RESUMEN

Noncoding microRNAs are involved in lipid and carbohydrate metabolism pathways and are powerful regulators of gene expression. The goals of this study were to evaluate the temporal expression profiles of miRNAs in rat adipose tissue and predict mRNA−microRNA interactions. Newly weaned Wistar rats were divided into groups fed a standard diet and high-sucrose diet (HSD). The HSD contains 66.86% carbohydrates (40.45% standard diet, 40.45% condensed milk, and 8.58% crystal sugar), and the HSD was provided for 4, 8 and 15-week periods to investigate the expression levels of miRNAs in visceral adipose tissue using RT−qPCR. Target selection, enriched pathways and networks were analyzed in silico. The factor consumption time significantly was associated to decreases (p < 0.05) in the expression levels of the following miRNAs: 124-5p, 125-5p, 126-5p, 200c-3p, and 212-3p in all experimental groups. The factor diet significantly influenced rno-miR-124-5p, 200c-3p, and 212-3p expression (p < 0.05). A significant reduction (p < 0.05) in rno-miR-27a-3p expression was observed. The biological processes involved key pathways regulating fat deposition. Our findings provide important insights into downregulated miRNA expression patterns in visceral adipose tissue, adiposity level, hyperinsulinemia and increased VLDL-c and triglyceride levels.

Asunto(s)

Sacarosa en la Dieta , Grasa Intraabdominal , MicroARNs , Animales , Sacarosa en la Dieta/efectos adversos , Grasa Intraabdominal/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Ratas Wistar

RESUMEN

BACKGROUND: Metabolic imprinting describes associations between nutritional experiences of early life and the development of diseases later in life. The goal of this study was to evaluate the metabolic imprinting induced by a high-sugar diet (HSD) and its effects on microRNA (miRNA) expression and insulin resistance (IR) in young rats. We assessed the effects of expression of adipogenic (miR-200c) and metabolic (miR-126a) miRNAs in retroperitoneal white adipose tissue (rWAT) on IR development. METHODS AND RESULTS: Weaned male Wistar rats (N = 6) were fed a standard chow diet or HSD (68% carbohydrates) for 4-, 8-, or 12-weeks. Serum samples were collected to measure triacylglycerol and VLDL-cholesterol, and we assessed glucometabolic parameters (glucose, insulin, HOMA-IR, and QUICKI). rWAT was collected for microRNA analysis (N = 3). The HSD resulted in body fat accretion and IR after 8-weeks, which resolved by 12-weeks. Moreover, the HSD had a time-dependent effect on miRNA relative expression, downregulating rno-miR-200c-3p at week 8 and rno-miR-126a-3p at week 12. CONCLUSIONS: MiR-200 family dysregulation has been related to IR, and miR-126a downregulation could be associated with the improvement in IR observed after a 12-week HSD feeding period. This is the first time that excessive sugar intake post-weaning has been associated with miRNA production by rWAT with an impact on IR development.

Asunto(s)

Resistencia a la Insulina , MicroARNs , Animales , Dieta , Glucosa/metabolismo , Resistencia a la Insulina/genética , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Ratas Wistar

RESUMEN

Objective Provide a comprehensive view of the events surrounding the sugar consumption, under conditions of energy equivalence; through the analysis of behavioral aspects of intake, and of biochemical, metabolic and physiological parameters, as well as the effect of this nutrient on the plasticity of adipose tissue. Materials and methods Newly weaned male Wistar rats were classified in two groups and subjected to the following normocaloric diets: standard chow diet or to high-sugar diet (HSD) ad libitum for 18 weeks. Results The animals submitted to the HSD were associated with a lower caloric intake during the 18 weeks of experimentation. However, the HSD induced a significant increase in body weight, white adipose tissue weight, adiposity index, Lee index, and the levels of triglycerides and very low-density lipoprotein in the serum. In addition, it induced glucose intolerance, insulin resistance and compensatory increase of insulin secretion by pancreatic ß-cells. Also increased heart rate and induced hyperplasia, and hypertrophy of retroperitoneal visceral adipose tissue. In the liver, the HSD was associated with increased hepatic lipid content (i.e., triglycerides and cholesterol) and hepatomegaly. Conclusion The post-weaning consumption of HSD induces an adaptive response in metabolism; however, such an event is not enough to reverse the homeostatic imbalance triggered by the chronic consumption of this macronutrient, leading to the development of metabolic syndrome, irrespective of caloric intake. These findings corroborate recent evidence indicating that sugar is a direct contributor to metabolic diseases independent of a positive energy balance. Arch Endocrinol Metab. 2020;64(1):71-81.

Asunto(s)

Tejido Adiposo/metabolismo , Azúcares de la Dieta/metabolismo , Ingestión de Energía , Metabolismo Energético , Enfermedades Metabólicas/metabolismo , Obesidad/metabolismo , Animales , Azúcares de la Dieta/efectos adversos , Azúcares de la Dieta/sangre , Masculino , Enfermedades Metabólicas/sangre , Obesidad/sangre , Obesidad/etiología , Ratas , Ratas Wistar

RESUMEN

ABSTRACT Objective Provide a comprehensive view of the events surrounding the sugar consumption, under conditions of energy equivalence; through the analysis of behavioral aspects of intake, and of biochemical, metabolic and physiological parameters, as well as the effect of this nutrient on the plasticity of adipose tissue. Materials and methods Newly weaned male Wistar rats were classified in two groups and subjected to the following normocaloric diets: standard chow diet or to high-sugar diet (HSD) ad libitum for 18 weeks. Results The animals submitted to the HSD were associated with a lower caloric intake during the 18 weeks of experimentation. However, the HSD induced a significant increase in body weight, white adipose tissue weight, adiposity index, Lee index, and the levels of triglycerides and very low-density lipoprotein in the serum. In addition, it induced glucose intolerance, insulin resistance and compensatory increase of insulin secretion by pancreatic β-cells. Also increased heart rate and induced hyperplasia, and hypertrophy of retroperitoneal visceral adipose tissue. In the liver, the HSD was associated with increased hepatic lipid content (i.e., triglycerides and cholesterol) and hepatomegaly. Conclusion The post-weaning consumption of HSD induces an adaptive response in metabolism; however, such an event is not enough to reverse the homeostatic imbalance triggered by the chronic consumption of this macronutrient, leading to the development of metabolic syndrome, irrespective of caloric intake. These findings corroborate recent evidence indicating that sugar is a direct contributor to metabolic diseases independent of a positive energy balance. Arch Endocrinol Metab. 2020;64(1):71-81

Asunto(s)

Animales , Masculino , Ratas , Ingestión de Energía , Tejido Adiposo/metabolismo , Metabolismo Energético , Azúcares de la Dieta/metabolismo , Enfermedades Metabólicas/metabolismo , Obesidad/metabolismo , Ratas Wistar , Azúcares de la Dieta/efectos adversos , Azúcares de la Dieta/sangre , Enfermedades Metabólicas/sangre

RESUMEN

Endurance exercise is a remarkable intervention for the treatment of many diseases. Mitochondrial changes on skeletal muscle are likely important for many of the benefits provided by exercise. In this study, we aimed to evaluate the effects that a regular physical activity (swimming without workload) has on mitochondrial morphological alterations and glucometabolic parameters induced by a high-sugar diet (HSD). Weaned male Wistar rats fed with a standard diet or a HSD (68% carbohydrate) were subjected to 60 minutes of regular physical activity by swimming (without workload) for four- (20 sessions) or eight-week (40 sessions) periods. After training, animals were euthanized and the sera, adipose tissues, and skeletal muscles were collected for further analysis. The HSD increased body weight after an 8-week period; it also increased the fat pads and the adipose index, resulting in glucose intolerance and insulin resistance (IR). Transmission electron microscopy showed an increase in alterations of mitochondrial ultrastructure in the gastrocnemius muscle, as well as a decrease in superoxide dismutase (SOD) activity, and an increase in protein carbonylation. Regular physical activity partially reverted these alterations in rats fed a HSD, preventing mitochondrial morphological alterations and IR. Moreover, we observed a decrease in Pgc1α expression (qPCR analysis) in STD-EXE group and a less pronounced reduction in HSD-EXE group after an 8-week period. Thus, regular physical activity (swimming without workload) in rats fed a HSD can prevent mitochondrial dysfunction and IR, highlighting the crucial role for physical activity on metabolic homeostasis.

Asunto(s)

Dieta de Carga de Carbohidratos , Glucosa/metabolismo , Mitocondrias/ultraestructura , Tejido Adiposo/metabolismo , Animales , Glucemia/análisis , Citrato (si)-Sintasa/metabolismo , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Resistencia a la Insulina , Masculino , Microscopía Electrónica de Transmisión , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , Estrés Oxidativo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Condicionamiento Físico Animal , Carbonilación Proteica , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Natación

RESUMEN

SCOPE: We have previously shown an increase in adipocyte size and lipid content in retroperitoneal white adipose tissue (rWAT) induced by an 8-week high-sugar diet (HSD). In this study, we assessed the effect of a HSD on the transcriptional activity of adipogenic genes in a time-course study to provide insight regarding the genetic networks involved in the rWAT response to dietary sugar. METHODS AND RESULTS: Weaned male Wistar rats were fed a standard chow diet or HSD (68% carbohydrates) for 4, 8 or 12 weeks, and rWAT was removed for histopathology and PCR array (adipogenesis) analyses. The HSD induced adipocyte hypertrophy and hyperplasia in rWAT after 12 weeks of ingestion. Additionally, the HSD altered serum VLDL-cholesterol, triacylglycerol and glucometabolic parameters. Hierarchical clustering revealed HSD-induced changes in the expression patterns of the tested gene set. Pathway analysis, which used the enrichment analysis algorithm of the Thompson Reuters MetaCore platform, associated a cluster of differentially expressed genes with canonical pathways related to regulating adipocyte differentiation and proliferation (p-value < 10(-7)). CONCLUSION: HSD feeding post-weaning increased both the adipocyte size and number by simultaneously up-regulating pro-adipogenic signals (the PPARγ pathway) and down-regulating anti-adipogenic signals (Wnt pathway) in young adults.

Asunto(s)

Adipocitos/efectos de los fármacos , Sacarosa en la Dieta/administración & dosificación , Grasa Intraabdominal/patología , Adipogénesis/efectos de los fármacos , Animales , Composición Corporal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Aumento de la Célula , Proliferación Celular/efectos de los fármacos , VLDL-Colesterol/sangre , Sacarosa en la Dieta/efectos adversos , Regulación hacia Abajo , Hiperplasia/metabolismo , Hipertrofia/metabolismo , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Masculino , PPAR gamma/genética , PPAR gamma/metabolismo , Ratas , Ratas Wistar , Triglicéridos/sangre , Regulación hacia Arriba , Vía de Señalización Wnt

RESUMEN

The presence of leptin receptors in white adipose tissue (WAT) suggests a type of peripheral control during the development of obesity and other metabolic disorders. Both diet composition and exercise influence serum leptin; however, the effect of their combination on long-term WAT leptin metabolism is unknown. In this study, rats fed with standard or high-sugar diets (HSD) were simultaneously subjected to running training for 4- and 8-week periods, and the retroperitoneal WAT (rWAT) was evaluated for adipocyte cell size, lipid and catecholamine content, Lep, OB-Rb and Ucp2 mRNA transcription levels, and circulating leptin and non-esterified fatty acids (NEFA). The HSD groups displayed a higher adiposity index and rWAT weight, Lep mRNA and protein upregulation, and a period-dependent effect on OB-Rb mRNA expression. Exercise decreased serum leptin and upregulated the OB-Rb mRNA levels. However, in rats fed with an HSD, the increase in OB-Rb mRNA and reduction in catecholamine levels resulted in a high level of adiposity and hyperleptinemia. The combination of training and an HSD decreases the NEFA levels and upregulating the Ucp2 mRNA expression in the 4-week period, while downregulating the Ucp2 mRNA expression in the 8-week period without changing the NEFA levels. Our results suggest that an HSD induces an increase in leptin expression in rWAT, while reducing adipocytes via leptin-mediated lipolysis after an 8-week period. In exercised rats fed an HSD, TAG synthesis and storage overlaps with lipolysis, promoting fat store development and Lep mRNA and plasma protein upregulation in adult rats.

Asunto(s)

Carbohidratos de la Dieta/farmacología , Grasa Intraabdominal/efectos de los fármacos , Leptina/genética , Condicionamiento Físico Animal , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Catecolaminas/metabolismo , Tamaño de la Célula/efectos de los fármacos , Carbohidratos de la Dieta/administración & dosificación , Ácidos Grasos no Esterificados/sangre , Ácidos Grasos no Esterificados/metabolismo , Expresión Génica/efectos de los fármacos , Grasa Intraabdominal/citología , Grasa Intraabdominal/metabolismo , Canales Iónicos/genética , Canales Iónicos/metabolismo , Leptina/sangre , Leptina/metabolismo , Lípidos/análisis , Lipólisis/efectos de los fármacos , Masculino , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Radioinmunoensayo , Ratas , Ratas Wistar , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Proteína Desacopladora 2

RESUMEN

The mitochondrial uncoupling proteins (UCPs) of interscapular brown adipose tissue (iBAT) and of muscles play important roles in energy balance. For instance, the expression of UCP1 and UCP3 are modulated by free fatty acid gradients induced by high-sugar diets and acute exercise that is dependent on sympathetic stimulation. However, the effects of endurance training in animals fed with high-sugar diets are unknown. This study aims to evaluate the long-term effects of diet and exercise on UCP1 and UCP3 levels and energy balance efficiency. Rats fed with standard or high-sugar (HSD) diets were simultaneously subjected to running training over an 8-week period. After the training period, the rats were decapitated, and the iBAT and gastrocnemius muscle tissues were removed for evaluation of the ß3-receptor, Ucp1, and Ucp3 mRNA and protein expression, which were analyzed by quantitative reverse transcriptase polymerase chain reaction and Western blot, respectively. Groups fed with an HSD displayed a higher adiposity index and iBAT weight (P < .05), whereas exhibited an up-regulation of Ucp1 mRNA and protein levels (P < .05). Training increased ß3-receptor mRNA in iBAT and reduced the Ucp3 mRNA in muscle tissues. In association with an HSD, training restored the increasing ß3-receptor mRNA and greatly up-regulated the levels of Ucp3 mRNA. Therefore, training blocked the HSD-induced up-regulation of UCP1 expression in iBAT, whereas it up-regulated the expression of Ucp3 mRNA in muscle. These results suggest that training enhances the relationship between Ucp1/Ucp3 mRNA levels, which could result in higher energy efficiency, but not when HSD-induced elevated sympathetic activity is maintained.

Asunto(s)

Tejido Adiposo Pardo/metabolismo , Dieta , Sacarosa en la Dieta/administración & dosificación , Canales Iónicos/metabolismo , Proteínas Mitocondriales/metabolismo , Resistencia Física , Animales , Western Blotting , Peso Corporal , Citrato (si)-Sintasa/metabolismo , Ingestión de Energía , Metabolismo Energético , Canales Iónicos/genética , Masculino , Proteínas Mitocondriales/genética , Músculo Esquelético/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Proteína Desacopladora 2 , Proteína Desacopladora 3 , Regulación hacia Arriba