Avaliação da trigonelina e curcumina, isoladas ou co-administradas em iogurte, em modelo experimental de obesidade e resistência à insulina
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Data
2019-05-31
Autores
Costa, Mariana de Campos da [UNESP]
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Universidade Estadual Paulista (Unesp)
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Introdução: Ativos naturais têm sido estudados por suas ações antioxidantes, anti-inflamamatórias e antiglicação, que podem ser interessantes para prevenir/atenuar as complicações da obesidade e do diabetes mellitus (DM). A curcumina (polifenol isolado de Curcuma longa L.) e a trigonelina (alcaloide isolado de Trigonella foenum-graecum L.) apresentam ações benéficas contra os sintomas e desordens da obesidade e do DM, e combatem as consequências deletérias relacionadas ao estresse glicoxidativo. Objetivo: Investigar, em camundongos submetidos ao modelo experimental de obesidade/resistência à insulina, os efeitos dos tratamentos com trigonelina e/ou curcumina em iogurte, avaliando alterações em parâmetros fisiológicos e bioquímicos, sinalização insulínica (AKT), programa termogênico e status energético [sirtuína 1 (SIRT 1), proteína quinase ativada por adenosina monofosfato (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), proteína desacopladora mitocondrial 1(UCP 1)], níveis de marcadores de estresse glicoxidativo [substâncias reativas ao ácido tiobarbitúrico (TBARS), produtos finais de glicação avançada (AGEs), receptor de AGEs (RAGE)], marcadores da inflamação [fator nuclear kappa B (NF-кB), interleucinas (IL)-6 (IL-6) e 10 (IL-10), fator de necrose tumoral (TNF-α)], potencial antioxidante [atividades de superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GSH-Px), nuclear factor (erythroid-derived 2)-like-2 factor (NRF 2)], maquinaria de detoxificação de AGEs [glioxalase 1 (GLO 1), receptor 1 de AGEs (AGE-R1)]. Metodologia: Camundongos C57BL/6 machos foram alimentados durante 9 semanas com dieta padrão (P; 3,85 kcal/g; 4% de lipídeos) ou hiperlipídica (H; 5,40 kcal/g; 35% de lipídeos) e tratados por via oral com iogurte enriquecido com trigonelina ou curcumina, isoladas ou combinadas. Na 7ª semana, foi realizado o teste tolerância à glicose oral (TTGO), e na 8ª semana o teste de tolerância à insulina (ITT). Na 9ª semana, os animais foram eutanasiados e amostras de plasma, tecidos adiposos brancos e marrom, músculo esquelético gastrocnemius, fígado e rim foram utilizados para a determinação dos níveis de biomarcadores de estresse glicoxidativo, inflamação, programa termogênico e status energético. Resultados: Os tratamentos com trigonelina ou curcumina em iogurte, de forma isolada, exerceram ações antihiperglicêmicas e antihiperlipidêmicas, melhoraram a tolerância à glicose e a sensibilidade à insulina. O tratamento com trigonelina desempenhou efeito importante na redução da ingestão alimentar e calórica, prevenção do ganho de massa corporal, atenuação da hipertrofia adipocítica; potencial anti-inflamatório no tecido adiposo epididimal (via redução nos níveis de NF-кB, IL-6, TNF-α e aumento de IL-10), o que pode ter contribuído para o aumento nos níveis de fosforiliação de AKT e maior sensibilidade à insulina. O tratamento com trigonelina também se destacou na prevenção do estresse glicoxidativo no rim (redução de TBARS, AGEs e RAGE), promoveu aumento de marcadores do status energético (SIRT 1, AMPK, PGC-1α), e apresentou potencial antioxidante (aumento de NRF 2, SOD, CAT e GSH-Px) e anti-inflamatório (redução de NF-кB, IL-6, TNF-α e aumento de IL-10). O tratamento com curcumina destacou-se na promoção de aumento nos níveis de fosforilação de AKT em músculo gastrocnemius, aumento nos níveis de expressão de marcadores do status energético e programa termogênico no fígado e tecido adiposo marrom (SIRT 1, AMPK, PGC-1α, NRF 2 e UCP 1), protegeu o fígado de danos glicoxidativos (redução de TBARS, AGEs, RAGE), apresentou potencial anti-inflamatório (redução de NF-кB, IL-6 e TNF-α e aumento de IL-10) e antioxidante (aumento de NRF 2, SOD, CAT e GSH-Px). A combinação de trigonelina e curcumina em iogurte prejudicou os efeitos benéficos dos ativos naturais quando administrados isoladamente em animais obesos, aumentando a intolerância a glicose e resistência à insulina e diminuindo os níveis de fosforilação de AKT em tecido adiposo e músculo esquelético. A combinação dos ativos naturais também contribuiu para o aumento da inflamação (NF-кB, IL-6 e TNF-α) no fígado e rim. Conclusão: Trigonelina e curcumina administradas isoladamente em iogurte promoveram melhorias nos distúrbios metabólicos causados pela dieta hiperlipídica. Os tratamentos com estes ativos naturais em iogurte, de forma isolada, podem contribuir para a prevenção ou atenuação das complicações observadas na obesidade.
Introduction: Natural actives have been studied for their antioxidant, anti-inflammatory, and antiglycation potentials, which may be interesting to prevent/attenuate the complications of obesity and diabetes mellitus (DM). Curcumin (polyphenol isolated from Curcuma longa L.) and trigonelline (alkaloid isolated from Trigonella foenum-graecum L.) have beneficial actions against the symptoms and disorders of obesity and DM, and act against the deleterious consequences related to glycoxidative stress. Objectives: To investigate the effects of treatments of mice submitted to the experimental model of obesity/insulin resistance with trigonelin and/or curcumin in yoghurt, evaluating the changes in physiological and biochemical parameters, insulin signaling (AKT), thermogenic program and energetic status [sirtuin 1 (SIRT 1), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated gamma coactivator 1-alpha receptor (PGC-1α), mitochondrial uncoupling protein 1 (UCP 1), advanced glycation end products (AGEs), receptor for AGEs (RAGE)], markers of inflammation [nuclear factor kappa B (NF-кB), interleukins (IL) IL-6 and IL-10, tumor necrosis factor (TNF-α)], antioxidant defenses [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), nuclear factor (erythroid-derived 2)-like-2 factor (NRF2)], AGEs detoxification machinery [glyoxalase 1 (GLO 1), AGE receptor 1 (AGE-R1)]. Methods: Male C57BL/6 mice were fed a standard diet (P, 3.85 kcal/g, 4% lipid) or high-fat diet (H, 5.40 kcal/g, 35% lipid) for 9 weeks, and treated with yoghurt enriched with trigonellin or curcumin, alone or in combination. In the 7th week, the oral glucose tolerance test (TTGO) was performed, and in the 8th week the insulin tolerance test (ITT). At the 9th week, the animals were euthanized and samples of plasma, white and brown adipose tissues, skeletal muscles gastrocnemius, liver and kidney were used to determine biomarkers levels of glycoxidative stress, inflammation, thermogenic program and energy status. Results: Treatments with trigonelline or curcumin in yoghurt, alone, had antihyperglycemic and antihyperlipidemic effects, improved both the glucose tolerance and insulin sensitivity. The treatment with trigonelline had an important effect in the reduction of the food and energy intake, prevention of the body mass gain, attenuation of adipocyte hypertrophy; antiinflammatory potential in epididymal adipose tissues (reduced levels of NF-κB, IL-6, TNF-α and increased levels of IL-10), which may be contributing to the increased AKT phosphorylation levels, and increased insulin sensitivity. The treatment with trigonelin also prevented glycoxidative stress in kidney (reduction of TBARS, AGEs and RAGE), increased the levels of markers related to energy status (SIRT 1, AMPK, PGC-1α), and had antioxidant (SOD, CAT and GSH-Px) and antiinflammatory (reduction of NF-κB, IL-6, TNF-α, and increase of IL-10) potentials. The treatment with curcumin promoted increase in the phosphorylation levels of AKT in gastrocnemius muscles, increased the levels of biomarker related to energy status and thermogenic program in liver and brown adipose tissue (SIRT 1, AMPK, PGC-1α, NRF-2 and UCP 1), protected the liver against glycoxidative damage (reduction of TBARS, AGEs, RAGE), and showed anti-inflammatory (reduction of NF-κB, 9 IL-6 and TNF-α and increased IL-10) and antioxidant (increase of NRF 2, SOD, CAT and GSH-Px) potentials. The combination of trigonelin and curcumin in yoghurt impaired the beneficial effects of the natural actives when administered alone in obese animals, increasing the glucose intolerance and the insulin resistance, and decreasing the phosphorylation levels of AKT in adipose tissue and skeletal muscle. The combination of the natural actives also contributed to increased inflammation (NF-κB, IL-6 and TNF-α) in the liver and kidney. Conclusion: Trigonellin and curcumin, administered alone in yoghurt, promoted many improvements in metabolic disorders caused by the high-fat diet. Treatments with these natural actives in yoghurt, alone, may contribute to the prevention or attenuation of the complications observed in obesity.
Introduction: Natural actives have been studied for their antioxidant, anti-inflammatory, and antiglycation potentials, which may be interesting to prevent/attenuate the complications of obesity and diabetes mellitus (DM). Curcumin (polyphenol isolated from Curcuma longa L.) and trigonelline (alkaloid isolated from Trigonella foenum-graecum L.) have beneficial actions against the symptoms and disorders of obesity and DM, and act against the deleterious consequences related to glycoxidative stress. Objectives: To investigate the effects of treatments of mice submitted to the experimental model of obesity/insulin resistance with trigonelin and/or curcumin in yoghurt, evaluating the changes in physiological and biochemical parameters, insulin signaling (AKT), thermogenic program and energetic status [sirtuin 1 (SIRT 1), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated gamma coactivator 1-alpha receptor (PGC-1α), mitochondrial uncoupling protein 1 (UCP 1), advanced glycation end products (AGEs), receptor for AGEs (RAGE)], markers of inflammation [nuclear factor kappa B (NF-кB), interleukins (IL) IL-6 and IL-10, tumor necrosis factor (TNF-α)], antioxidant defenses [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), nuclear factor (erythroid-derived 2)-like-2 factor (NRF2)], AGEs detoxification machinery [glyoxalase 1 (GLO 1), AGE receptor 1 (AGE-R1)]. Methods: Male C57BL/6 mice were fed a standard diet (P, 3.85 kcal/g, 4% lipid) or high-fat diet (H, 5.40 kcal/g, 35% lipid) for 9 weeks, and treated with yoghurt enriched with trigonellin or curcumin, alone or in combination. In the 7th week, the oral glucose tolerance test (TTGO) was performed, and in the 8th week the insulin tolerance test (ITT). At the 9th week, the animals were euthanized and samples of plasma, white and brown adipose tissues, skeletal muscles gastrocnemius, liver and kidney were used to determine biomarkers levels of glycoxidative stress, inflammation, thermogenic program and energy status. Results: Treatments with trigonelline or curcumin in yoghurt, alone, had antihyperglycemic and antihyperlipidemic effects, improved both the glucose tolerance and insulin sensitivity. The treatment with trigonelline had an important effect in the reduction of the food and energy intake, prevention of the body mass gain, attenuation of adipocyte hypertrophy; antiinflammatory potential in epididymal adipose tissues (reduced levels of NF-κB, IL-6, TNF-α and increased levels of IL-10), which may be contributing to the increased AKT phosphorylation levels, and increased insulin sensitivity. The treatment with trigonelin also prevented glycoxidative stress in kidney (reduction of TBARS, AGEs and RAGE), increased the levels of markers related to energy status (SIRT 1, AMPK, PGC-1α), and had antioxidant (SOD, CAT and GSH-Px) and antiinflammatory (reduction of NF-κB, IL-6, TNF-α, and increase of IL-10) potentials. The treatment with curcumin promoted increase in the phosphorylation levels of AKT in gastrocnemius muscles, increased the levels of biomarker related to energy status and thermogenic program in liver and brown adipose tissue (SIRT 1, AMPK, PGC-1α, NRF-2 and UCP 1), protected the liver against glycoxidative damage (reduction of TBARS, AGEs, RAGE), and showed anti-inflammatory (reduction of NF-κB, 9 IL-6 and TNF-α and increased IL-10) and antioxidant (increase of NRF 2, SOD, CAT and GSH-Px) potentials. The combination of trigonelin and curcumin in yoghurt impaired the beneficial effects of the natural actives when administered alone in obese animals, increasing the glucose intolerance and the insulin resistance, and decreasing the phosphorylation levels of AKT in adipose tissue and skeletal muscle. The combination of the natural actives also contributed to increased inflammation (NF-κB, IL-6 and TNF-α) in the liver and kidney. Conclusion: Trigonellin and curcumin, administered alone in yoghurt, promoted many improvements in metabolic disorders caused by the high-fat diet. Treatments with these natural actives in yoghurt, alone, may contribute to the prevention or attenuation of the complications observed in obesity.
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Palavras-chave
obesidade, trigonelina, curcumina, iogurte, estresse glicoxidativo, inflamação, trigonelline, curcumin, glycoxidative stress, inflammation