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.
Assuntos
Cromanos/farmacologia , Glucose/farmacologia , Hipertrigliceridemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Tiazóis/farmacologia , Tiazolidinedionas , Animais , Peso Corporal/efeitos dos fármacos , Sacarose Alimentar/administração & dosagem , Ácidos Graxos não Esterificados/sangue , Secreção de Insulina , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Triglicerídeos/metabolismo , TroglitazonaRESUMO
In the present study we investigated: (1) the contribution of the skeletal muscle to the mechanisms underlying the impaired glucose homeostasis and insulin sensitivity present in dyslipemic rats fed a sucrose-rich diet (SRD) over a long period of time and (2) the effect of fish oil on these parameters when there was a stable hypertriglyceridemia before the source of fat (corn oil) in the diet was replaced by isocaloric amounts of cod liver oil. Our results show an increased triglyceride content in the gastrocnemius muscle with an impaired capacity for glucose oxidation in the basal state and during euglycemic clamp. This was mainly due to a decrease of the active form of pyruvate dehydrogenase complex (PDHa) and an increase of PDH kinase activities. Hyperglycemia, normoinsulinemia, and diminished peripheral insulin sensitivity also were found. Even though there were no changes in the insulin levels, the former metabolic abnormalities were completely reversed when the source of fat was changed from corn oil to cod liver oil. The data also suggest that in the gastrocnemius muscle of rats fed a SRD over an extended period, an increased availability and oxidation of the lipid fuel, which in turn impairs the glucose oxidation, contributes to the abnormal glucose homeostasis and to the peripheral insulin insensitivity. Moreover, the parallel effect on insulin sensitivity, glucose, and lipid homeostasis attained through the manipulation of dietary fat (n-3) in the SRD suggests a role of n-3 fatty acid in the management of dyslipidemia and insulin resistance.
RESUMO
Several reports have demonstrated that high-protein diets may have beneficial effects on experimental models of diabetes and have raised the possibility that branched-chain amino acids could play a role in these protective effects. We investigated the effect of a normoproteic, branched-chain amino acid-enriched diet (experimental diet) on insulin secretion from C57BL/6N mice transferred with splenocytes from diabetic syngeneic donors. Mice previously fed with the experimental or control diet received three intraperitoneal injections, every other day, of 5 x 107 viable mononuclear splenocytes obtained from control or diabetic donors. Results showed that mice fed with the experimental diet and transferred with "diabetic" splenocytes presented: i) normoglycemia, and (ii) significantly higher levels in both phases of glucose-induced insulin secretion and normal values of arginine-glucose-induced insulin secretion. To evaluate the in vitro cellular immune aggression, dispersed mouse islet cells were co-cultured with splenocytes from syngeneic diabetic mice. First, dispersed islet cells from mice on the experimental or control diet were co-cultured with splenocytes from control or diabetic mice on a commercial diet. In the presence of "diabetic splenocytes, dispersed islet cells from mice on the experimental diet presented a significantly lower in vitro cellular immune aggression. On the other hand, "diabetic" splenocytes from mice fed with the experimental diet produced a significantly reduced cellular immune aggression on dispersed islet cells. Our results showed that feeding branched-chain amino acids increased the capacity of beta cells to withstand a functional assault and diminished the extent of in vitro cellular immune aggression.
Assuntos
Aminoácidos de Cadeia Ramificada/farmacologia , Diabetes Mellitus Experimental/imunologia , Suplementos Nutricionais , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Transfusão de Linfócitos , Linfócitos/imunologia , Baço/imunologia , Animais , Células Cultivadas , Técnicas de Cocultura , Glucose/farmacologia , Imunidade Celular/efeitos dos fármacos , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transplante Isogênico/imunologia , Transplante Isogênico/fisiologiaRESUMO
Male Wistar rats chronically (15 weeks) fed a sucrose-rich diet (SRD; 63% w/w) developed hypertriglyceridemia and impaired glucose homeostasis. Hearts from these animals were isolated and perfused using the Langendorff recirculating method. Glucose at levels similar to those found in the animal in vivo was used as the only exogenous substrate. The hearts were perfused for 30 minutes in the presence or absence of insulin (30 mU/mL) in the perfusion medium. In the absence of the hormone, glucose uptake was impaired and the glucose utilization was reduced, with a significant increase of lactate release. Glucose oxidation, which was estimated from the activation state of the enzyme pyruvate dehydrogenase complex (PDHc), was depressed mainly due to both an increase of PDH kinase and a decrease of PDHa (active form of PDHc) activities. Although the addition of insulin in the perfusion medium improved the above parameters, it was unable to normalize them. The present results suggest that at least two different mechanisms might contribute to insulin resistance and to the impaired glucose metabolism in the perfused hearts of the dyslipemic SRD-fed animals: (1) reduced basal and insulin-stimulated glucose uptake and its utilization or (2) increased availability and oxidation of lipids (low PDHa and high PDH kinase activities), which in turn decrease glucose uptake and utilization. Thus, this nutritional experimental model may be useful to study how impaired glucose homeostasis, increases plasma free fatty acid levels and hypertriglyceridemia could contribute to heart tissue malfunction.
RESUMO
Rats chronically fed (15 weeks) a sucrose-rich diet (SRD) developed hypertriglyceridemia (hyperTg), increased plasma free fatty acids (FFA), impaired glucose homeostasis and insulin insensitivity. An increase of Tg and glycogen (Gly) in heart muscle was also observed. HyperTg with altered glucose metabolism could have profound effects on myocardial glucose utilization. To test this hypothesis male Wistar rats were fed a semi-synthetic SRD (w/w: 62.5% sucrose, 8% corn-oil, 17% protein), and the control group (CD) received the same semi-synthetic diet, except that sucrose was replaced with starch for 90 days. At that time, the hearts from these animals were isolated and perfused for 30 min in the presence or absence of insulin (30 mU/ml). Levels of the exogenous substrates were similar to those found in the plasma of the animal in vivo in both dietary groups (glucose 8.5 mM, palmitate 0.8 mM in SRD and glucose 5-5 mM, palmitate 0.3 mM in CD). In the absence of insulin glucose uptake was reduced (40%) and lactate release was increased (50%) in SRD hearts. Glucose oxidation was depressed mainly due to both, an increase of PDH kinase and a decrease of 60% of PDHa (active form of PDHc). Insulin in the perfusion medium improved only glucose uptake. The results suggest that at least two different mechanisms might contribute to insulin resistance and to impaired glucose metabolism in the perfused hearts of dyslipemic SRD fed rats: 1) reduced basal and insulin-stimulated glucose uptake and its utilization and 2) increased availability and oxidation of lipids (low PDHa and PDH kinase activities), which in turn decreased glucose uptake and utilization. Thus, this experimental model may be useful to study how impaired glucose homeostasis, increased plasma FFA and hyperTg could contribute to heart tissue malfunction.
Assuntos
Glucose/metabolismo , Hiperlipidemias/metabolismo , Insulina/fisiologia , Miocárdio/metabolismo , Análise de Variância , Animais , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Resistência à Insulina , Masculino , Miocárdio/enzimologia , Complexo Piruvato Desidrogenase/metabolismo , Piruvato Quinase/metabolismo , Ratos , Ratos Wistar , Aumento de PesoRESUMO
Rats chronically fed (15 weeks) a sucrose-rich diet (SRD) developed hypertriglyceridemia (hyperTg), increased plasma free fatty acids (FFA), impaired glucose homeostasis and insulin insensitivity. An increase of Tg and glycogen (Gly) in heart muscle was also observed. HyperTg with altered glucose metabolism could have profound effects on myocardial glucose utilization. To test this hypothesis male Wistar rats were fed a semi-synthetic SRD (w/w: 62.5
sucrose, 8
corn-oil, 17
protein), and the control group (CD) received the same semi-synthetic diet, except that sucrose was replaced with starch for 90 days. At that time, the hearts from these animals were isolated and perfused for 30 min in the presence or absence of insulin (30 mU/ml). Levels of the exogenous substrates were similar to those found in the plasma of the animal in vivo in both dietary groups (glucose 8.5 mM, palmitate 0.8 mM in SRD and glucose 5-5 mM, palmitate 0.3 mM in CD). In the absence of insulin glucose uptake was reduced (40
) and lactate release was increased (50
) in SRD hearts. Glucose oxidation was depressed mainly due to both, an increase of PDH kinase and a decrease of 60
of PDHa (active form of PDHc). Insulin in the perfusion medium improved only glucose uptake. The results suggest that at least two different mechanisms might contribute to insulin resistance and to impaired glucose metabolism in the perfused hearts of dyslipemic SRD fed rats: 1) reduced basal and insulin-stimulated glucose uptake and its utilization and 2) increased availability and oxidation of lipids (low PDHa and PDH kinase activities), which in turn decreased glucose uptake and utilization. Thus, this experimental model may be useful to study how impaired glucose homeostasis, increased plasma FFA and hyperTg could contribute to heart tissue malfunction.
RESUMO
The aim of the present investigation was to study normal rats fed a sucrose-rich diet (SRD) for a prolonged period (up to 30 weeks) (1) to obtain additional data on the hormonal and metabolic patterns induced by this treatment and (2) to provide information on changes taking place in the pancreatic islet cell populations. We found that long-term feeding with a SRD resulted in a steady state of hypertriglyceridemia and hyperglycemia in which insulin levels remained unchanged and unable to compensate for the increased demands of the developing metabolic changes. The endocrine pancreas showed a significant increase of both islet number and B-cell area, as well as changes in the profile of islet cell distribution. However, these changes were not accompanied by an increase in the pancreatic content of immunoreactive insulin (IRI). It may therefore be postulated that the newly emerged B-cell mass has some sort of derangement with the increased insulin demand resulting from insulin resistance induced by the long-term SRD feeding. Thus, feeding a SRD to normal rats may prove to be an attractive animal model for studying the role of environmental nutritional factors in the unsettled issue of the relationship between insulin resistance and relative insulin deficiency. The model might provide key information for understanding the pathophysiology of human diseases such as type II diabetes, dyslipidemia, and a number of entities included in so-called syndrome X.
Assuntos
Ilhotas Pancreáticas/metabolismo , Sacarose/administração & dosagem , Animais , Peso Corporal , Comportamento Alimentar , Teste de Tolerância a Glucose , Imuno-Histoquímica , Insulina/metabolismo , Ilhotas Pancreáticas/anatomia & histologia , Masculino , Ratos , Ratos WistarRESUMO
A sucrose-rich diet (SRD) causes hypertriglyceridemia in nonpregnant rats. To determine whether a SRD further enhances gestational hypertriglyceridemia, female rats were divided into the following two groups: 1) rats fed a SRD (63 g sucrose/100 g), and 2) rats that received the same diet except that the sucrose was replaced by an equal amount of cornstarch (CD). Half of the rats were mated and studied at d 20 of gestation. Body weight increase did not differ between virgin rats fed either diet, but the final body weight of pregnant rats fed SRD was lower than that of rats fed CD due to fewer fetuses per litter and lower fetal and placental weights. The SRD enhanced plasma glucose and insulin concentrations in virgin but not in pregnant rats; plasma triglycerides and FFA concentrations and the rate of triglyceride secretion into the plasma were higher in pregnant than in virgin rats fed SRD, but the increase in liver triglycerides due to SRD was higher in virgin rats. Both removal rate of a fat emulsion and adipose tissue lipoprotein lipase activity (LPL) were lower in virgin rats fed SRD than in those fed CD. They were lower in pregnant than in virgin rats fed CD. Placental and fetal liver triglyceride concentration and placental LPL were higher in rats fed SRD than in those fed CD. Both the increased triglyceride secretion by the liver and the decreased triglyceride removal from blood resulting in maternal hypertriglyceridemia may contribute to the negative effect of SRD on the developing fetus.
Assuntos
Sacarose Alimentar/farmacologia , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Prenhez/metabolismo , Triglicerídeos/metabolismo , Tecido Adiposo/química , Tecido Adiposo/enzimologia , Animais , Glicemia/análise , Sacarose Alimentar/administração & dosagem , Desenvolvimento Embrionário e Fetal/fisiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Insulina/sangue , Lipase Lipoproteica/análise , Fígado/química , Fígado/embriologia , Fígado/metabolismo , Placenta/química , Placenta/enzimologia , Gravidez , Prenhez/sangue , Distribuição Aleatória , Ratos , Ratos Wistar , Triglicerídeos/análise , Triglicerídeos/sangueRESUMO
The aim of this study was to investigate the relationship between the lipid-lowering effects of fish oils and concomitant consequences on glucose tolerance and insulin sensitivity in an experimental animal model of hypertriglyceridemia induced by high sucrose intake. To achieve this goal, male Wistar rats were fed a semi-synthetic sucrose rich diet (SRD) (w/w: 62.3% sucrose, 8% corn oil, 17% protein) for 90 days. At the time, a well established and permanent hypertriglyceridemia accompanied by glucose intolerance was present. After that, one half of the animals continued on the SRD up to 120 days. The other half received an SRD in which the source of fat was substituted by cod liver oil (w/w 7% CLO plus 1% corn oil) from day 90 to 120 (SRD+CLO). Control rats were fed a semi-synthetic diet (CD) (w/w: 62.5% corn starch, 8% corn oil, 17% protein) throughout the 120 days experimental period. Results obtained after the experimental period show that the hypertriglyceridemia and glucose intolerance ensuing long term feeding normal rats with a sucrose-rich diet could be completely reversed mediating no change in circulating insulin levels by shifting the source of fat in the diet from corn oil to cod liver oil. These findings suggest that manipulation of dietary fats may play a role in the management of the lipid disorders associated with glucose intolerance and insulin resistance.
Assuntos
Óleo de Fígado de Bacalhau/uso terapêutico , Carboidratos da Dieta , Gorduras Insaturadas na Dieta/uso terapêutico , Intolerância à Glucose/tratamento farmacológico , Glucose , Hiperlipidemias/tratamento farmacológico , Triglicerídeos/sangue , Animais , Glicemia , Peso Corporal , Ingestão de Alimentos , Emulsões Gordurosas Intravenosas/administração & dosagem , Intolerância à Glucose/induzido quimicamente , Teste de Tolerância a Glucose , Hiperlipidemias/induzido quimicamente , Insulina/sangue , Resistência à Insulina , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Triglicerídeos/análiseRESUMO
The effect of omega-3 fatty acids derived from fish and marine mammals on subjects with normal glucose tolerance is still unclear. The aim of the present study was to test whether the hypolipidemia that follows the chronic administration of cod liver oil, rich in polyunsaturated fatty acids (omega-3), to normal rats is accompanied by changes in glucose metabolism, insulin secretion and sensitivity, and pancreatic insulin content. To achieve this goal, male Wistar rats were fed with a semisynthetic diet (w/w): 62.5% cornstarch, 7% cod liver oil plus 1% corn oil, and 17% protein (CD + CLO). Control rats were fed with the same semisynthetic diet with the only exception that the source of fat was 8% (w/w) corn oil (CD). Both diets were administered ad libitum for 1 month. At the end of the experimental period, the results obtained were as follows (mean +/- SEM): serum triacylglycerol (mM): CD + CLO 0.21 +/- 0.04 vs. CD 0.58 +/- 0.05 (p < 0.05); free fatty acids (microM): CD + CLO 257 +/- 20 vs. CD 288 +/- 22 (p = NS); total cholesterol (mM): CD + CLO 1.13 +/- 0.09 vs. CD 1.82 +/- 0.06 (p < 0.05); high-density lipoprotein cholesterol (mM): CD + CLO 0.58 +/- 0.08 vs. CD 1.07 +/- 0.04 (p < 0.05); plasma glucose (mM): CD + CLO 6.30 +/- 0.29 vs. CD 6.28 +/- 0.10 (p = NS); liver triacylglycerol (mumol/liver): CD + CLO 104.1 +/- 11.4 vs. CD 136.8 +/- 4.3 (p < 0.05); glycogen (mumol/g wet weight): CD + CLO 298.3 +/- 21.0 vs. CD 297.0 +/- 19.0 (p = NS); glucose-6-phosphate dehydrogenase (U/liver): CD + CLO 37.9 +/- 2.2 vs. CD 58.8 +/- 5.0 (p < 0.05); triacylglycerol secretion (nmol/min/100 g body weight): CD + CLO 101.0 +/- 2.0 vs. CD 166.0 +/- 9.7 (p < 0.01); removal of fat emulsion (K2% min-1): CD + CLO 15.0 x 10(-2) +/- 0.8 x 10(-2) vs. CD 8.2 x 10(-2) +/- 0.2 x 10(-2) (p < 0.01); intravenous glucose tolerance (kg 10(-2): CD + CLO 2.68 +/- 0.37 vs. CD 2.70 +/- 0.14 (p = NS); immunoreactive insulin (microU/ml/ min): with the area under the curve between 0 and 30 min CD + CLO 544 +/- 60 vs. CD 1,050 +/- 38 (p < 0.05), with the area under the curve between 0 and 60 min CD + CLO 1,188 +/- 150 vs. CD 2,160 +/- 137 (p < 0.05), and pancreas insulin content (microU/mg pancreas): CD + CLO 1.85 +/- 0.29 vs. CD 2.04 +/- 0.12 (p = NS). In conclusion, the present study shows that the strong hypolipidemic effect produced by the administration of low doses of fish oil to normal rats is accompanied by a significant reduction of plasma insulin levels without changes in glucose tolerance. Since no changes in pancreatic insulin content were observed, lower plasma insulin levels, both basal and after an intravenous glucose challenge, may be the result of an increased peripheral insulin sensitivity in normoglycemic animals.
Assuntos
Óleos de Peixe/farmacologia , Resistência à Insulina/fisiologia , Insulina/análise , Insulina/metabolismo , Pâncreas/química , Animais , Área Sob a Curva , Glicemia/análise , Colesterol/sangue , HDL-Colesterol/sangue , Óleo de Milho/farmacologia , Relação Dose-Resposta a Droga , Ingestão de Alimentos/fisiologia , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/administração & dosagem , Glucose/metabolismo , Teste de Tolerância a Glucose , Glucosefosfato Desidrogenase/análise , Glicogênio/sangue , Insulina/sangue , Secreção de Insulina , Lipídeos/sangue , Fígado/química , Masculino , Ratos , Ratos Wistar , Triglicerídeos/sangue , Aumento de Peso/fisiologiaRESUMO
Long term feeding a sucrose-rich diet (SRD) to normal Wistar rats led to multiphasic changes in the activity of the pyruvate dehydrogenase complex (PDH), characterized by a significant decrease in PDHa (active form) in the short term on SRD (3 weeks) when compared to control rats fed the standard chow (STD). Although PDHa returned spontaneously to control values in the medium term (6-8 weeks) on SRD, an even more pronounced decrease was recorded when rats were kept long term on the SRD (15 weeks). Low PDHa levels recorded in the short and long term were accompanied by a two fold increase in heart acetyl-CoA concentration and the acetyl-CoA/CoASH ratio. Tissue long-chain acyl-CoA and triacylglycerol levels were also significantly higher in SRD fed rats. Spontaneous normalization of all the above metabolic parameters was observed during the medium term on SRD. Glucose-6-phosphate levels remained within control values during the short and medium term, in contrast to a two fold increase recorded in the long term on SRD. Glycogen concentrations were found moderately elevated only in the long term. Citrate concentrations were slightly increased in the short and greatly in the long term, and the fructose-2,6-bisphosphate/citrate ratio was found significantly decreased only during the long term on SRD. After 3 weeks on SRD, the protal vein Insulin/Glucagon (I/G) molar ratio was three times higher in SRD than STD rats, as opposed to an unchanged I/G ratio found in the long term.(ABSTRACT TRUNCATED AT 250 WORDS)