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1.
Sci Rep ; 9(1): 11443, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391506

RESUMO

Obstructive sleep apnea syndrome (OSA) promotes aortic dilatation, increased stiffness and accelerated atherosclerosis, but the mechanisms of vascular remodelling are not known. We aimed to assess vascular remodelling, its mechanisms, and the effect of mesenchymal stem cells (MSC) infusions in a clinically relevant rat model of chronic OSA involving recurrent airway obstructions leading thoracic pressure swings and intermittent hypoxia/hypercapnia (OSA-rats). Another group of rats were placed in the same setup without air obstructions (Sham-rats) and were considered controls. Our study demonstrates that chronic, non-invasive repetitive airway obstructions mimicking OSA promote remarkable structural changes of the descending thoracic aorta such as eccentric aortic hypertrophy due to an increased wall thickness and lumen diameter, an increase in the number of elastin fibers which, in contrast, get ruptured, but no changes in tunica media fibrosis. As putative molecular mechanisms of the OSA-induced vascular changes we identified an increase in reactive oxygen species and renin-angiotensin system markers and an imbalance in oxide nitric synthesis. Our results also indicate that MSC infusion blunts the OSA-related vascular changes, most probably due to their anti-inflammatory properties.

2.
PLoS One ; 14(6): e0217926, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31181097

RESUMO

BACKGROUND: AXL is a receptor tyrosine kinase that has been related to kidney and vascular disorders. Heart failure patients with reduced ejection fraction have higher AXL in serum than controls. No information about Axl expression with HF progression is available. METHODS: Thoracic transverse aortic constriction (TAC) was successfully performed on male Wistar rats (n = 25) with different constriction levels. Controls underwent sham surgery (n = 12). Echocardiography measurements were performed 4-8 weeks after surgery. Collagen deposition was measured with picrosirius red staining. Axl mRNA levels in left ventricle (LV), left kidney (LK) and ascending aorta (aAo) and the LV expression of cardiac remodeling and fibrogenic factors were quantified with real-time PCR. AXL LV protein levels were quantified with western blot and localization was analyzed by immunohistochemistry. Soluble AXL levels in plasma were assayed with ELISA. RESULTS: Successful TAC rats were classified into LV hypertrophy (LVH) or heart failure (HF), modeling the progressive cardiac changes after pressure overload. Collagen deposition was increased only in the HF group. LV Axl mRNA levels were higher in LVH and HF than in Sham rats, and correlated with LVHi, and hypertrophic and fibrogenic mediators. However, no association was found with LV systolic function. AXL was expressed in LV myocytes and other cell types. Concentration of circulating sAXL in plasma was increased in the LVH group compared to Sham and HF rats. Axl mRNA levels were similar in all groups in the LK and aAo. CONCLUSIONS: Axl expression pattern suggests a role in the early progression of LV remodeling in HF but not in the later systolic dysfunction. The higher levels of circulating AXL found in HF patients most probably shed from the heart.


Assuntos
Insuficiência Cardíaca/sangue , Receptores Proteína Tirosina Quinases/metabolismo , Remodelação Ventricular , Animais , Pressão Sanguínea , Progressão da Doença , Ecocardiografia , Hipertrofia Ventricular Esquerda , Masculino , Ratos , Ratos Wistar , Receptores Proteína Tirosina Quinases/sangue
3.
Int J Mol Sci ; 20(5)2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30841536

RESUMO

One of the most important threats to global human health is the increasing incidences of metabolic pathologies (including obesity, type 2 diabetes and non-alcoholic fatty liver disease), which is paralleled by increasing consumptions of hypercaloric diets enriched in simple sugars. The challenge is to identify the metabolic pathways affected by the excessive consumption of these dietary components when they are consumed in excess, to unravel the molecular mechanisms leading to metabolic pathologies and identify novel therapeutic targets to manage them. Mechanistic (mammalian) target of rapamycin (mTOR) has emerged as one of the key molecular nodes that integrate extracellular signals, such as energy status and nutrient availability, to trigger cell responses that could lead to the above-mentioned diseases through the regulation of lipid and glucose metabolism. By activating mTOR signalling, excessive consumption of simple sugars (such as fructose and glucose), could modulate hepatic gluconeogenesis, lipogenesis and fatty acid uptake and catabolism and thus lipid deposition in the liver. In the present review we will discuss some of the most recent studies showing the central role of mTOR in the metabolic effects of excessive simple sugar consumption.


Assuntos
Frutose/metabolismo , Glucose/metabolismo , Fígado/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Humanos , Metabolismo dos Lipídeos , Transdução de Sinais
4.
Eur J Nutr ; 58(3): 1283-1297, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29516226

RESUMO

PURPOSE: Sugar-sweetened beverage intake is a risk factor for insulin resistance, dyslipidemia, fatty liver, and steatohepatitis (NASH). Sub-chronic supplementation of liquid fructose, but not glucose, in female rats increases liver and plasma triglycerides without inflammation. We hypothesized that chronic supplementation of fructose would cause NASH and liver insulin resistance. METHODS: We supplemented female Sprague-Dawley rats with water or either fructose or glucose 10% w/v solutions under isocaloric conditions for 7 months. At the end, plasma analytes, insulin, and adiponectin were determined, as well as liver triglyceride content and the expression of key genes controlling inflammation, fatty acid synthesis and oxidation, endoplasmic reticulum stress, and plasma VLDL clearance, by biochemical and histological methods. RESULTS: Although sugar-supplemented rats increased their energy intake by 50-60%, we found no manifestation of liver steatosis, fibrosis or necrosis, unchanged plasma or tissue markers of inflammation or fibrosis, and reduced liver expression of gluconeogenic enzymes, despite both sugars increased fatty acid synthesis, mTORC1, and IRE1 activity, while decreasing fatty acid oxidation and PPARα activity. Only fructose-supplemented rats were hypertriglyceridemic, showing a reduced expression of VLDL receptor and lipoprotein lipase in skeletal muscle and vWAT. Glucose-supplemented rats showed increased adiponectinemia, which would explain the different metabolic outcomes of the two sugars. CONCLUSIONS: Chronic liquid simple sugar supplementation, as the sole risk factor, is not enough for female rats to develop NASH and increased liver gluconeogenesis. Nevertheless, under isocaloric conditions, only fructose induced hypertriglyceridemia, thus confirming that also the type of nutrient matters in the development of metabolic diseases.


Assuntos
Fígado Gorduroso , Frutose/administração & dosagem , Frutose/efeitos adversos , Hipertrigliceridemia/induzido quimicamente , Inflamação , Receptores de LDL/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
5.
Mol Nutr Food Res ; 62(22): e1800777, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30260587

RESUMO

SCOPE: The effect of chronic supplementation with simple-sugar solutions on leptin signaling in liver, hypothalamus, and visceral white adipose tissue (vWAT) is studied, which is designed to mimic the temporal pattern of consumption by humans. METHODS AND RESULTS: Solutions of fructose or glucose are isocalorically supplemented (7 months) in female Sprague-Dawley rats consuming ad libitum rodent chow. After sacrifice, plasma and tissue samples (liver, hypothalamus, and vWAT) are collected. Zoometric parameters, plasma analytes, and the tissue expression and activity of markers of leptin signaling are determined by biochemical and molecular biological methods. The two sugars cause different types of adiposopathy. Both sugars induce increases in plasma nonesterified fatty acids, and leptin resistance in the liver and the hypothalamus. Only fructose-supplemented rats show hyperleptinemia, and increased body weight due to a hypertrophy of vWAT, with no signs of leptin-mediated lipolysis. Glucose-supplemented rats show no significant changes in these parameters but present elevated plasma adiponectin concentrations, lipolysis, and inflammatory markers in vWAT, indicating a shift to a nonexpandable adipose tissue phenotype. CONCLUSION: Chronic consumption of fructose places a greater burden on metabolic homeostasis than equivalent consumption of glucose, inducing hyperleptinemia, generalized leptin resistance, and increased body weight due to expanded, hypertrophic vWAT.


Assuntos
Tecido Adiposo Branco/efeitos dos fármacos , Frutose/efeitos adversos , Glucose/efeitos adversos , Leptina/sangue , Adipócitos/patologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Proteína Relacionada com Agouti/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ratos Sprague-Dawley , Receptores para Leptina/metabolismo
6.
J Nutr Biochem ; 57: 136-144, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29727795

RESUMO

We have recently shown that type of supplemented simple sugar, not merely calorie intake, determines adverse effects on metabolism and aortic endothelial function in female rats. The aim of the current study was to investigate and compare the effects of high consumption of glucose or fructose on mesenteric arterial reactivity and systolic blood pressure (SBP). Sprague-Dawley female rats were supplemented with 20% w/v glucose or fructose in drinking water for 8 weeks. Here, we show that both sugars alter insulin signaling in mesenteric arteries (MA), assessed by a reduction in phosphorylated Akt, and increase in SBP. Furthermore, ingestion of glucose or fructose enhances inducible nitric oxide synthase (iNOS) expression and contractile responses to endothelin and phenylephrine in MA of rats. The endothelium-dependent vasodilation to acetylcholine and bradykinin as well as the relaxation responses to the nitric oxide donor sodium nitroprusside are impaired in MA of fructose- but not glucose-supplemented rats. In contrast, only glucose supplementation increases the expression of phosphorylated endothelial NOS (eNOS) in MA of rats. In conclusion, this study reveals that supplementation with fructose or glucose in liquid form enhances vasocontractile responses and increases iNOS expression in MA, effects which are accompanied by increased SBP in those groups. On the other hand, the preserved vasodilatory responses in MA from glucose-supplemented rats could be attributed to the enhanced level of phosphorylated eNOS expression in this group.


Assuntos
Frutose/efeitos adversos , Glucose/efeitos adversos , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Acetilcolina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Bradicinina/farmacologia , Feminino , Insulina/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos
7.
Mol Neurobiol ; 55(8): 6984-6999, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29372547

RESUMO

Excessive sugar intake has been related to cognitive alterations, but it remains unclear whether these effects are related exclusively to increased energy intake, and the molecular mechanisms involved are not fully understood. We supplemented Sprague-Dawley female rats with 10% w/v fructose in drinking water or with isocaloric glucose solution for 7 months. Cognitive function was assessed through the Morris water maze (MWM) and the novel object recognition (NOR) tests. Plasma parameters and protein/mRNA expression in the frontal cortex and hippocampus were determined. Results showed that only fructose-supplemented rats displayed postprandial and fasting hypertriglyceridemia (1.4 and 1.9-fold, p < 0.05) and a significant reduction in the discrimination index in the NOR test, whereas the results of the MWM test showed no differences between groups. Fructose-drinking rats displayed an abnormal glucose tolerance test and impaired insulin signaling in the frontal cortex, as revealed by significant reductions in insulin receptor substrate-2 protein levels (0.77-fold, p < 0.05) and Akt phosphorylation (0.72-fold, p < 0.05), and increased insulin-degrading enzyme levels (1.86-fold, p < 0.001). Fructose supplementation reduced the expression of antioxidant enzymes and altered the amount of proteins involved in mitochondrial fusion/fission in the frontal cortex. In conclusion, cognitive deficits induced by chronic liquid fructose consumption are not exclusively related to increased caloric intake and are correlated with hypertriglyceridemia, impaired insulin signaling, increased oxidative stress and altered mitochondrial dynamics, especially in the frontal cortex.


Assuntos
Encéfalo/metabolismo , Frutose/administração & dosagem , Glucose/administração & dosagem , Insulina/metabolismo , Memória , Transdução de Sinais , Animais , Biomarcadores/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição , Comportamento de Ingestão de Líquido , Feminino , Teste de Tolerância a Glucose , Produtos Finais de Glicação Avançada/sangue , Hipocampo/metabolismo , Inflamação/patologia , Insulina/sangue , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Dinâmica Mitocondrial , Estresse Oxidativo , Córtex Pré-Frontal/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triglicerídeos/sangue
8.
Nutrients ; 9(3)2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-28294959

RESUMO

A high consumption of fat and simple sugars, especially fructose, has been related to the development of insulin resistance, but the mechanisms involved in the effects of these nutrients are not fully understood. This study investigates the effects of a Western-type diet and liquid fructose supplementation, alone and combined, on insulin signalling and inflammation in low-density lipoprotein (LDL) receptor-deficient mice (LDL-R-/-). LDL-R-/- mice were fed chow or Western diet ±15% fructose solution for 12 weeks. Plasma glucose and insulin, and the expression of genes related to inflammation in the liver and visceral white adipose tissue (vWAT), were analysed. V-akt murine thymoma viral oncogene homolog-2 (Akt) activation was measured in the liver of the mice after a single injection of saline or insulin. None of the dietary interventions caused inflammation in vWAT, whereas the Western diet induced hepatic inflammation, which was further enhanced by liquid fructose, leading also to a significant increase in fibrogenesis markers. However, there was no change in plasma glucose or insulin, or insulin-induced Akt phosphorylation. In conclusion, hepatic inflammation and fibrogenesis markers induced by a Western diet supplemented with liquid fructose in LDL-R-/- mice are not associated with a significant impairment of hepatic insulin signalling.


Assuntos
Biomarcadores/sangue , Dieta Ocidental/efeitos adversos , Frutose/efeitos adversos , Inflamação/fisiopatologia , Fígado/fisiopatologia , Receptor de Insulina/metabolismo , Proteínas da Fase Aguda/metabolismo , Tecido Adiposo Branco/fisiopatologia , Alanina Transaminase/sangue , Animais , Glicemia/metabolismo , Proteínas de Transporte/metabolismo , Frutose/administração & dosagem , Inflamação/etiologia , Insulina/sangue , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Fosforilação , Receptores de LDL/metabolismo , Transdução de Sinais
9.
J Nutr Biochem ; 40: 105-115, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27883935

RESUMO

BACKGROUND/OBJECTIVES: Liquid fructose associates with prevalence of type 2 diabetes mellitus and obesity. Intervention studies suggest that metabolically unfit individuals are more responsive than healthy individuals to liquid fructose. We determined whether mice consuming an obesogenic Western diet were more responsive than chow-fed mice to the alterations induced by liquid fructose supplementation (LFS). METHODS: C57BL/6N mice were fed chow or Western diet±ad libitum 15% fructose solution for 12 weeks. Food and liquid intake and body weight were monitored. Plasma analytes and liver lipids, histology and the expression of genes related to lipid handling, endoplasmic reticulum stress, inflammation and insulin signaling were analyzed. RESULTS: Western diet increased energy intake, visceral adipose tissue (vWAT), body weight, plasma and liver triglycerides and cholesterol, and inflammatory markers in vWAT vs. chow-fed mice. LFS did not change energy intake, vWAT or body weight. LFS significantly increased plasma and liver triglycerides and cholesterol levels only in Western-diet-fed mice. These changes associated with a potentiation of the increased liver expression of PPARγ and CD36 that was observed in Western-fed mice and related to the increased liver mTOR phosphorylation induced by LFS. Furthermore, LFS in Western-diet-fed mice induced the largest reduction in liver IRS2 protein and a significant decrease in whole-body insulin sensitivity. CONCLUSIONS: LFS in mice, in a background of an unhealthy diet that already induces fatty liver visceral fat accretion and obesity, increases liver lipid burden, hinders hepatic insulin signaling and diminishes whole-body insulin sensitivity without changing energy intake.


Assuntos
Colesterol/metabolismo , Dieta Ocidental/efeitos adversos , Frutose/efeitos adversos , Insulina/metabolismo , Fígado/metabolismo , Tecido Adiposo/patologia , Animais , Peso Corporal , Estresse do Retículo Endoplasmático , Ingestão de Energia , Frutose/química , Masculino , Camundongos Endogâmicos C57BL , Paniculite/etiologia , Transdução de Sinais/efeitos dos fármacos , Triglicerídeos/metabolismo
10.
Am J Physiol Heart Circ Physiol ; 312(2): H289-H304, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27923787

RESUMO

High consumption of simple sugars causes adverse cardiometabolic effects. We investigated the mechanisms underlying the metabolic and vascular effects of glucose or fructose intake and determined whether these effects are exclusively related to increased calorie consumption. Female Sprague-Dawley rats were supplemented with 20% wt/vol glucose or fructose for 2 mo, and plasma analytes and aortic response to vasodilator and vasoconstrictor agents were determined. Expression of molecules associated with lipid metabolism, insulin signaling, and vascular response were evaluated in hepatic and/or aortic tissues. Caloric intake was increased in both sugar-supplemented groups vs. control and in glucose- vs. fructose-supplemented rats. Hepatic lipogenesis was induced in both groups. Plasma triglycerides were increased only in the fructose group, together with decreased expression of carnitine palmitoyltransferase-1A and increased microsomal triglyceride transfer protein expression in the liver. Plasma adiponectin and peroxisome proliferator-activated receptor (PPAR)-α expression was increased only by glucose supplementation. Insulin signaling in liver and aorta was impaired in both sugar-supplemented groups, but the effect was more pronounced in the fructose group. Fructose supplementation attenuated aortic relaxation response to a nitric oxide (NO) donor, whereas glucose potentiated it. Phenylephrine-induced maximal contractions were reduced in the glucose group, which could be related to increased endothelial NO synthase (eNOS) phosphorylation and subsequent elevated basal NO in the glucose group. In conclusion, despite higher caloric intake in glucose-supplemented rats, fructose caused worse metabolic and vascular responses. This may be because of the elevated adiponectin level and the subsequent enhancement of PPARα and eNOS phosphorylation in glucose-supplemented rats. NEW & NOTEWORTHY: This is the first study comparing the effects of glucose and fructose consumption on metabolic factors and aortic function in female rats. Our results show that, although total caloric consumption was higher in glucose-supplemented rats, fructose ingestion had a greater impact in inducing metabolic and aortic dysfunction.


Assuntos
Aorta/efeitos dos fármacos , Sacarose na Dieta/farmacologia , Ingestão de Energia , Frutose/farmacologia , Glucose/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Acetilcolina/farmacologia , Adiponectina/metabolismo , Animais , Aorta/metabolismo , Aorta/fisiopatologia , Western Blotting , Bradicinina/farmacologia , Carnitina O-Palmitoiltransferase/efeitos dos fármacos , Carnitina O-Palmitoiltransferase/metabolismo , Proteínas de Transporte/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Feminino , Insulina/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/metabolismo , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Nitroprussiato/farmacologia , PPAR alfa/efeitos dos fármacos , PPAR alfa/metabolismo , Fenilefrina/farmacologia , Fosforilação , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Triglicerídeos/metabolismo , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
11.
Sci Rep ; 6: 26149, 2016 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-27194405

RESUMO

Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake.


Assuntos
Fígado Gorduroso/induzido quimicamente , Frutose/administração & dosagem , Glucose/administração & dosagem , Hipoglicemiantes/metabolismo , Insulina/metabolismo , Transdução de Sinais , Edulcorantes/metabolismo , Tecido Adiposo/patologia , Animais , Dieta/métodos , Fígado Gorduroso/patologia , Teste de Tolerância a Glucose , Fígado/patologia , Músculo Esquelético/patologia , Ratos
12.
Biochim Biophys Acta ; 1851(2): 107-16, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25463011

RESUMO

Supplementation with 10% liquid fructose to female rats for 2weeks caused hepatic steatosis through increased lipogenesis and reduced peroxisome proliferator activated receptor (PPAR) α activity and fatty acid catabolism, together with increased expression of the spliced form of X-binding protein-1 (Rebollo et al., 2014). In the present study, we show that some of these effects are preserved after sub-chronic (8weeks) fructose supplementation, specifically increased hepatic expression of lipid synthesis-related genes (stearoyl-CoA desaturase, ×6.7-fold; acetyl-CoA carboxylase, ×1.6-fold; glycerol-3-phosphate acyltransferase, ×1.65-fold), and reduced fatty acid ß-oxidation (×0.77-fold), resulting in increased liver triglyceride content (×1.69-fold) and hepatic steatosis. However, hepatic expression of PPARα and its target genes was not modified and, further, livers of 8-week fructose-supplemented rats showed no sign of unfolded protein response activation, except for an increase in p-IRE1 levels. Hepatic mTOR phosphorylation was enhanced (×1.74-fold), causing an increase in the phosphorylation of UNC-51-like kinase 1 (ULK-1) (×2.8-fold), leading to a decrease in the ratio of LC3B-II/LC3B-I protein expression (×0.39-fold) and an increase in the amount of the autophagic substrate p62, indicative of decreased autophagy activity. A harmful cycle may be established in the liver of 8-week fructose-supplemented rats where lipid accumulation may cause defective autophagy, and reduced autophagy may result in decreased free fatty acid formation from triglyceride depots, thus reducing the substrates for ß-oxidation and further increasing hepatic steatosis. In summary, the length of supplementation is a key factor in the metabolic disturbances induced by fructose: in short-term studies, PPARα inhibition and ER stress induction are critical events, whereas after sub-chronic supplementation, mTOR activation and autophagy inhibition are crucial.


Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Fígado Gorduroso/enzimologia , Frutose , Fígado/enzimologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Modelos Animais de Doenças , Ativação Enzimática , Ácidos Graxos/metabolismo , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Feminino , Regulação da Expressão Gênica , Glicólise/genética , Hipertrigliceridemia/induzido quimicamente , Hipertrigliceridemia/enzimologia , Hipertrigliceridemia/patologia , Lipogênese , Fígado/patologia , Oxirredução , PPAR alfa/metabolismo , Via de Pentose Fosfato/genética , Fosforilação , Ratos Sprague-Dawley , Transdução de Sinais , Fatores de Tempo , Triglicerídeos/metabolismo
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