Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle and glucose intolerance in high fat diet-fed mice

He, Huijun; Wang, Guoyu; Gao, Yuan; Liu, Wenhua; Zhong, Yu; Jin, Tianru

doi:10.4239/wjd.v3.i5.94

Cited by 208 publications

(151 citation statements)

References 37 publications

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“…In the leptin deficient ob/ob mice, which also develop obesity and type 2 diabetes, increased concentrations of lipid peroxidation products are seen in both plasma and skeletal muscle (78). Elevated protein and lipid oxidation products in adipose tissue, skeletal muscle, and/or liver have also been seen in mouse (39,42) and rat (62) models of diet-induced obesity. Measures of protein glycation, a form of oxidative damage that can occur at high concentrations of sugars (34,38), have been shown to increase in serum and adipose tissue of mice or rats fed high-fat diets (53,79,90).…”

Section: Obesity and Oxidative Stressmentioning

confidence: 88%

Redox regulation of insulin sensitivity due to enhanced fatty acid utilization in the mitochondria

Rindler

Crewe

Fernandes

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Rindler PM, Crewe CL, Fernandes J, Kinter M, Szweda LI. Redox regulation of insulin sensitivity due to enhanced fatty acid utilization in the mitochondria. Am J Physiol Heart Circ Physiol 305: H634 -H643, 2013. First published June 21, 2013; doi:10.1152/ajpheart.00799.2012.-Obesity enhances the risk for the development of type 2 diabetes and cardiovascular disease. Loss in insulin sensitivity and diminished ability of muscle to take up and use glucose are characteristics of type 2 diabetes. Paradoxically, regulatory mechanisms that promote utilization of fatty acids appear to initiate diet-induced insulin insensitivity. In this review, we discuss recent findings implicating increased mitochondrial production of the prooxidant H 2O2 due to enhanced utilization of fatty acids, as a signal to diminish reliance on glucose and its metabolites for energy. In the short term, the ability to preferentially use fatty acids may be beneficial, promoting a metabolic shift that ensures use of available fat by skeletal muscle and heart while preventing intracellular glucose accumulation and toxicity. However, with prolonged consumption of high dietary fat and ensuing obesity, the near exclusive dependence on fatty acid oxidation for production of energy by the mitochondria drives insulin resistance, diabetes, and cardiovascular disease. mitochondria; metabolic flexibility; redox signaling; insulin signaling; obesity THIS ARTICLE is part of a collection on Mitochondria in Cardiovascular Physiology and Disease. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.

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Section: Obesity and Oxidative Stressmentioning

confidence: 88%

Redox regulation of insulin sensitivity due to enhanced fatty acid utilization in the mitochondria

Rindler

Crewe

Fernandes

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…Nuclear and mitochondrial fractionation was performed as previously described [9] . Approximately 30 mg of tissue was homogenized in 1 mL of ice-cold buffer containing 20 mmol/L HEPES (pH 7.4), 250 mmol/L sucrose, 10 mmol/L KCl, 1.5 mmol/L MgCl 2 , 1 mmol/L EDTA, 1 mmol/L EGTA, 1 mmol/L dithiothreitol and the protease inhibitors (2 μg/mL aprotinin, 5 μg/mL leupeptin and 2 mmol/L phenyl methyl sulphonyl fluoride) (Sigma-Aldrich, Shanghai, China).…”

Section: Mitochondrial and Nuclear Fractionationmentioning

confidence: 99%

“…Nrf2 is activated by Nrf2 translocation from the cytoplasm to the nucleus, where it promotes the expression of a series of anti-oxidative enzymes, including a specifically regulated-protein, NADPH:quinone oxidoreductase-1 (NQO-1) [8] . We have previously observed a marked impairment of the Nrf2 system in mice fed a high-fat diet (HFD) [9,10] and that correcting defective Nrf2 function via supplementation with the chemical Nrf2 activator oltipraz not only attenuated oxidative stress but also improved insulin signaling and glucose metabolism [10] . Other synthetic chemical Nrf2 activators and natural Nrf2-activating compounds have also been shown to be effective in improving insulin action and glucose metabolism in various insulin-resistant models [9,[11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling

et al. 2016

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Aim: Accumulating evidence shows that lipopolysaccharides (LPS) derived from gut gram-negative bacteria can be absorbed, leading to endotoxemia that triggers systemic inflammation and insulin resistance. In this study we examined whether metformin attenuated endotoxemia, thus improving insulin signaling in high-fat diet fed mice. Methods: Mice were fed a high-fat diet for 18 weeks to induce insulin resistance. One group of the mice was treated with oral metformin (100 mg·kg -1 ·d -1 ) for 4 weeks. Another group was treated with LPS (50 μg·kg -1 ·d -1 , sc) for 5 days followed by the oral metformin for 10 d. Other two groups received a combination of antibiotics for 7 d or a combination of antibiotics for 7 d followed by the oral metformin for 4 weeks, respectively. Glucose metabolism and insulin signaling in liver and muscle were evaluated, the abundance of gut bacteria, gut permeability and serum LPS levels were measured. Results: In high-fat fed mice, metformin restored the tight junction protein occludin-1 levels in gut, reversed the elevated gut permeability and serum LPS levels, and increased the abundance of beneficial bacteria Lactobacillus and Akkermansia muciniphila. Metformin also increased PKB Ser473 and AMPK T172 phosphorylation, decreased MDA contents and redox-sensitive PTEN protein levels, activated the anti-oxidative Nrf2 system, and increased IκBα in liver and muscle of the mice. Treatment with exogenous LPS abolished the beneficial effects of metformin on glucose metabolism, insulin signaling and oxidative stress in liver and muscle of the mice. Treatment with antibiotics alone produced similar effects as metformin did. Furthermore, the beneficial effects of antibiotics were addictive to those of metformin. Conclusion: Metformin administration attenuates endotoxemia and enhances insulin signaling in high-fat fed mice, which contributes to its anti-diabetic effects.

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“…Igualmente, a administração de curcumina aumentou a sinalização do Nrf2 no músculo esquelético, atenuou a intolerância à glicose e diminuiu os níveis de malondialdeído (MDA) e ERO. Entretanto, os efeitos não foram observados no tecido adiposo branco e no fígado 34 . Acrescenta-se também, que animais com ativação excessiva do Nrf2 por meio da deleção genética de Keap1 mostraram supressão do aparecimento da obesidade e DM induzidos por dieta hiperlipídica, além de menor glicose e insulina plasmáticas e redução de esteatose hepática 35 .…”

Section: Nrf2 E Diabetesunclassified

O papel do fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) no diabetes mellitus

Hahn¹,

Oliveira²,

Bock³

2017

Clin. Biomed. Res.

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RESUMOO diabetes mellitus (DM) é uma doença metabólica complexa. Sua etiologia é atribuída a uma combinação entre fatores genéticos, ambientais e de estilo de vida. Contudo, sabe-se que o estresse oxidativo desempenha papel crucial na patogênese do DM, acarretando em disfunção das células β pancreáticas e resistência à insulina. Neste contexto, o fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) é considerado o regulador mestre da resposta antioxidante do organismo, sendo um mecanismo de importância crítica para a manutenção da homeostase e sobrevivência celular. Todavia, a função do Nrf2 não se limita somente à resposta antioxidante. Ao interagir com outras vias metabólicas, o Nrf2 possui importante papel na regulação do metabolismo, atuando no metabolismo dos lipídios, manutenção da glicemia, resposta inflamatória, entre outros. Entretanto, a exata relação do Nrf2 com outras vias metabólicas ainda não é totalmente conhecida. Contudo, sabe-se que o comprometimento da função do Nrf2 é evidente na fisiopatologia do DM bem como no desenvolvimento de suas complicações clínicas. A ativação do Nrf2 protege contra os danos mediados pelo DM, podendo ser adequada uma intervenção exógena para aumentar a sua atividade. Palavras-chave: Complicações do diabetes; estresse oxidativo; antioxidantes; inflamação; obesidade ABSTRACTDiabetes mellitus (DM) is a complex metabolic disease. Its etiology is attributed to a combination of genetic, environmental, and lifestyle factors. However, it is known that oxidative stress plays a crucial role in the pathogenesis of DM, leading to pancreatic β-cell dysfunction and insulin resistance. In this context, the nuclear factor-erythroid 2-related factor 2 (Nrf2) is considered the main regulator of the body's antioxidant response, being a mechanism of critical importance in the maintenance of homeostasis and cell survival. However, the role of Nrf2 is not limited to the antioxidant response alone. When interacting with other metabolic pathways, Nrf2 plays an important role in regulating metabolism, acting on lipid metabolism, in the maintenance of glycemia, and in inflammatory response, among others. However, the exact relationship of Nrf2 with other metabolic pathways is not yet fully understood. Nevertheless, impairment of Nrf2 function is known to be evident in the pathophysiology of DM as well as in the development of its clinical complications. Activation of the Nrf2 protects against damage mediated by DM, and an exogenous intervention may be adequate to increase its activity. Keywords: Diabetes complications; oxidative stress; antioxidants; inflammation; obesityO diabetes mellitus (DM) é uma doença metabólica crônica e progressiva que apresenta severas complicações. A sua principal característica clínica é a hiperglicemia crônica resultante de defeitos na secreção e/ou ação da insulina. De tal modo, a exposição crônica à hiperglicemia conduz a danos, disfunção e falência de diversos órgãos, afetando especialmente o coração, rins, olhos, nervos, ilhotas pancreáticas e vasos sanguí...

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Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle and glucose intolerance in high fat diet-fed mice

Cited by 208 publications

References 37 publications

Redox regulation of insulin sensitivity due to enhanced fatty acid utilization in the mitochondria

Redox regulation of insulin sensitivity due to enhanced fatty acid utilization in the mitochondria

Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling

O papel do fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) no diabetes mellitus

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