RESUMO
The aim of this study was to improve insulin sensitivity in fructose-treated animals by ingestion of flavonoid quercetin. Several signs of insulin resistance have been developed in rats by drinking 10% fructose solution for 9 weeks. The effect of 6-week-gavage-administrated quercetin (20 mg/kg/day in 1% methyl cellulose solution) was monitored. Rats of the control groups received methyl cellulose vehicle as well. The most striking result of the quercetin treatment was the normalization of the fructose solution drinking to the level of drinking water intake. In addition, quercetin supplementation considerably decreased the plasma glucose and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index in rats consuming fructose. Surprisingly, fructose ingestion did not elevate plasma uric acid, thiobarbituric acid reactive substances, nitrotyrosine, or advanced glycation end products fluorescence. Instead, a reduction of the above parameters was observed. In summary, these results indicate that quercetin supplementation reduces fructose drinking and decreases plasma glucose and the HOMA-IR index. Furthermore, methyl cellulose, in combination with fructose, causes uric acid - lowering, antioxidant and anti-glycation effects. Thus, methyl cellulose possibly shifts fructose metabolism in favor of the utilization of antioxidant features of fructose. Our results call for using methyl cellulose in sweetened beverages and other sweetened food.
Assuntos
Frutose , Resistência à Insulina , Quercetina , Ratos Wistar , Ácido Úrico , Animais , Frutose/administração & dosagem , Quercetina/farmacologia , Quercetina/administração & dosagem , Ácido Úrico/sangue , Ratos , Masculino , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ingestão de Líquidos/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Glicemia/metabolismo , Glicemia/efeitos dos fármacosRESUMO
Cholecalciferol improves insulin signaling and glucose metabolism in the heart and reduces circulating non-esterified fatty acids. Cholecalciferol effects on the cardiac fatty acid (FA) metabolism and the consequences on calcium handling were examined. Blood lipid profile was determined. Western blot and qRT-PCR were used to examine protein and mRNA expression. Cholecalciferoltreated rats had increased acetyl CoA carboxylase 2 protein expression and decreased expression of malonyl CoA decarboxylase. In addition, the expression of uncoupling protein 3 was elevated. Also, the level of peroxisome proliferator-activated receptor-gamma coactivator in the nucleus of heart cells was increased along with the level of sarcoplasmic/endoplasmic reticulum Ca2+ATPase in the microsomal fraction. In parallel, the L-type calcium channel and ryanodine receptor expression was reduced. In the heart of healthy rats, cholecalciferol affects proteins regulating malonyl CoA availability and intracellular Ca2+ handling proteins.
Assuntos
Cálcio , Malonil Coenzima A , Ratos , Animais , Malonil Coenzima A/metabolismo , Colecalciferol , Ácidos Graxos/metabolismo , CoraçãoRESUMO
Walnut consumption mostly has a positive implication for cardiovascular health. Walnut diet effects on the cardiac fatty acid (FA) metabolism of healthy rats and those with fructose diet-induced metabolic burden were analysed. Both walnuts and fructose increased CD36 transporter level and the nuclear content of some/all of Lipin 1/PPARα/PGC-1 complex partners, as well as cytosolic and nuclear FOXO1. However, fructose, independently of walnuts, increased the content of palmitic (PA), oleic, and vaccenic acid (VA), while in walnut-fed rats failed to increase palmitoleic acid (POA) level and the POA/PA ratio, as well as total MUFA content. In opposite, walnuts reduced the level of PA and VA and increased alpha-linolenic, eicosapentaenoic and docosapentaenoic acid level, regardless of fructose. In conclusion, both fructose and walnuts stimulated the uptake and oxidation of FA in the heart, but the walnuts, opposite to fructose, favourably altered cardiac FA profile in healthy and metabolically compromised rats.
Assuntos
Ácidos Graxos Ômega-3 , Juglans , Ratos , Animais , Ácidos Graxos Ômega-3/farmacologia , Frutose , PPAR alfa , NozesRESUMO
Consumption of walnuts is beneficial for cardiovascular health. To study walnut effects on proteins involved in vascular tone regulation, control and fructose-fed rats were subjected to walnut diet for 6 weeks. In contrast with increased energy intake and body mass gain, aortic protein level of L-type calcium channel alpha subunit was decreased and the level of SUR2B subunit of ATP-sensitive K + channel was increased in healthy rats subjected to walnuts, together with improved Akt phosphorylation. Upon the walnut diet in rats subjected to fructose overload, the rise in energy intake and body mass gain, was followed by an increase in blood insulin. Although SUR2B level was elevated, the level of sodium-calcium exchanger NCX1 and inducible nitric oxide synthase were reduced and increased, respectively. In summary, walnut consumption was accompanied with moderate beneficial vascular effect in healthy rats, while an effect of walnut in rats with metabolic disturbances was rather controversial.
Assuntos
Canais de Cálcio/metabolismo , Dieta , Juglans , Canais KATP/metabolismo , Nozes , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Ingestão de Energia , Frutose , Juglans/química , Masculino , Óxido Nítrico , Nozes/química , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Trocador de Sódio e Cálcio/metabolismoRESUMO
Fatty acid (FA) uptake and/or intramuscular triglyceride (TG) accumulation in skeletal muscle are increased in obesity, type 2 diabetes and aging. FA translocase (FAT/CD36) translocation, lipin-1 subcellular localization and nuclear factor kappa B (NF-κB) p65 protein content in quadriceps muscle of young and old obese Zucker fa/fa rats and their lean controls were analyzed by immunoblot to define obesity- and aging-related alterations in FA uptake, their subsequent metabolic fate and potential to activate pro-inflammatory signaling. As expected, obesity increased FAT/CD36 content in plasma membrane in quadriceps muscle of fa/fa rats. Aging increased cytosolic lipin-1 content in both, obese rats and their lean controls. Also, old obese rats had decreased level of nuclear extract lipin-1compared to that in old lean rats. Neither obesity nor age altered NF-κB p65 protein content in cytosol and nuclear extract of quadriceps muscle suggesting that obesity/aging-induced changes in FA handling are not accompanied by NF-κB-mediated inflammation. Increase in plasma membrane FAT/CD36 content in obese rats and failure in lipin-1 export to nucleus with progression of obesity, implying an increase in FA uptake and their different channeling into lipid intermediates synthesis pathway in old fa/fa rats versus FA usage in lean rats of the same age.
Assuntos
Envelhecimento/metabolismo , Antígenos CD36/metabolismo , Caderinas/metabolismo , Músculo Esquelético/metabolismo , Proteínas Nucleares/metabolismo , Obesidade/metabolismo , Frações Subcelulares/metabolismo , Animais , Masculino , Transporte Proteico , Ratos , Ratos ZuckerRESUMO
Fructose-rich diets (FRD) cause cardiac insulin resistance manifested by impairment of Akt/endothelial NO synthase (eNOS) signalling. In contrast, oestradiol (E2) activates this signalling pathway in the heart. To study the ability of E2 to revert the detrimental effect of fructose on cardiac Akt/eNOS, female rats were subjected to a FRD and ovariectomy followed with or without E2 replacement. We also analysed the effects of the FRD and E2 on cardiac extracellular signal-regulated kinase (Erk 1/2) signalling related to their role in cardiac hypertrophy development. Expression of Akt, eNOS and Erk 1/2, as well as regulatory phosphorylations of these molecules were determined. The protein expression of cardiac Akt and eNOS was not affected by the diet or E2 treatment. However, the FRD was accompanied by a decrease in Akt phosphorylation at Ser(473) and Thr(308), and eNOS at Ser(1177), while the phosphorylation of eNOS at Thr(495) was increased. E2 replacement in ovariectomised fructose-fed rats caused a reversion of the diet effect on Akt and eNOS serine phosphorylation, but mostly had no effect on threonine phosphorylation of the molecules. The FRD and E2 treatment did not influence Erk 1/2 expression and phosphorylation and heart mass as well. The data show that E2 selectively suppress the negative effects of a FRD on Akt/eNOS signalling and probably point to the different effects of E2 on kinase/phosphatase pathways responsible for phosphorylation/dephosphorylation of Akt and eNOS. Furthermore, the results suggest that the heart of females in the reproductive period is partially protected against the damaging effects of increasedfructose intake.
Assuntos
Carboidratos da Dieta/efeitos adversos , Estradiol/farmacologia , Frutose/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Carboidratos da Dieta/administração & dosagem , Estradiol/administração & dosagem , Estradiol/metabolismo , Feminino , Frutose/administração & dosagem , Frutose/efeitos adversos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Coração/fisiologia , Resistência à Insulina , Óxido Nítrico Sintase Tipo III/genética , Ovariectomia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacosRESUMO
CONTEXT: Excessive fructose consumption causes ectopic lipid storage leading to metabolic disorders and cardiovascular diseases associated with defective substrate utilisation in the heart. OBJECTIVE: Examining the preventive impact of low-intensity exercise on alterations related to fructose-rich diet (FRD) on cardiac fatty acid (FA) transport and metabolism. MATERIALS AND METHODS: Male Wistar rats were divided into control and two groups that received 10% fructose for 9 weeks, one of which was additionally exposed to exercise. RESULTS: FRD elevated plasma and cardiac TAG, FATP1 in plasma membrane, Lipin 1 in microsomes and HSL mRNA, while mitochondrial CPT1 was decreased. Exercise decreased plasma free FA level, raised CD36 in plasma membrane and FATP1 in lysate, mitochondrial CPT1 and decreased microsomal Lipin 1 in fructose-fed rats. CONCLUSIONS: FRD changed plasma lipids and augmented partitioning of FA to TAG storage in the heart, whereas exercise in FRD rats switched metabolism of FA towards ß-oxidation.
Assuntos
Frutose , Metabolismo dos Lipídeos , Ratos , Masculino , Animais , Ratos Wistar , Ácidos Graxos/metabolismo , Triglicerídeos/metabolismoRESUMO
Background and Aim: Excessive fructose consumption along with a sedentary lifestyle provokes metabolic disorders and cardiovascular diseases. Fructose overload causes cardiac insulin resistance and increases reliance on fatty acid (FA) uptake and catabolism. The cardiometabolic benefits of exercise training have long been appreciated. The goal of the presented study is to shed a new light to the preventive role of exercise training on cardiac lipid metabolism in fructose-fed rats. Methods: Male Wistar rats were divided into control (C), sedentary fructose (F), and exercised fructose (EF) groups. Fructose was given as a 10% fructose solution in drinking water for 9 weeks. Low-intensity exercise training was applied for 9 weeks. The protein expression and subcellular localization of Lipin1, peroxisome proliferator-activated receptor α (PPARα), and peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC1) were analyzed in the heart using Western blot. Cardiac forkhead box transcription factor 1 (FOXO1) and sirtuin 1 (SIRT1) protein levels were also evaluated. Gene expression of long-chain acyl-CoA dehydrogenase was analyzed by quantitative polymerase chain reaction. Results: Exercise training has augmented the expression of main regulators of FA oxidation in the heart and achieves its effect by increasing the nuclear content of PPARα, Lipin1, and FOXO1 compared with the fructose group (P = 0.0422, P = 0.000045, P = 0.00958, respectively). In addition, Lipin1, FOXO1, and SIRT1 were increased in nuclear extract after exercise compared with the control group (P = 0.000043, P = 0.0417, P = 0.0329, respectively). In cardiac lysate, low-intensity exercise caused significantly increased protein level of PPARα, PGC1, FOXO1, and SIRT1 compared with control (P = 0.0377, P = 0.0275, P = 0.0096, P = 0.0282, respectively) and PGC1 level compared with the fructose group (P = 0.0417). Conclusion: The obtained results imply that the heart with a metabolic burden additionally relies on FA as an energy substrate after low-intensity running.
Assuntos
Exercício Físico , Proteína Forkhead Box O1 , Metabolismo dos Lipídeos , PPAR alfa , Animais , Masculino , Ratos , Exercício Físico/fisiologia , Ácidos Graxos/metabolismo , Proteína Forkhead Box O1/metabolismo , Frutose/efeitos adversos , Frutose/metabolismo , Metabolismo dos Lipídeos/genética , PPAR alfa/genética , PPAR alfa/metabolismo , Ratos Wistar , Sirtuína 1/genéticaRESUMO
The transport of cations in the cardiomyocytes, crucial for the functioning of the heart, can be affected by walnut diet due to the high content of polyunsaturated fatty acids. Healthy and metabolically compromised rats (drinking 10% fructose solution) were subjected to a diet supplemented with 2.4 g of walnuts for 6 weeks to investigate the effect on proteins involved in cation transport in the heart cells. Fructose increased the level of the α1 subunit of Na+/K+-ATPase and the phosphorylation of extracellular signal-regulated kinase 1/2 in the heart of control and walnut-eating rats, while elevated L-type calcium channel α (LTCCα), sodium-calcium exchanger 1 (NCX1), and Maxi Kα level were observed only in rats that did not consume walnuts. However, walnuts significantly increased the cardiac content of LTCC, NCX1, and Maxi Kα, as well as Kir6.1 and SUR2B subunits of KATP channel, but only in fructose-naive rats. In animals that drank fructose, a significant increasing effect of walnuts was observed only in Akt kinase phosphorylation, which may be a part of the antiarrhythmic mechanism of decreasing cation currents in cardiomyocytes. The walnut diet-induced increase in LTCC and NCX1 expression in healthy rats may indicate intense cardiac calcium turnover, whereas the effect on Kir6.1 and SUR2B subunits suggests stimulation of KATP channel transport in the cardiac vasculature. The effects of walnuts on the cation-handling proteins in the heart, mostly limited to healthy animals, suggest the possible use of a walnut-supplemented diet in the prevention rather than the treatment of cardiological channelopathies.
Assuntos
Juglans , Ratos , Masculino , Animais , Dieta , Cátions , Frutose , Trifosfato de AdenosinaRESUMO
A number of alterations have been identified in lipid metabolism within adipose tissue and liver in obesity. Less is known about the capacity of skeletal muscle for the metabolism of fatty acids in obesity-related insulin resistance, though it is evident that dry cow muscles may contain increased triglyceride content. The current study was therefore undertaken to evaluate the skeletal muscle expression of proteins of the fatty acid metabolism in dry cows with different body condition scores (BCS). Sixteen Holstein-Friesian close-up cows were divided into 2 equal groups based on their BCS as optimal (3.25 ≤ BCS ≤ 3.5) and high (4.0 ≤ BCS ≤ 4.25). Blood samples collection and skeletal muscle biopsies were carried out at day 10 before calving. Blood serum was assayed for concentration of resistin using a bovine specific ELISA. Protein expression of insulin receptor beta subunit (IRß), glucose transporter 4 (GLUT4), fatty acid translocase (FAT/CD36), fatty acid transporter 1 (FATP1), carnitine palmitoyltransferase 1 (CPT1), AMP-acitvated protein kinase (AMPK) and lipin 1 were analyzed in semitendinosus muscle by immunoblot. Resistin differed non-significantly between high-BCS and optimal-BCS cows. Insulin-resistant lipid metabolism in obese cows was paralleled with increased skeletal muscle expression of lipin 1 and GLUT4, and decreased expression of IRß and FATP1. These data suggest that in obesity-related insulin resistance, metabolic capacity in dry cow skeletal muscles appears to be organized towards the synthesis of signaling intermediates rather than fatty acids oxidation and that altered fatty acid uptake does not contribute to this disposition.
Assuntos
Doenças dos Bovinos , Resistência à Insulina , Animais , Antígenos CD36/metabolismo , Bovinos , Doenças dos Bovinos/metabolismo , Ácidos Graxos/metabolismo , Feminino , Insulina , Resistência à Insulina/fisiologia , Lactação/fisiologia , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Obesidade/veterinária , Compostos Orgânicos , Resistina/metabolismoRESUMO
Increased fructose consumption has been linked with chronic inflammation and metabolic syndrome (MetS). Activation of the renin-angiotensin system (RAS) and NF-κB have been detected in MetS. Walnuts are a rich source of polyunsaturated omega-3 fatty acids (n-3 PUFA) that were suggested to exert anti-inflammatory effects related to cardio-metabolic health. We hypothesized that walnut supplementation has the capacity to revert unfavorable fructose-rich diet (FRD)-induced activation of cardiac RAS and NF-κB in male rats. Due to the lack of similar studies, we investigated the effects of walnut supplementation (6 weeks) on the expression of four RAS molecules (ACE, ACE2, AT1R, and AT2R) and NF-κB in rat heart after FRD (10% w/v, 9 weeks). In addition, we followed the changes in the n-6/n-3 PUFA ratio in the total pool of heart lipids after both treatments to elucidate the walnut effects on fatty acids in the heart. 36 animals (9 per group) participated in the experiment. FRD significantly increased the ACE protein level in the heart (p < 0.001). Walnut supplementation significantly increased the ACE2 protein level in the heart of FRD (p < 0.001). In addition, walnut supplementation showed a significant main effect on the arachidonic acid/eicosapentaenoic acid ratio (p = 0.004). Walnut supplementation significantly reduced this ratio, in comparison with both, the control group (C vs. FW, p < 0.05) and the FRD group (F vs. FW, p < 0.05). However, walnut treatment failed to revert the significant effect of fructose (p < 0.001) on the elevation of NF-κB protein level. Our results suggest a beneficial effect of walnut supplementation on ACE2 protein level and n-6/n-3 PUFA level in the heart of the animal model of MetS. Such results highlight the approach of omega-3-rich walnut supplementation in the stimulation of endogenous production of favorable molecules in the heart which could be an affordable nutritional treatment formaintenance of cardio-metabolic health.
RESUMO
BACKGROUND: Fructose consumption produces deleterious metabolic effects in animal models. The sites of fructose-induced insulin resistance are documented to be the liver, skeletal muscle, and adipose tissue, but effects of fructose-rich diet on cardiac insulin signaling and action were not investigated. PURPOSE AND METHODS: In order to study the potential fructose effects on development of cardiac insulin resistance, we analyzed biochemical parameters relevant for insulin action and phosphorylation of insulin signaling molecules, plasma membrane glucose transporter type 4 (GLUT4) content, and phosphorylation of endothelial nitric oxide synthase (eNOS), in ovariectomized female rats on fructose-enriched diet, in basal and insulin-stimulated conditions. RESULTS: Fructose-fed rats (FFR) had increased content of visceral adipose tissue, but not body weight. Food intake was decreased, while fluid and caloric intake were increased in FFR. Additionally, fructose diet increased plasma insulin, blood triglycerides level, and HOMA index. Stimulation of protein kinase B (Akt) signaling pathway by insulin was reduced in rats on fructose-enriched diet, but effect of fructose on extracellular signal-regulated kinase (Erk 1/2) phosphorylation was not observed. Furthermore, insulin-induced GLUT4 presence in plasma membranes of cardiac cells was decreased by fructose diet, as well as insulin stimulation of eNOS phosphorylation at Ser(1177). CONCLUSION: In summary, these results strongly support our hypothesis that fructose diet-induced changes of plasma lipid profile and insulin sensitivity are accompanied with decrease in cardiac insulin action in ovariectomized female rats.
Assuntos
Frutose/administração & dosagem , Coração/efeitos dos fármacos , Insulina/sangue , Ovariectomia , Transdução de Sinais/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Animais , Western Blotting , Eletroforese em Gel de Poliacrilamida , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Transportador de Glucose Tipo 4/sangue , Resistência à Insulina , Fígado/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/sangueRESUMO
The benefits of walnut (Juglans regia) consumption for metabolic health are known, but the molecular background underlying their putative antioxidant and anti-inflammatory/immunomodulatory effects is underexplored. We assessed that walnut supplementation (6 weeks) reverted unfavorable changes of the SIRT1/FoxO3a/MnSOD/catalase axis in the heart induced by fructose-rich diet (FRD). Intriguingly, Nox4 was increased by both FRD and walnut supplementation. FRD increased the cytosolic fraction and decreased the nuclear fraction of the uniquely elucidated ChREBP in the heart. The ChREBP nuclear fraction was decreased in control rats subjected to walnuts. In addition, walnut consumption was associated with a reduction in systolic BP in FRD and a decrease in fatty acid AA/EPA and AA/DHA ratios in plasma. In summary, the protective effect of walnut supplementation was detected in male rats following the fructose-induced decrease in antioxidative/anti-inflammatory capacity of cardiac tissue and increase in plasma predictors of low-grade inflammation. The current results provide a novel insight into the relationship between nutrients, cellular energy homeostasis, and the modulators of inflammatory/immune response in metabolic syndrome, emphasizing the heart and highlighting a track for translation into nutrition and dietary therapeutic approaches against metabolic disease.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Catalase/efeitos dos fármacos , Suplementos Nutricionais/análise , Ácidos Graxos/sangue , Frutose/efeitos adversos , Coração/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Juglans/química , Sirtuína 1/efeitos dos fármacos , Animais , Anti-Inflamatórios , Humanos , Ratos , Ratos WistarRESUMO
CONTEXT: The evidence on potential cross-talk of vitamin D and insulin in the regulation of cardiac metabolism is very scanty. OBJECTIVE: Cholecalciferol was administered to male Wistar rats for six weeks to study its effects on cardiac glucose metabolism regulation. MATERIALS AND METHODS: An expression, phosphorylation and/or subcellular localisation of insulin signalling molecules, glucose transport and metabolism key proteins were studied. RESULTS: Circulating non-esterified fatty acids (NEFA) level was lower after cholecalciferol administration. Cholecalciferol decreased cardiac insulin receptor substrate 1 Ser307 phosphorylation, while insulin-stimulated Akt Thr308 phosphorylation was increased. Cardiac 6-phosphofructo-2-kinase protein, hexokinase 2 mRNA level and insulin-stimulated glycogen synthase kinase 3ß Ser9 phosphorylation were also increased. Finally, FOXO1 transcription factor cytosolic level was reduced. CONCLUSION: Vitamin D-related improvement of insulin signalling and insulin regulation of glucose metabolism in the rat heart is accompanied by the decrease of blood NEFA level and dysregulation of cardiac FOXO1 signalling.
RESUMO
We previously reported that low-intensity exercise prevented cardiac insulin resistance induced by a fructose-rich diet (FRD). To examine whether low-intensity exercise could prevent the disturbances of key molecules of cardiac glucose metabolism induced by FRD in male and ovariectomized (ovx) female rats, animals were exposed to 10% fructose solution (SF) or underwent both fructose diet and exercise (EF). Exercise prevented a decrease in cardiac GSK-3ß phosphorylation induced by FRD in males (p < .001 vs. SF). It also prevented a decrease in PFK-2 phosphorylation in ovx females (p < .001 vs. SF) and increased the expression of PFK-2 in males (p < .05 vs. control). Exercise did not prevent a decrease in plasma membrane GLUT1 and GLUT4 levels in ovx females on FRD. The only effect of exercise on glucose transporters that could be indicated as beneficial is an augmented GLUT4 protein expression in males (p < .05 vs. control). Obtained results suggest that low-intensity exercise prevents harmful effects of FRD towards cardiac glycogenesis in males and glycolysis in ovx females. PRACTICAL APPLICATIONS: Low-intensity exercise, equivalent to brisk walking, was able to prevent disturbances in cardiac glycolysis regulation in ovx female and the glycogen synthesis pathway in male rats. In terms of human health, although molecular mechanisms of beneficial effects of exercise on cardiac glucose metabolism vary between genders, low-intensity running may be a useful non-pharmacological approach in the prevention of cardiac metabolic disorders in both men and postmenopausal women.
Assuntos
Frutose , Coração , Animais , Dieta , Feminino , Frutose/efeitos adversos , Glicogênio Sintase Quinase 3 beta , Glicólise , Masculino , RatosRESUMO
Both a diet rich in fructose and chronic stress exposure induce metabolic and cardiovascular disturbances. The aim of this study was to examine the effects of the fructose-rich diet and chronic stress, separately and in combination, on insulin signaling and molecules regulating glycogen synthesis and ion transport in the heart, and to reveal whether these effects coincide with changes in glucocorticoid receptor (GR) activation. Male Wistar rats were subjected to 10% fructose in drinking water and/or to chronic unpredictable stress for 9 weeks. Protein expression and/or phosphorylation of the insulin receptor (IR), protein tyrosine phosphatase 1B, insulin receptor substrate 1 (IRS1), protein kinase B (Akt), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase-3ß (GSK-3ß) and Na+/K+-ATPase α-subunits in cardiac tissue were analyzed by western blot. GR distribution between cytosolic and nuclear fractions was also analyzed. The fructose-rich diet decreased the level of pERK1/2 (Thr202/Tyr204) and pGSK-3ß (Ser9) independently of stress, while chronic stress increased the IRS1 content and prevented the fructose diet-induced decrease of the pAkt (Ser473) level. The fructose-rich diet in combination with chronic stress reduced the protein content of cardiac IR and attenuated IRS1 upregulation. Separate treatments increased the protein content of Na+/K+-ATPase α1- and α2-subunits, while after combined treatment the α2 content was at the control level and the α1 content was lower than the control level. The effect of combined treatment on cardiac IR and α2-subunit expression could be mediated by increased GR nuclear accumulation. Our study provides new insights into the effects of chronic stress and a combination of the fructose diet and chronic stress on the studied molecules in the heart.
Assuntos
Frutose/farmacologia , Glicogênio Sintase Quinase 3 beta/efeitos dos fármacos , Coração/efeitos dos fármacos , Receptor de Insulina/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , Animais , Dieta , Glicogênio Sintase Quinase 3 beta/metabolismo , Masculino , Ratos , Ratos Wistar , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Estresse FisiológicoRESUMO
Increased dietary, blood, and tissue n-6/n-3 fatty acid ratios are associated with obesity and metabolic syndrome. Due to Westernized dietary patterns, the increasing n-6/n-3 ratio is of growing concern worldwide, and dietary strategies aimed at its lowering are of public health importance. Walnuts are rich in dietary fats, and their consumption promotes cardiometabolic health. This study aimed to examine the effect of 6-week walnut consumption on tissue-specific n-6/n-3 ratio and fatty acid metabolic conversion in fructose-fed rats with a cluster of metabolic disorders. Male Wistar rats were fed a standard diet with or without 10% fructose in drinking water for 9 weeks. Diets of half of the animals were then supplemented with walnuts (2.4 g/day) for 6 weeks, upon which fatty acid profiles were determined in plasma, liver, adipose tissue, and kidney total lipids. Results showed that walnuts induced significant decreases in the n-6/n-3 content of total lipid pool in plasma and examined tissues, irrespective of metabolic burden. Walnut intervention decreased plasma and liver palmitoleic/palmitic, arachidonic/linoleic, and docosahexaenoic/α-linolenic acid ratios. It also modulated individual fatty acid levels by reducing arachidonic and palmitic acid and increasing α-linolenic, eicosapentaenoic, and docosapentaenoic acid in plasma and most tissues. Our study demonstrated that 6-week consumption of walnuts favorably modulated n-6/n-3 plasma and tissue ratio in male Wistar rats regardless of high-fructose feeding, underscoring the promising potential of walnuts in both prevention and treatment of the metabolic syndrome.
RESUMO
It is well known that variation in the concentration of estrogens affects insulin action. In this study we examine the impact of estradiol (E2) on insulin signaling in the rat heart. Ovariectomized female rats were treated with E2 6 h prior to analysis of basal protein and mRNA content of insulin signaling molecules, and additionally with insulin 30 min before the experiment to delineate E2 effects on phosphorylations and molecular associations relevant for insulin signaling. The results show that E2 decreased insulin receptor (IR) tyrosine phosphorylation, while it did not alter IR protein and mRNA content. E2 administration did not change IR substrate 1 (IRS-1) protein content and tyrosine phosphorylation, while decreased mRNA content and increased its association with the p85 subunit of phosphatidylinositol 3-kinase (PI3K). E2 decreased protein and mRNA content of IR substrate 2 (IRS-2), while did not change IRS-2 tyrosine phosphorylation and IRS-2 association with p85. The increase of IRS-1/p85 is accompanied by increase of p85 protein and mRNA levels, and by stimulation of protein kinase B (Akt) Ser(473) phosphorylation. In contrast, Akt protein and mRNA content were not changed. In summary, although in some aspects cardiac insulin signaling is obviously improved by E2 treatment (increase of p85 mRNA and protein levels, enhancement of IRS-1/p85 association and Ser(473)Akt phosphorylation), the observed decrease of IR tyrosine phosphorylation, IRS-2 protein content, and IRSs mRNA contents, suggest very complex interplay of beneficial and suppressive effects of E2, both genomic and non-genomic, in regulation of heart insulin signaling.
Assuntos
Estradiol/farmacologia , Coração/efeitos dos fármacos , Insulina/metabolismo , Miocárdio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Glicemia/metabolismo , Ácidos Graxos não Esterificados/sangue , Feminino , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Ovariectomia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Transdução de Sinais/fisiologia , SuínosRESUMO
Exercise is important nonpharmacological treatment for improvement of insulin sensitivity in menopause. However, its effect on menopausal cardiac insulin resistance is needing further research. We investigated protective effects of low-intensity exercise on cardiac insulin signaling, inflammation, regulation of nitric oxide synthase (NOS) and matrix metalloproteinase 9 (MMP-9) in ovariectomized (OVX) Wistar rats, submitted to 10% fructose solution for 9 weeks. OVX rats were divided into control, sedentary fructose, and exercise fructose groups. Measurements of physical and biochemical characteristics were carried out to evaluate metabolic syndrome development. Messenger RNA and protein levels and phosphorylation of cardiac insulin signaling molecules, endothelial and inducible NOS (eNOS and iNOS), p65 subunit of nuclear factor κB (NFκB), tumor necrosis factor α (TNF-α), suppressor of cytokine signaling 3 (SOCS3), and MMP-9 were analyzed. Fructose increased insulin level, homeostasis model assessment (HOMA) index, and visceral adipose tissue weight, while low-intensity exercise prevented insulin level and HOMA index increase. Fructose also decreased cardiac pAkt (Ser473), peNOS (Ser1177) and increased insulin receptor substrate 1 (IRS1) phosphorylation at Ser307, pNFκB (Ser276) and NFκB and MMP-9 content, without any effect on iNOS, protein-tyrosine phosphatase 1B, TNF-α, and SOCS3. Exercise prevented changes in pIRS1 (Ser307), pAkt (Ser473), peNOS (Ser1177), pNFκB (Ser276), and NFκB expression. In addition, exercise increased pIRS1 (Tyr632), pAkt (Thr308), and eNOS expression. Low-intensity exercise prevented cardiac insulin signaling disarrangement in fructose-fed OVX rats and therefore eNOS dysfunction, as well as pro-inflammatory signaling activation, without effect on tissue remodeling, suggesting physical training as a way to reduce cardiovascular risk.
Assuntos
Frutose/efeitos adversos , Coração/fisiopatologia , Inflamação/prevenção & controle , Resistência à Insulina , Condicionamento Físico Animal , Transdução de Sinais , Animais , Feminino , Metaloproteinase 9 da Matriz/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ovariectomia , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Ratos , Ratos Wistar , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Insulin-like growth factor-1 (IGF-1) is a hormone and growth factor closely related to insulin. The autocrine/paracrine actions of IGF-1 involve activation of inducible nitric oxide synthase (iNOS) and the Na(+), K(+)-ATPase sodium pump in cardiovascular tissues. Data from literature indicate that iNOS is expressed in vascular smooth muscle cells (VSMC) and that IGF-1-induced release of NO is both rapid and delayed. We hypothesize that impaired IGF-1-induced sodium pump activity/expression in rats with type 1 diabetes is related to activation of phosphatidylinositol 3 kinase (PI3K)/cytosolic phospholipase 2 (cPLA(2))/protein kinase B (Akt) signaling, and that IGF-1 prevents acute and chronic dysfunction of iNOS and sodium pump activity in a chemically induced model of type 1 diabetes, the streptozotocin-treated rat heart (STZ). Understanding how iNOS and sodium pump activity are regulated by IGF-1 activation of the PI3K/cPLA(2)/Akt cascade should provide novel and fundamental knowledge regarding the regulatory actions of IGF-1 in promoting vasodilation. Since insulin resistance is currently a major focus of research, the use of IGF-1 to improve insulin resistance and glucose metabolism has opened a new arena for treatment of comorbid conditions. Future investigations should now focus on mechanisms of action of IGF-1 and its clinical applicability.