,25 mmol/mol, comparados com 4,8% e 8,0% observado nos adolescentes com EP/sem RI e os controles, respectivamente (p=0,012). Adolescentes com EP e RI mostraram menor proteção antioxidante e Cs de Zn++ inferiores ao resto dos grupos avaliados.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Resistência à Insulina , Proteínas Sanguíneas/análise , Obesidade , Ácido Ascórbico , Vitamina A , Vitamina E , ZincoRESUMO
Las enfermedades cardiovasculares y el síndrome metabólico son patologías que afectan a gran parte de la población mundial, de etiología poligénica y multifactorial, resultado de la interacción entre factores genéticos, ambientales, sociales y culturales. Los principales genes candidatos a estudiar son aquellos relacionados con la regulación de la homeostasis de la glucosa, del metabolismo lipídico y/o de la secreción y acción de la insulina, como son el gen de los Receptores de los Proliferadores Perixosomales Activados gamma 2 (PPARγ2), la Proteína Enlazante de Ácidos Grasos Intestinal (FABP2) y la Apolipoproteína E (ApoE). Evaluar la relación entre los polimorfismos Pro12Ala del gen PPARγ2, Ala54Thr del gen FABP2 y del gen de ApoE en habitantes del Sector Los Eucaliptos de la Parroquia San Juan. 308 individuos de dicha comunidad, 98 hombres y 210 mujeres, clasificados en hipercolesterolémicos, hipertrigliceridémicos, resistentes a la insulina y controles de acuerdo a sus niveles de colesterol total, triglicéridos e índice HOMA. Extracción de 10 mL de sangre venosa para la determinación de química sanguínea y extracción de ADN, amplificación mediante PCR de un fragmento de 102pb del gen de PPARγ2, uno de 180pb del gen de FABP2 y otro de 244pb del gen de ApoE, y posterior RFLP. Se encontró una frecuencia alélica de 0,91 para el alelo Pro y 0,09 para el Ala del gen de PPARγ2; 0,70 para el alelo Ala del gen FABP2 y 0,30 para el Thr, mientras que para los alelos del gen de ApoE la frecuencia fue de ε2=0,05, ε3=0,80 y ε4=0,15. Se encontró relación entre el alelo ε4 de ApoE y la hipercolesterolemia, además del alelo ε2 como factor protector ante el desarrollo de hipercolesterolemia, hipertrigliceridemia y resistencia a la insulina, no encontrándose asociación alguna entre los polimorfismos de los restantes genes y las patologías mencionadas.
Cardiovascular disease and metabolic syndrome are diseases that affect worldwide, with multiple genetic and environmental components contributing to susceptibility. The main candidate genes to study are those related to the regulation of glucose homeostasis, lipid metabolism, insulin secretion and action and obesity, these include the genes for Peroxisome proliferator-activated receptor gamma 2 (PPARγ2), fatty acid-binding protein 2 (FABP2) and Apolipoprotein E (Apo E). The aim of this study was to investigate the relationship between polymorphisms of Pro12Ala PPARγ2 gene, Ala54Thr FABP2 gene and the ApoE gene in residents from the The Eucaliptus of the Parroquia San Juan. 308 subjects, 98 men and 210 women, classified as hypercholesterolemic, hypertriglyceridemic, insulin resistant and controls according to their levels of total cholesterol, triglycerides and HOMA index. Extraction of 10 mL whole blood for determination of chemistry and DNA extraction, PCR amplification of a 102 bp fragment PPARγ2 gene, a 180 bp FABP2 gene and a 244 bp of ApoE gene, and subsequent RFLP. An allele frequency for allele Pro 0.91 and 0.09 for gene PPARγ2 Ala and 0.70 for the allele of the gene FABP2 Ala and 0.30 for Thr, while for the different alleles of ApoE gene frequency was ε2=0.05, ε3=0.80 and ε4=0.15. We found a relationship between the ApoE ε4 allele and hypercholesterolemia, in the other hand, Apo E ε2 allele was found as a protective factor against the development of hypercholesterolemia, hypertriglyceridemia and insulin resistance, we did not found association between polymorphisms of the other genes and the pathologies mentioned above.
Assuntos
Humanos , Masculino , Adulto , Feminino , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Insulina/análise , Insulina/genética , Insulina/química , Polimorfismo Genético , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Análise Química do Sangue , Transtornos do Metabolismo de Glucose , Hematologia , Transtornos do Metabolismo dos LipídeosRESUMO
Determinar el efecto de la terapia con metformina en pacientes infértiles con síndrome de ovarios poliquísticos. Estudio clínico, prospectivo y descriptivo. Incluyó pacientes con diagnóstico de síndrome de ovarios poliquísticos, infertilidad y resistencia a la insulina, a las que se les administró tratamiento con metformina por 3 meses. Las pacientes que no se embarazaron en ese período recibieron tratamiento con citrato de clomifeno, hasta un máximo de 6 meses. En el Servicio de Fertilidad Maternidad "Concepción Palacios". Caracas. Resultados: Se completó un total de 62 pacientes. La tasa de embarazo de 25,8 por ciento (19 pacientes). Un 57,9 por ciento de las pacientes lograron embarazo con 3 meses de tratamiento, con una P= 0,492 lo cual no fue estadísticamente significante. La tasa de embarazos con citrato de clomifeno fue de 23,5 por ciento (8 pacientes), P=0,684. El 63,2 por ciento (12) tuvo un embarazo a término. La tasa de aborto fue de 26,3 por ciento (5). La metformina induce ovulación espontánea en pacientes con síndrome de ovarios poliquísticos. No existe diferencia estadística entre la tasa de embarazos con la terapia con metformina sola y metformina con citrato de clomifeno. La metformina mejora la evolución de embarazo
To determine the effect of treatment with metformin in infertile patients with polycystic ovary syndrome. Clinical, prospective and descriptive study. Infertile anovulatory patients with polycystic ovary syndrome and insulin resistant were included, and all of them, were treated with metformin for 3 months. Patients who did not ovulate in this time, received clomiphene citrate for 6 months. Fertility Service of Maternidad "Concepcion Palacios". 62 infertile patients were included in this study. The pregnancy rate was 25.8 percent (19 patients). The 57.9 percent of women became pregnant with metformin administration for 3 months, with P= 0.492, it was not statistical significance. The pregnancy rate with clomiphene citrate was 23.5 percent (8 patients), P= 0.684. The abortion rate was 26.3 percent (5). The metformin induce ovulation in anovulatory polycystic ovary syndrome women, whereas the pregnancy rate resulted similar in both treatment groups: metformin alone and metformin and clomiphene citrate