RESUMO
PURPOSE: Rats fed a long-term sucrose-rich diet (SRD) developed adipose tissue dysfunction. In the adipose tissue of these SRD-fed rats, the present study analyzed the possible beneficial effects of dietary Salba (chia) seeds in improving or reversing the depletion of antioxidant defenses, changes in pro-inflammatory cytokines and ROS production. METHODS: Wistar rats were fed a SRD for 3 months. After that, half of the animals continued with the SRD until month 6, while in the other half, corn oil was replaced by chia seeds for 3 months (SRD + chia). A reference group consumed a control diet all the time. RESULTS: Compared with the SRD-fed rats, the animals fed a SRD + chia showed a reduction in epididymal fat pad weight; the activities of antioxidant enzymes CAT, SOD and GPx returned to control values, while GR significantly improved; mRNA GPx increased, and both mRNA SOD and the redox state of glutathione returned to control values; a significant increase in the expression of Nrf2 was recorded. These results were accompanied by a decrease in XO activity and ROS contents as well as plasma IL-6 and TNF-α levels. Chia seeds reversed the decrease in PPARγ protein mass level and increased the n-3/n-6 fatty acids ratio of membrane phospholipids. Besides, dyslipidemia and insulin sensitivity were normalized. CONCLUSION: This study provides new information concerning some mechanisms related to the beneficial effects of dietary chia seeds in reversing adipose tissue oxidative stress and improving the adipose tissue dysfunction induced by a SRD.
Assuntos
Tecido Adiposo/fisiopatologia , Citocinas/fisiologia , Dislipidemias/dietoterapia , Estresse Oxidativo/fisiologia , PPAR gama/fisiologia , Salvia , Tecido Adiposo/química , Tecido Adiposo/patologia , Animais , Antioxidantes/metabolismo , Dieta , Sacarose Alimentar/efeitos adversos , Dislipidemias/patologia , Dislipidemias/fisiopatologia , Ingestão de Energia , Ácidos Graxos/administração & dosagem , Ácidos Graxos/análise , Inflamação , Resistência à Insulina/fisiologia , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , SementesRESUMO
The present work analyzes the effects of dietary chia seeds during postnatal life in offspring exposed to a sucrose-rich diet (SRD) from utero to adulthood. At weaning, chia seed (rich in α-linolenic acid) replaced corn oil (rich in linoleic acid) in the SRD. At 150 days of offspring life, anthropometrical parameters, blood pressure, plasma metabolites, hepatic lipid metabolism and glucose homeostasis were analyzed. Results showed that chia was able to prevent the development of hypertension, liver steatosis, hypertriglyceridemia and hypercholesterolemia. Normal triacylglycerol secretion and triacylglycerol clearance were accompanied by an improvement of de novo hepatic lipogenic and carnitine-palmitoyl transferase-1 enzymatic activities, associated with an accretion of n-3 polyunsaturated fatty acids in the total composition of liver homogenate. Glucose homeostasis and plasma free fatty acid levels were improved while visceral adiposity was slightly decreased. These results confirm that the incorporation of chia seed in the diet in postnatal life may provide a viable therapeutic option for preventing/mitigating adverse outcomes induced by an SRD from utero to adulthood.
Assuntos
Sacarose Alimentar/efeitos adversos , Dislipidemias/prevenção & controle , Fígado Gorduroso/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Salvia/química , Ácido alfa-Linolênico/administração & dosagem , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Grão Comestível/química , Ácidos Graxos não Esterificados/sangue , Feminino , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Desmame , Ácido alfa-Linolênico/farmacologiaRESUMO
PURPOSE: The present study analyzes the effect of the replacement of dietary casein by soy protein on the mechanisms underlying dyslipidemia, liver steatosis and altered glucose and lipid metabolism in the skeletal muscle which developed in rats fed long-term a sucrose-rich diet (SRD). METHODS: Wistar rats were fed a SRD for 4 months. From months 4 to 8, half the animals continued with the SRD, and the other half were fed a SRD in which the source of protein casein was replaced by soy. The control group received a diet with cornstarch as source of carbohydrate. RESULTS: Compared to SRD-fed animals, the rats fed soy showed: A--in the liver: reduction of triglyceride and cholesterol storage and decreased steatosis; normalization of mature forms of the protein mass levels of SREBP-1 and the activities of lipogenic enzymes, while the protein mass level of PPAR-α and fatty acid oxidase activity increased. B-in the gastrocnemius muscle: normalization of the enhanced lipid storage and the altered glucose oxidation, improving glucose phosphorylation; decreasing protein mass level of nPKCθ in the membrane fraction; reversion of the impaired insulin-stimulated glucose transporter Glut-4, and glucose-6-phosphate and glycogen concentrations. Besides, dyslipidemia and glucose homeostasis returned to control values. CONCLUSIONS: This study provides new information concerning some key mechanisms related to the effect of dietary soy on hepatic lipid metabolism and insulin action in the skeletal muscle in the presence of pre-existing dyslipidemia and insulin resistance induced by a SRD.
Assuntos
Sacarose Alimentar/efeitos adversos , Dislipidemias/dietoterapia , Resistência à Insulina , Fígado/metabolismo , Músculo Esquelético/metabolismo , Proteínas de Soja/administração & dosagem , Animais , Glicemia/metabolismo , Colesterol/sangue , Sacarose Alimentar/administração & dosagem , Ácidos Graxos não Esterificados/sangue , Fígado Gorduroso/dietoterapia , Transportador de Glucose Tipo 4/metabolismo , Glucose-6-Fosfato/metabolismo , Glicogênio/metabolismo , Insulina/sangue , Metabolismo dos Lipídeos , Masculino , PPAR alfa/metabolismo , Ratos , Ratos Wistar , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/sangue , Aumento de PesoRESUMO
This work reports the effect of dietary Salba (chia) seed rich in n-3 α-linolenic acid on the morphological and metabolic aspects involved in adipose tissue dysfunction and the mechanisms underlying the impaired glucose and lipid metabolism in the skeletal muscle of rats fed a sucrose-rich diet (SRD). Rats were fed a SRD for 3 months. Thereafter, half the rats continued with SRD while in the other half, corn oil (CO) was replaced by chia seed for 3 months (SRD+chia). In control group, corn starch replaced sucrose. The replacement of CO by chia seed in the SRD reduced adipocyte hypertrophy, cell volume and size distribution, improved lipogenic enzyme activities, lipolysis and the anti-lipolytic action of insulin. In the skeletal muscle lipid storage, glucose phosphorylation and oxidation were normalized. Chia seed reversed the impaired insulin stimulated glycogen synthase activity, glycogen, glucose-6-phosphate and GLUT-4 protein levels as well as insulin resistance and dyslipidemia.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Suplementos Nutricionais , Dislipidemias/dietoterapia , Músculo Esquelético/efeitos dos fármacos , Salvia/química , Sementes/química , Ácido alfa-Linolênico/administração & dosagem , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Tamanho Celular , Óleo de Milho/administração & dosagem , Dislipidemias/induzido quimicamente , Dislipidemias/metabolismo , Dislipidemias/patologia , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Glucose-6-Fosfato/metabolismo , Glicogênio Sintase/metabolismo , Insulina/farmacologia , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Fosforilação Oxidativa/efeitos dos fármacos , Ratos , Ratos Wistar , Sementes/metabolismo , Sacarose/administração & dosagem , Sacarose/efeitos adversosRESUMO
This study evaluates some possible mechanisms behind the beneficial effects of dietary fish oil (FO) on ß cell dysfunction in rats fed a sucrose-rich diet (SRD). Rats were fed a SRD for 6 months. Thereafter, half the rats received a SRD in which corn oil was partially replaced by FO up to 8 months. The other half continued consuming the SRD up to 8 months. A control group was fed a control diet throughout the experimental period. In isolated islets of SRD-fed rats dietary FO normalized the reduced glucose phosphorylation, the altered glucose oxidation, the triglyceride content, the increased protein mass levels of peroxisome proliferator-activated receptor γ (PPARγ) and uncoupling protein 2 without changes in GLUT2 and PPARα. These finding suggest that the changes mentioned above could be involved in the normalization of the altered glucose-stimulated insulin secretion pattern in this nutritional model of dyslipidemia and insulin resistance.
Assuntos
Dislipidemias/metabolismo , Óleos de Peixe/farmacologia , Transportador de Glucose Tipo 2/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Canais Iônicos/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Proteínas Mitocondriais/metabolismo , PPAR gama/metabolismo , Animais , Masculino , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Proteína Desacopladora 2RESUMO
A sucrose-rich diet generates time-dependent metabolic disorders similar to those found in diabetes type 2. After 8 month (mo) this diet evoked in the rat an increase of blood glucose, free fatty acids (FFA) and triacylycerides (TG) without insulin modification, an interruption of liver stearoyl-CoA desaturase-1 (SCD-1) mRNA and activity increase found at 6 mo, and an enhacement of Delta6 and Delta5 desaturase mRNA and Delta6 activity. We found that the administration of troglitazone (TRO), a peroxisome-proliferator-activated receptors gamma (PPAR-gamma) agonist, for 2 mo normalized plasma FFA, TG, and glucose without altering the insulinemia. It depressed liver SCD-1 mRNA in both control and sucrose-fed rats, decreasing the 18:1n-9/18:0 ratio in serum and liver lipids, and eliminated the increasing effect on mRNA and activity of Delta6 and Delta5 desaturases. These findings evidence again that desaturases are not affected through an insulin resistant effect evoked by the sucrose-rich diet and TRO recovers the altered metabolic plasma parameters as it corresponds to a PPAR-gamma agonist, but its effect on hepatic desaturases can not be attributed to a direct action on liver by PPAR-gamma, insulin, and even by an insulin sensitizing mechanism, suggesting it would be evoked indirectly through hepatic PPAR-alpha deactivation induced by the FFA decrease.
Assuntos
Cromanos/farmacologia , Carboidratos da Dieta/farmacologia , Modelos Animais de Doenças , Ácidos Graxos Dessaturases/metabolismo , Resistência à Insulina , Sacarose/farmacologia , Tiazolidinedionas/farmacologia , Animais , Carboidratos da Dieta/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Microssomos Hepáticos/metabolismo , Plasma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Sacarose/administração & dosagem , TroglitazonaRESUMO
This study aimed to determine the relative importance of different functional and morphological pancreatic changes induced by the chronic administration of a sucrose-rich diet (SRD) to maintain normal glucose homeostasis. Male Wistar rats were fed either sucrose (SRD) or starch (CD) for 6 and 12 months. At both periods, serum glucose and triacylglycerol levels were significantly higher (P<0.05; paired and unpaired Student's t-test) in SRD rats. Serum insulin levels were significantly lower in SRD only at 12 months. At 6 months, the insulin secretion dose-response curve in SRD rats showed a shift to the left that was no longer observed at 12 months, when SRD islets decreased their response to 16 mM glucose. At 6 months, SRD rats showed a significant increase in beta-cell volume density (Vvi) and islet cell replication rate, together with a decrease in beta-cell apoptotic rate. Changes were not detected in the percentage of PDX-1- and islet neogenesis associated protein (INGAP)-positive cells. Conversely, at 12 months, there was a significant decrease in beta-cell Vvi and in the percentage of PDX-1-positive cells; the islet cell replication rate was not modified, and the number of apoptotic beta-cells increased significantly. No signs of increased neogenesis or INGAP-positive cells were recorded at any period in SRD rats. Our results show that SRD rats are unable to develop functional and morphological pancreatic reactive changes sufficient to maintain normal glucose and triacylglycerol levels for a long period. Such failure could be ascribed to their inability to increase the rate of neogenesis and of INGAP production.
Assuntos
Carboidratos da Dieta/administração & dosagem , Insulina/metabolismo , Ilhotas Pancreáticas/fisiologia , Adaptação Fisiológica , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Secreção de Insulina , Masculino , Proteínas Associadas a Pancreatite , Ratos , Ratos Wistar , Amido/administração & dosagem , Sacarose/administração & dosagem , Fatores de TempoRESUMO
The aim of this work was to study the effect of the administration of cod liver oil on the non-oxidative and oxidative fate of glucose metabolism in the skeletal muscle of normal rats. To achieve this goal, the gastrocnemius was examined regarding glucose oxidation, glycogen synthase activity and glycogen storage both at baseline and during euglycemic hyperinsulinemic clamping. The results show that dietary fish oil decreases plasma insulin levels without alteration in glucose homeostasis (at baseline). In addition, the observed enhancement in whole body glucose utilization during clamping suggests an increased peripheral insulin sensitivity. Furthermore, under insulin-stimulated glucose disposal, an enhancement in the glycolytic pathway (increased levels of muscle glucose-6-phosphate and plasma lactate) rather than changes in the oxidation (pyruvate dehydrogenase complex) and storage components of glucose metabolism was observed in the skeletal muscle of rats fed dietary fish oil. These results coupled with the hypolipidemic effects of fish oil may have implications for the prevention and/or management of some pathological states manifested by insulin resistance with or without dyslipidemia.
Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Óleos de Peixe/farmacologia , Glucose/metabolismo , Insulina/metabolismo , Músculo Esquelético/fisiologia , Animais , Óleo de Fígado de Bacalhau/farmacologia , Óleo de Milho/farmacologia , Ácidos Graxos/administração & dosagem , Técnica Clamp de Glucose , Glucose-6-Fosfato/metabolismo , Glicogênio/metabolismo , Glicogênio Sintase/efeitos dos fármacos , Masculino , Proteínas Quinases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases , Piruvato Desidrogenase Quinase de Transferência de Acetil , Complexo Piruvato Desidrogenase/efeitos dos fármacos , Ratos , Ratos Wistar , Valores de Referência , Triglicerídeos/metabolismoRESUMO
In this work, we studied the effect of a short-term (3 wk) and a long-term (15 wk) administration of a sucrose-rich diet (SRD) to Wistar rats on the morphological aspects and metabolic function of the epididymal adipose tissue that may contribute to the mechanism underlying the impaired glucose homeostasis and insulin resistance. The present work showed the following. 1) There was both a moderate increase of basal lipolysis and a decrease of the antilipolytic action of insulin in the adipocytes of rats fed a SRD for 3 wk. Neither size alterations nor increases in adipose tissue mass were recorded in this period. 2) There was a significant (P < 0.05) increase of epididymal weight after 15 wk on a SRD as well as a hypertrophy of adipocytes with a clear alteration in the cell size distribution. This was accompanied by a significant increase (P < 0.05) of basal and stimulated lipolysis and a marked decrease (P < 0.05) of the antilipolytic action of insulin. Moreover, these changes appear together with a worsening of both impaired glucose homeostasis and insulin resistance. Our results also indicate that the length of time on the SRD plays an important role in the evolution of the adiposity and metabolic changes observed in the fat pad. Furthermore, the latter precedes the detection of adiposity.
Assuntos
Adipócitos/efeitos dos fármacos , Sacarose/farmacologia , Adipócitos/metabolismo , Adipócitos/ultraestrutura , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/fisiologia , Animais , Contagem de Células , Dieta , Ingestão de Alimentos , Técnica Clamp de Glucose , Glicerol/metabolismo , Hiperinsulinismo/metabolismo , Técnicas In Vitro , Resistência à Insulina/fisiologia , Lipase Lipoproteica/metabolismo , Masculino , Tamanho do Órgão/fisiologia , Ratos , Ratos Wistar , Esterol Esterase/metabolismo , Aumento de Peso/fisiologiaRESUMO
Rats fed a sucrose-rich diet ([SRD] 63% wt/wt) up to 270 days develop stable hypertriglyceridemia, impaired glucose tolerance, and insulin insensitivity. The aim of the present study is to investigate whether the hypoglycemic agent troglitazone introduced as a pharmacologic intervention could improve and/or reverse the whole-body insulin insensitivity and related abnormalities present after feeding normal rats with a SRD long-term. For this purpose, male Wistar rats were fed a SRD for 210 days. While half of the animals continued with this diet for up to 270 days, troglitazone (0.2 g/dL wt/wt) was added to the SRD of the other half for up to 270 days. Troglitazone markedly reduced in vivo the hepatic triglyceride secretion rate (TGSR) and enhanced its removal from the circulation, leading to a normalization of plasma triglyceride levels. It also normalized the whole-body peripheral insulin resistance, the glucose homeostasis, and the elevated free fatty acids (FFAs) without detectable changes in plasma insulin levels. The clear alteration of the biphasic pattern of glucose-stimulated insulin secretion in the in vitro perfused beta-cell islets of rats fed the SRD long-term (270 days) was also completely normalized when the SRD was supplemented with troglitazone for 2 months. The normalization of the altered patterns of glucose-stimulated insulin secretion, as well as the enhancement of peripheral insulin sensitivity without detectable changes in plasma insulin, might be largely a result of the significant action of troglitazone in the decrease of circulating lipids and enhancement of whole-body glucose metabolism.