RESUMEN
Aerobic training induces adaptive responses in skeletal muscles and white adipose tissues, thus facilitating lipid utilization as energy substrates during a physical exercise session. However, the effects of training on cytokines levels and on transcription factors involved in lipid metabolism in muscle and different white adipose depots are still unclear; therefore, these were the aims of the present study. Nineteen adult male Wistar rats were randomly assigned to a trained group or a control, non-trained group. The 10-week training protocol consisted of running on a treadmill, during 1 hour per day, 5 days per week, at 75% of maximum aerobic speed. As expected, trained rats improved their aerobic performance and had augmented citrate synthase activity in the soleus, while the control rats did not. Although body weight was not different between groups, the adiposity index and white adipose depots (ie, epididymal and retroperitoneal) were reduced in trained rats. Training reduced serum concentration of insulin, but failed to change serum concentrations of glucose, triacylglycerol, total cholesterol, and nonesterified fatty acids. Training increased sterol regulatory element-binding protein-1c expression in the gastrocnemius and epididymal adipose tissue, and reduced peroxisome proliferator-activated receptor γ (PPARγ) expression in most of the tissues analyzed. The expression of PPARα and carnitine palmitoyltransferase 1 increased in the gastrocnemius and mesenteric adipose tissue but reduced in epididymal adipose tissue. Triacylglycerol content and tribbles 3 expression reduced in the gastrocnemius of trained rats. Tumor necrosis factor-α and interleukin-6 were increased in all adipose depots evaluated. Collectively, our data indicate that the 10-week aerobic training changed gene expression to improve muscle oxidative metabolism and facilitate lipid degradation in adipose tissues. Our data also highlight the existence of adaptive responses that are distinct between the skeletal muscle and white adipose tissue and between different adipose depots.
Asunto(s)
Tejido Adiposo Blanco/metabolismo , Regulación de la Expresión Génica/fisiología , Metabolismo de los Lípidos/fisiología , Músculo Esquelético/metabolismo , Condicionamiento Físico Animal , Tejido Adiposo Blanco/citología , Animales , Masculino , Músculo Esquelético/citología , Ratas , Ratas WistarRESUMEN
The angiotensin (Ang) converting enzyme 2/Ang-(1-7)/Mas axis has been described to have a beneficial role on metabolic disorders. In the present study, the use of a transgenic rat model that chronically overexpresses Ang-(1-7) enabled us to investigate the chronic effects of this peptide on lipid accumulation in the liver and adipose tissue. The transgenic group showed a marked tendency toward increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and decreased lipoprotein lipase (LPL) expression and activity in epididymal adipose tissue. We also showed that Mas receptor-knockout mice had decreased PPARγ expression in adipose tissue, accompanied by an increase in LPL activity. These results confirm the regulation of adipose tissue LPL activity by Ang-(1-7) and suggest that this occurs independent of PPARγ expression. The reduced adiposity index of transgenic rats, due to the effect of Ang-(1-7), was accompanied by a decrease in lipogenesis. These findings suggest a direct effect of Ang-(1-7) on lipogenesis, independent of the stimulatory effect of insulin. Furthermore, the decreased concentration of triacylglycerol in the liver of transgenic rats may result from increased activity of cytosolic lipases and decreased fatty acid uptake from the adipose tissue, determined from fatty acid-binding protein expression, and hepatic de novo fatty acid synthesis, evaluated by fatty acid synthase expression. The data clearly show that Ang-(1-7) regulates lipid metabolism in the adipose tissue and liver.
Asunto(s)
Tejido Adiposo/metabolismo , Angiotensina I/fisiología , Metabolismo de los Lípidos , Hígado/metabolismo , Fragmentos de Péptidos/fisiología , Adiposidad , Angiotensina I/genética , Animales , Ácidos Grasos/metabolismo , Hipertensión/metabolismo , Insulina/metabolismo , Lipoproteína Lipasa/genética , Lipoproteína Lipasa/metabolismo , Masculino , Ratones , Obesidad/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Fragmentos de Péptidos/genética , ARN Mensajero/genética , Ratas , Ratas Transgénicas , Factores de Tiempo , Triglicéridos/metabolismoRESUMEN
Several studies have demonstrated that a high-fructose (FRUC) diet induces metabolic and haemodynamic abnormalities, known as the metabolic syndrome, which are characterised by obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. In this study, the effect of a FRUC diet (60 % fructose) for 8 weeks on the metabolism of lipids in liver and epididymal adipose tissue from Wistar rats was compared with the AIN-93M diet and the effects of the AIN-93M diet were compared with a chow diet. The FRUC diet induced marked increases in both hepatocyte lipid droplet volume and postprandial serum levels of triacylglycerol (TAG), but reduced the postprandial serum levels of insulin. The AIN-93M diet induced marked increases in the hepatocyte lipid droplet volume and the serum levels of insulin, without affecting the serum levels of TAG. We found that isocaloric substitution of cornstarch, dextrinised cornstarch and sucrose (AIN-93M diet) for fructose did not affect the hepatic VLDL-TAG secretion and adipose tissue glucose uptake, lipolysis and cytosolic lipases activities in rats. However, the high-fructose diet induced a severe steatosis in liver accompanied by a decrease in cytosolic lipases activities. In adipose tissue, the FRUC diet induced a decrease in the lipoprotein lipase activity, and an increase in lipogenesis. FRUC and AIN-93M diets induced changes in lipid homeostasis in liver and adipose tissue by distinct biochemical mechanisms.
Asunto(s)
Tejido Adiposo/efectos de los fármacos , Carbohidratos de la Dieta/administración & dosificación , Fructosa/administración & dosificación , Lipasa/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Tejido Adiposo/enzimología , Animales , Glucemia/metabolismo , Citosol/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/enzimología , Insulina/sangre , Gotas Lipídicas/efectos de los fármacos , Gotas Lipídicas/metabolismo , Hígado/enzimología , Masculino , Ratas , Ratas Wistar , Triglicéridos/metabolismoRESUMEN
The renin-angiotensin system is an important link between metabolic syndrome and cardiovascular diseases. Besides angiotensin II, other angiotensin peptides such as angiotensin-(1-7), have important biological activities. It has been demonstrated that angiotensin-(1-7), acting through the G protein-coupled receptor encoded by the Mas protooncogene have important actions on the cardiovascular system. However, the role of angiotensin-(1-7)-Mas axis in lipidic profile is not well established. In the present study, the adipocyte metabolism was investigated in wild type and FVB/N Mas-deficient male mice. The gene expression of peroxisome proliferator-activated receptor gamma, acetyl-CoA carboxylase and the amount of fatty acid synthase protein were reduced in the Mas-knockout mice. Serum nonesterified fatty acids of Mas-knockout showed a 50% increase in relation to wild type group. Basal and isoproterenol-stimulated lipolysis was similar between the groups, however, a significant decrease of the glycerol release (lipolytic index) in response to insulin was observed in wild type animals, while no effect of the insulin action was observed in a Mas-knockout group. The data suggest that the lack of angiotensin-(1-7) action through Mas receptor alters the response of adipocytes to insulin action. These effects might be related to decreased expression of PPARγ.
Asunto(s)
Adipocitos/fisiología , PPAR gamma/genética , Proteínas Proto-Oncogénicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Adipocitos/efectos de los fármacos , Tejido Adiposo , Animales , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Ácidos Grasos no Esterificados/sangre , Regulación de la Expresión Génica , Glicerol/metabolismo , Insulina/farmacología , Isoproterenol/farmacología , Lipólisis/efectos de los fármacos , Masculino , Ratones , Ratones Noqueados , PPAR gamma/metabolismo , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/genética , Receptores Acoplados a Proteínas G/genéticaRESUMEN
Obesity may represent a state of chronic low-grade inflammation associated with infiltration of adipose tissue by inflammatory cells. Tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1/JE), two important inflammatory cytokines, have been shown to be regulated according to changes in body adiposity. In this study on Swiss mice, we compared the influences of long-term high-carbohydrate (HC) or high-fat (HF) diet on adiposity, glucose tolerance, and secretion of TNF-α and MCP-1/JE by adipose tissue and liver. For 8 weeks, male Swiss mice (7-8 weeks) were fed either standard laboratory rodent diet (control group), HC diet (64% carbohydrate, 19% protein, and 11% fat), or HF diet (45% carbohydrate, 17% protein, and 38% fat), with the latter two diets having no fiber. Oral glucose tolerance test, triacylglycerol (TAG) plasma concentration, and systemic or tissue levels of the two proinflammatory cytokines were determined. Body weight increased by approximately 20% in mice fed the experimental diets compared with mice fed the control diet. Systemically, the hypercaloric diets induced hyperglycemia with impairment in glucose tolerance, elevated circulating TAG levels, and increased plasma concentrations of TNF-α and MCP-1/JE. In the target organs (adipose tissue and liver), both diets increased MCP-1/JE levels. However, the HC diet, but not the HF diet, was able to increase TNF-α concentration in the liver. These results have shown that the nature of nutrients influences the type of proinflammatory cytokines in target organs and may contribute to the comorbidities of obesity.
Asunto(s)
Quimiocina CCL2/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Hígado/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Tejido Adiposo/metabolismo , Adiposidad , Animales , Peso Corporal , Quimiocina CCL2/sangre , Dieta , Prueba de Tolerancia a la Glucosa , Hiperglucemia , Masculino , Ratones , Obesidad/inmunología , Obesidad/metabolismo , Triglicéridos/sangre , Triglicéridos/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVE: Obesity and diabetes remain among the world's most pervasive health problems. Although the importance of angiotensin II for metabolic regulation is well documented, the role of the angiotensin-(1-7)/Mas axis in this process is poorly understood. The aim of this study was to evaluate the effect of increased angiotensin-(1-7) plasma levels in lipid and glucose metabolism using transgenic rats that express an angiotensin-(1-7)-releasing fusion protein, TGR(A1-7)3292 (TGR). METHODS AND RESULTS: The increased angiotensin-(1-7) levels in TGR induced enhanced glucose tolerance, insulin sensitivity, and insulin-stimulated glucose uptake. In addition, TGR presented decreased triglycerides and cholesterol levels, as well as a significant decrease in abdominal fat mass, despite normal food intake. These alterations were accompanied by a marked decrease of angiotensinogen expression and increased Akt in adipose tissue. Furthermore, augmented plasma levels and expression in adipose tissue was observed for adiponectin. Accordingly, angiotensin-(1-7) stimulation increased adiponectin production by primary adipocyte culture, which was blocked by the Mas antagonist A779. Circulating insulin and muscle glycogen content were not altered in TGR. CONCLUSION: These results show that increased circulating angiotensin-(1-7) levels lead to prominent changes in glucose and lipid metabolism.
Asunto(s)
Tejido Adiposo/metabolismo , Angiotensina II/sangre , Glucemia/metabolismo , Metabolismo de los Lípidos , Fragmentos de Péptidos/sangre , Adipocitos/metabolismo , Adiponectina/sangre , Tejido Adiposo/citología , Tejido Adiposo/efectos de los fármacos , Adiposidad , Angiotensina I , Angiotensina II/análogos & derivados , Angiotensina II/genética , Angiotensina II/farmacología , Animales , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Peso Corporal , Células Cultivadas , Colesterol/sangre , Insulina/sangre , Leptina/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Masculino , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/farmacología , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores Acoplados a Proteínas G/metabolismo , Factores de Tiempo , Triglicéridos/sangre , Regulación hacia ArribaRESUMEN
OBJECTIVE: Metabolic syndrome is characterized by the variable coexistence of obesity, hyperinsulinemia, insulin resistance, dyslipidemia, and hypertension. It is well known that angiotensin (Ang) II is importantly involved in the metabolic syndrome. However, the role of the vasodilator Ang-(1-7)/Mas axis is not known. The aim of this study was to evaluate the effect of genetic deletion of the G protein-coupled receptor, Mas, in the lipidic and glycemic metabolism in FVB/N mice. RESEARCH DESIGN AND METHODS: Plasma lipid, insulin, and cytokine concentrations were measured in FVB/N Mas-deficient and wild-type mice. A glucose tolerance test was performed by intraperitoneally injecting d-glucose into overnight-fasted mice. An insulin sensitivity test was performed by intraperitoneal injection of insulin. Uptake of 2-deoxy-[(3)H]glucose by adipocytes was used to determine the rate of glucose transport; adipose tissue GLUT4 was quantified by Western blot. Gene expression of transforming growth factor (TGF)-beta, type 1 Ang II receptor, and angiotensinogen (AGT) were measured by real-time PCR. RESULTS: Despite normal body weight, Mas-knockout (Mas-KO) mice presented dyslipidemia, increased levels of insulin and leptin, and an approximately 50% increase in abdominal fat mass. In addition, Mas gene-deleted mice presented glucose intolerance and reduced insulin sensitivity as well as a decrease in insulin-stimulated glucose uptake by adipocytes and decreased GLUT4 in adipose tissue. Mas(-/-) presented increased muscle triglycerides, while liver triglyceride levels were normal. Expression of TGF-beta and AGT genes was higher in Mas-KO animals in comparison with controls. CONCLUSIONS: These results show that Mas deficiency in FVB/N mice leads to dramatic changes in glucose and lipid metabolisms, inducing a metabolic syndrome-like state.
Asunto(s)
Glucemia/metabolismo , Insulina/sangre , Lípidos/sangre , Proteínas Proto-Oncogénicas/deficiencia , Receptores Acoplados a Proteínas G/deficiencia , Adipocitos/metabolismo , Tejido Adiposo/anatomía & histología , Tejido Adiposo/fisiología , Animales , Transporte Biológico , Peso Corporal , Citocinas/sangre , Ingestión de Energía , Epidídimo/patología , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Masculino , Síndrome Metabólico/genética , Síndrome Metabólico/patología , Ratones , Ratones Noqueados , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/genética , Receptores Acoplados a Proteínas G/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Triglicéridos/sangreRESUMEN
The acute effects of physiological levels of leptin (10 ng ml(-1)) and insulin (20 microU ml(-1)) on hepatic gluconeogenesis and ketogenesis were compared. Leptin or insulin alone decreased (p<0.05) the activation of hepatic glucose, L-lactate and urea production from L-alanine. However, the hepatic glucose production was not modified if leptin was combined with insulin. These results indicated that both, i.e. leptin and insulin, could promote a non-additive reduction in the rate of catabolism of L-alanine. However, in contrast with insulin (p<0.05), leptin did not inhibit the activation of hepatic glucose production from pyruvate or glycerol. On the other hand, activation of hepatic production of acetoacetate and beta-hydroxybutyrate from octanoate was not affected by leptin or insulin. Thus, our data demonstrate that the acute effect of leptin on hepatic metabolism was partially similar to insulin (activation of glucose production from L-alanine and activation of acetoacetate or beta-hydroxybutyrate production from octanoate) and partially different from insulin (activation of glucose production from pyruvate or glycerol).