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1.
J Ethnopharmacol ; 264: 113360, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-32918993

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Labiatae; lemon balm) is a traditional medicinal plant with hypoglycemic and hypolipidemic effects; however, how it imparts its beneficial effects remains unclear. We thus hypothesized that the herbal extract ALS-L1023, isolated from Melissa officinalis, inhibits obesity and diabetes, and tested our hypothesis using Otsuka Long-Evans Tokushima fatty (OLETF) rats, which are an established animal model of type 2 diabetes. MATERIALS AND METHODS: In this study, 28-week-old OLETF rats were fed a high-fat diet for 4 weeks to induce a marked impairment of the insulin response and were treated with or without ALS-L1023. Subsequently, the variables and determinants of glucose metabolism and pancreatic function were assessed via blood analysis, histology, immunohistochemistry, and real-time polymerase chain reaction. RESULTS: The administration of ALS-L1023 resulted in a weight reduction without changes in food intake. It also markedly inhibited hyperglycemia and hypoinsulinemia, and restored ß-cell mass that was severely impaired in OLETF rats. There was a decrease in lipid accumulation in the liver and skeletal muscle of the obese rats after treatment with ALS-L1023. Concomitantly, there was an increase in the expression levels of fatty acid-oxidizing enzymes (AMPKα2, ACOX, MCAD, and VLCAD) in the liver and skeletal muscle after ALS-L1023 treatment. Furthermore, ALS-L1023 attenuated the pancreatic inflammation including the infiltration of CD68-positive macrophages and mast cells, in addition to attenuating the expression of inflammatory factors (IL-6 and CD68). CONCLUSIONS: These results suggest that treatment with ALS-L1023 may reduce weight gain, elevated glucose levels, and ß-cell loss, by changing the expression of fatty acid-oxidizing enzymes in the liver and skeletal muscle, including inflammatory factors in the pancreas. These findings indicate that ALS-L1023 may be an effective therapeutic strategy to treat human obesity and type 2 diabetes.


Asunto(s)
Glucemia/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Melissa , Obesidad/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Aumento de Peso/efectos de los fármacos , Animales , Glucemia/metabolismo , Diabetes Mellitus Tipo 2 , Dieta Alta en Grasa/efectos adversos , Relación Dosis-Respuesta a Droga , Células Secretoras de Insulina/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/fisiología , Obesidad/etiología , Obesidad/metabolismo , Extractos Vegetales/farmacología , Ratas , Ratas Endogámicas OLETF , Ratas Long-Evans , Aumento de Peso/fisiología
2.
J Oleo Sci ; 69(5): 495-502, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32378551

RESUMEN

We previously reported that soy ß-conglycinin (ßCG) improves obesity-induced metabolic abnormalities, but not obesity, in obese model Otsuka Long-Evans Tokushima fatty (OLETF) rats. In the present study, we aimed to investigate the effects of ßCG-derived peptide consumption on obesity and lipid abnormality in OLETF rats. To this end, wild-type Long-Evans Tokushima Otsuka and OLETF rats were provided a normal diet containing 20% casein for four weeks as a control. In addition, we prepared ßCG peptide by enzymatic hydrolysis, and OLETF rats were fed a diet in which half of the casein was replaced by ßCG peptide (ßCG peptide group). Consequently, rats in the ßCG peptide group showed decreased abdominal white adipose tissue weight and lipid content (serum and liver triglycerides, and serum and liver cholesterol) compared to control OLETF rats. Further analysis demonstrated that ßCG peptide consumption decreased lipogenic enzyme activity and increased lipolytic enzyme activity in the liver of OLETF rats. In addition, suppressive effects on both synthesis and absorption of cholesterol were observed in ßCG peptide-fed OLETF rats. These findings suggest that peptidization of ßCG enhanced the anti-obese and hypolipidemic effects of ßCG.


Asunto(s)
Antígenos de Plantas/farmacología , Antígenos de Plantas/uso terapéutico , Globulinas/farmacología , Globulinas/uso terapéutico , Glycine max/química , Metabolismo de los Lípidos/efectos de los fármacos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Fitoterapia , Proteínas de Almacenamiento de Semillas/farmacología , Proteínas de Almacenamiento de Semillas/uso terapéutico , Proteínas de Soja/farmacología , Proteínas de Soja/uso terapéutico , Animales , Antígenos de Plantas/aislamiento & purificación , Modelos Animales de Enfermedad , Globulinas/aislamiento & purificación , Masculino , Ratas Endogámicas OLETF , Proteínas de Almacenamiento de Semillas/aislamiento & purificación , Proteínas de Soja/aislamiento & purificación
3.
Nutrients ; 12(5)2020 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-32375323

RESUMEN

Type 2 diabetes mellitus (T2DM) is a metabolic disease associated with chronic low-grade inflammation that is mainly associated with lifestyles. Exercise and healthy diet are known to be beneficial for adults with T2DM in terms of maintaining blood glucose control and overall health. We investigated whether a combination of exercise and curcumin supplementation ameliorates diabetes-related cognitive distress by regulating inflammatory response and endoplasmic reticulum (ER) stress. This study was performed using male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (a spontaneous diabetes Type 2 model) and Long-Evans Tokushima Otsuka (LETO) rats (LETO controls) by providing them with exercise alone or exercise and curcumin in combination. OLETF rats were fed either a diet of chow (as OLETF controls) or a diet of chow containing curcumin (5 g/kg diet) for five weeks. OLETF rats exercised with curcumin supplementation exhibited weight loss and improved glucose homeostasis and lipid profiles as compared with OLETF controls or exercised OLETF rats. Next, we examined cognitive functions using a Morris water maze test. Exercise plus curcumin improved escape latency and memory retention compared to OLETF controls. Furthermore, OLETF rats exercised and fed curcumin had lower IL6, TNFα, and IL10 levels (indicators of inflammatory response) and lower levels of ER stress markers (BiP and CHOP) in the intestine than OLETF controls. These observations suggest exercise plus curcumin may offer a means of treating diabetes-related cognitive dysfunction.


Asunto(s)
Cognición , Disfunción Cognitiva/terapia , Curcumina/administración & dosificación , Curcumina/farmacología , Diabetes Mellitus Experimental/psicología , Diabetes Mellitus Experimental/terapia , Suplementos Dietéticos , Estrés del Retículo Endoplásmico , Condicionamiento Físico Animal/fisiología , Fitoterapia , Animales , Cognición/efectos de los fármacos , Disfunción Cognitiva/etiología , Diabetes Mellitus Experimental/complicaciones , Estrés del Retículo Endoplásmico/efectos de los fármacos , Glucosa/metabolismo , Homeostasis/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratas Endogámicas OLETF , Pérdida de Peso/efectos de los fármacos
4.
Brain Res ; 1740: 146834, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32304687

RESUMEN

To investigate the effect of electroacupuncture (EA) on cognitive function and insulin resistance (IR) in an Al/D-gal-induced aging model for Alzheimer's disease (AD) using Ostuka Long-Evans Tokushima Fatty (OLETF) rats. The Al/D-gal-OLETF rats for AD were randomly divided into the EA and non-EA groups. Cognitive function was assessed using the Morris water maze (MWM). The morphology of the hippocampal neurons was observed using hematoxylin & eosin (H&E) staining. Aß and total Tau in the hippocampus and cerebrospinal fluid (CSF) were detected using western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose (FPG) was determined using the glucose oxidase method. Plasma fasting insulin (FINS), serum C-peptide (C-P), and CSF insulin were detected using ELISA. The expression of the genes and proteins in the PI3K signaling pathway was detected using quantitative real-time PCR and WB. After EA intervention, the hippocampal Aß and total Tau protein levels, body weight, FPG, FINS, and C-P were significantly decreased. The MWM showed that the percentage of time in the target quadrant of the EA group was elevated in the probe test. The protein levels of p-IRS1, p-IRS2, IDE, and p-GSK3ß were significantly increased, while p-PI3K-p85α and p-Akt were decreased. In conclusion, EA improves cognitive function and insulin resistance in rat models of AD. The PI3K/Akt signaling pathway is involved in those changes.


Asunto(s)
Envejecimiento/metabolismo , Disfunción Cognitiva/metabolismo , Electroacupuntura/métodos , Resistencia a la Insulina/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Envejecimiento/genética , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/terapia , Animales , Disfunción Cognitiva/genética , Disfunción Cognitiva/terapia , Galactosa/genética , Galactosa/metabolismo , Masculino , Aprendizaje por Laberinto/fisiología , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Ratas Endogámicas OLETF , Ratas Long-Evans , Transducción de Señal/fisiología
5.
Biomed Res ; 41(1): 23-32, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32092737

RESUMEN

Mild hyperbaric treatment prevents type 2 diabetes progression due to increased oxygen concentration and blood flow in skeletal muscle. However, it remains unknown whether this treatment is effective during all stages of type 2 diabetes. This study aimed to investigate the influences of hyperbaric treatment at 1.3 atmospheres absolute (ATA) on hemodynamic response in various stages of type 2 diabetes. Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as models of type 2 diabetes and healthy controls, respectively. Glucose levels were significantly higher in OLETF rats than in LETO rats at all ages. Glucose intolerance gradually increased with age in OLETF rats. Insulin levels in OLETF rats were significantly higher at 20-week-old, however, were significantly lower at 60-week-old than in LETO rats. Oxy-Hb, total Hb, and StO2 in skeletal muscle were increased during hyperbaric treatment in both rats. The hemodynamic changes were significantly higher in OLETF rats than LETO rats, and those changes were also pronounced at 8-week-old compared with other age in OLETF rats. These results suggest that hyperbaric treatment at 1.3 ATA acts on pathophysiological factors and the efficacy could be found only in the early stage of type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/terapia , Hemodinámica , Oxigenoterapia Hiperbárica/métodos , Músculo Esquelético/patología , Animales , Glucemia/metabolismo , Peso Corporal , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Prueba de Tolerancia a la Glucosa , Insulina/metabolismo , Músculo Esquelético/metabolismo , Oxígeno/metabolismo , Oxígeno/uso terapéutico , Ratas , Ratas Endogámicas OLETF
6.
Nutrition ; 63-64: 45-50, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30928787

RESUMEN

OBJECTIVES: Chlorella is a type of unicellular green algae that contains various nutrients. Habitual exercise and chlorella treatment can improve insulin resistance in obese or diabetic animal models. However, the additive effects of combined chlorella intake and aerobic exercise training remain unclear. The aim of this study was to investigate whether a combination of chlorella intake and aerobic exercise training would produce greater effects on improving glycemic control in rats with type 2 diabetes. METHODS: Twenty-wk-old male rats with type 2 diabetes (Otsuka Long-Evans Tokushima Fatty [OLETF] rats) were randomly divided into four groups: sedentary control, aerobic exercise training (treadmill running for 1 h, 25m/min, 5 d/wk), chlorella intake (0.5% chlorella powder in normal diet), or combination of aerobic exercise training and chlorella intake for 8 wk (n = 7 per group). RESULTS: Chlorella intake and aerobic exercise training significantly decreased fasting blood glucose, insulin levels, and total glucose area under the curve during the oral glucose tolerance test and increased the insulin sensitivity index concomitant with muscle phosphatidylinositol-3 kinase (PI3K) activity, protein kinase B (Akt) phosphorylation, and glucose transporter 4 (GLUT4) translocation levels. Furthermore, a combination of chlorella intake and aerobic exercise training significantly further improved these effects compared with aerobic exercise training or chlorella intake alone. CONCLUSIONS: These results suggested that chlorella intake combined with aerobic exercise training had more pronounced effects on the improvement of glycemic control via further activation of muscle PI3K/Akt/GLUT4 signaling in rats with type 2 diabetes.


Asunto(s)
Chlorella , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/terapia , Suplementos Dietéticos , Condicionamiento Físico Animal/fisiología , Preparaciones de Plantas/farmacología , Animales , Glucemia/análisis , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Tipo 2/sangre , Prueba de Tolerancia a la Glucosa , Resistencia a la Insulina/fisiología , Masculino , Músculo Esquelético/metabolismo , Fosforilación , Polvos , Ratas , Ratas Endogámicas OLETF
7.
Physiol Rep ; 7(6): e14046, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30916457

RESUMEN

Resistance training (RT) has been known to be effective in maintaining and improving bone strength, which is based on bone mineral density (BMD) and bone quality. However, it is not clear whether RT is effective in improving bone strength in patients with type-2 diabetes mellitus (T2DM), who have a high risk of fracture. Therefore, we tested the effects of a 6-week RT regimen using percutaneous electrical stimulation in T2DM model rats, male Otsuka Long-Evans Tokushima Fatty (OLETF), and its control, Long-Evans Tokushima Otsuka (LETO). After 6 weeks of RT, tibial BMD in RT legs was significantly higher than that in control (CON) legs in both groups. In diaphyseal cortical bone, bone area/tissue area, and cortical thickness was significantly increased in RT legs compared with CON legs in both groups. Cortical porosity was highly observed in OLETF compared with LETO, but RT improved cortical porosity in both groups. Interestingly, trabecular number, trabecular thickness and trabecular space as well as BMD and bone volume/tissue volume in proximal tibial metaphyseal trabecular bone were significantly improved in RT legs compared with CON legs in both groups. In contrast, connectivity density and structural model index were not affected by RT. These results indicate that the 6-week RT regimen effectively increased BMD and improved bone quality in T2DM model rats as well as control rats. Therefore, RT may have the potential to improve bone strength and reduce fracture risk, even in patients with T2DM.


Asunto(s)
Densidad Ósea , Remodelación Ósea , Diabetes Mellitus Tipo 2/terapia , Entrenamiento de Fuerza , Tibia/fisiopatología , Animales , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/fisiopatología , Modelos Animales de Enfermedad , Terapia por Estimulación Eléctrica , Masculino , Ratas Endogámicas OLETF , Ratas Long-Evans , Tibia/diagnóstico por imagen , Factores de Tiempo
8.
J Oleo Sci ; 68(4): 339-350, 2019 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-30867392

RESUMEN

The physiological effects of dietary ß-conglycinin (ß-CON), one of the major components of soy protein (SOY), were examined in an obese animal model. Prior studies show that ß-CON intake decreases plasma triglycerides and visceral adipose tissue weight, and increases plasma adiponectin in rodents. Since plasma adiponectin is known to affect both lipid and glucose metabolism, feeding a diet containing ß-CON could modulate insulin sensitivity. Therefore, we examined the effects of dietary ß-CON on insulin sensitivity and blood glucose levels, as well as lipid metabolism in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats (pre-symptomatic stage of type 2 diabetes mellitus). Male OLETF rats (6 weeks old) were fed diets containing 20% protein such as casein (CAS), CAS replaced with soy protein (SOY), or ß-CON at a proportion of 50% for 13 weeks. Fasting blood glucose levels were measured every 3 weeks, and an insulin tolerance test (ITT; 0.75 IU/kg body weight) was conducted at week 12. During the feeding period, fasting blood glucose was comparable among the groups. Insulin sensitivity measured by the ITT revealed that the SOY and ß-CON diets decreased blood glucose levels at 30 min after intraperitoneal insulin injection (vs. CAS diet). In addition, the ß-CON diet increased plasma adiponectin concentrations, hepatic gene expression of insulin receptor substrate (IRS) 2, and muscle gene expression of adiponectin receptor 1 (AdipoR1) and IRS1, and with a decrease in plasma insulin concentration. Finally, the ß-CON diet decreased the mesenteric adipose tissue weight and liver triglyceride concentration compared to the CAS diet. These results suggest that the metabolic effects of dietary ß-CON are mediated by increasing plasma adiponectin to increase insulin sensitivity and influence the hepatic lipid metabolism in obese OLETF rats.


Asunto(s)
Tejido Adiposo/metabolismo , Antígenos de Plantas/administración & dosificación , Antígenos de Plantas/farmacología , Suplementos Dietéticos , Globulinas/administración & dosificación , Globulinas/farmacología , Resistencia a la Insulina/fisiología , Metabolismo de los Lípidos/efectos de los fármacos , Obesidad/metabolismo , Proteínas de Almacenamiento de Semillas/administración & dosificación , Proteínas de Almacenamiento de Semillas/farmacología , Proteínas de Soja/administración & dosificación , Proteínas de Soja/farmacología , Adiponectina/sangre , Animales , Glucemia/metabolismo , Modelos Animales de Enfermedad , Proteínas Sustrato del Receptor de Insulina/metabolismo , Hígado/metabolismo , Masculino , Ratas Endogámicas OLETF , Receptores de Adiponectina/metabolismo , Triglicéridos/sangre , Triglicéridos/metabolismo
9.
J Diabetes ; 10(9): 753-763, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29633563

RESUMEN

BACKGROUND: Humans and animals with type 2 diabetes mellitus (T2DM) exhibit low skeletal muscle oxidative capacity and impaired glucose metabolism. The aim of the present study was to investigate the effects of exposure to mild hyperbaric oxygen on these changes in obese rats with T2DM. METHODS: Five-week-old non-diabetic Long-Evans Tokushima Otsuka (LETO) and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into normobaric (LETO-NB and OLETF-NB) and mild hyperbaric oxygen (LETO-MHO and OLETF-MHO) groups. The LETO-MHO and OLETF-MHO groups received 1266 hPa with 36% oxygen for 3 h daily for 22 weeks. RESULTS: Fasting and non-fasting blood glucose, HbA1c, and triglyceride levels were lower in the OLETF-MHO group than in the OLETF-NB group (P < 0.05). In the soleus muscle, peroxisome proliferator-activated receptor δ/ß (Pparδ/ß), Pparγ, and PPARγ coactivator-1α (Pgc-1α) mRNA levels were lower in the OLETF-NB group than in all other groups (P < 0.05), whereas myogenin (Myog) and myogenic factor 5 (Myf5) mRNA levels were higher in the OLETF-MHO group than in the LETO-NB and OLETF-NB groups (P < 0.05). The soleus muscles in the OLETF-NB group contained only low-oxidative Type I fibers, whereas those in all other groups contained high-oxidative Type IIA and Type IIC fibers in addition to Type I fibers. CONCLUSIONS: Exposure to mild hyperbaric oxygen inhibits the decline in skeletal muscle oxidative capacity and prevents the hyperglycemia associated with T2DM. Pgc-1α, Myog, and Myf5 mRNA levels appear to be closely associated with skeletal muscle oxidative capacity in rats with T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Oxigenoterapia Hiperbárica , Hiperglucemia/terapia , Músculo Esquelético/metabolismo , Animales , Glucemia/metabolismo , Expresión Génica , Hemoglobina Glucada/metabolismo , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Masculino , Músculo Esquelético/crecimiento & desarrollo , Factor 5 Regulador Miogénico/genética , Miogenina/genética , Oxidación-Reducción , Receptores Activados del Proliferador del Peroxisoma/genética , Ratas , Ratas Endogámicas OLETF , Especificidad de la Especie
10.
PLoS One ; 12(9): e0182467, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28877164

RESUMEN

The radix of Scutellaria baicalensis (SB) is a herb widely used in traditional Chinese medicine to treat metabolic diseases. Several main components, including baicalin and wogonoside, possess anti-dyslipidemia, anti-obesity and anti-diabetic effects. We hypothesized that co-administration of SB extract and metformin exerts a better effect on obesity-induced insulin resistance and lipid metabolism than treatment with metformin alone. We compared the effect of metformin (100 mg/10 mL/kg/day) alone with co-administration of metformin (100 mg/5 mL/kg/day) and SB extract (200 mg/5 mL/kg/day) on Otsuka Long Evans Tokushima Fatty rats, a useful model of type II diabetes with obesity, and used Long-Evans Tokushima Otsuka rats as a control. Weight, fasting glucose, oral glucose tolerance test, intraperitoneal insulin tolerance test, and serum total cholesterol were measured after 12 weeks of drug administration. We observed a synergetic effect of metformin and SB on lowering cholesterol level by excretion of bile acid through feces. We found that this accompanied activation of FXR, CYP7A1 and LDLR genes and repression of HMGCR in the liver. Although there were no significant changes in BSH-active gut microbiota due to high variability, functional prediction with 16S sequences showed increased primary and secondary bile acid biosynthesis in the combination treatment group. Further study is needed to find the specific strains of bacteria which contribute to FXR-related cholesterol and bile acid regulations.


Asunto(s)
Ácidos y Sales Biliares/metabolismo , Homeostasis/efectos de los fármacos , Metformina/farmacología , Extractos Vegetales/farmacología , Algoritmos , Animales , Glucemia/metabolismo , Western Blotting , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Colesterol 7-alfa-Hidroxilasa/genética , Colesterol 7-alfa-Hidroxilasa/metabolismo , Terapia Combinada , Heces/química , Conducta Alimentaria/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Resistencia a la Insulina , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Metagenoma , Metformina/administración & dosificación , Filogenia , Extractos Vegetales/administración & dosificación , Análisis de Componente Principal , Ratas Endogámicas OLETF , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Scutellaria baicalensis , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética
11.
PLoS One ; 12(6): e0178428, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28575002

RESUMEN

Previous reports have shown that the early postnatal environment has the ability to modify the obesity phenotype of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. To determine whether this early postnatal environment affects hypothalamic signaling systems involved in energy balance, OLETF pups and lean Long-Evans Tokushima Otsuka (LETO) pups were cross-fostered to same or opposite strain Dams (designated as LdLp: LETO pups with LETO dams; LdOp: OLETF pups with LETO dams; OdLp: LETO pups with OLETF dams; and OdOp: OLETF pups with OLETF dams). Hypothalamic gene expression was examined at postnatal day 23 (PND 23) and PND 90 as OdOp rats started to gain more body weight at PND 23 and developed obesity at PND 90 relative to lean control LdLp rats. On PND 23, neuropeptide Y (Npy) gene expression was significantly increased in the dorsomedial hypothalamus (DMH) in both LdOp and OdOp pups compared to LdLp pups. Maternal environment did not affect DMH Npy expression in LETO weanlings. On PND 90, maternal environment during the cross-fostering period had a major effect on DMH Npy expression. Levels were significantly increased in both OdOp and OdLp rats relative to those in LdOp rats and LdLp controls. Reduced expression of Npy in the DMH of LdOp rats was consistent with their reduction of body weight compared to OdOp rats. In contrast to DMH Npy, gene expression for Npy and proopiomelanocortin in the arcuate nucleus appeared to appropriately respond to alterations in body weight and plasma leptin levels. Levels of oxytocin gene expression in the paraventricular nucleus were lower in offspring raised by LETO dams apparently responding to the higher DMH NPY levels. Together, our results demonstrate effects of both genotype and early postnatal environment on obesity of OLETF rats and further suggest an important role of DMH NPY in the development of obesity of OLETF rats.


Asunto(s)
Expresión Génica , Hipotálamo/metabolismo , Animales , Niño , Humanos , Ratas Endogámicas OLETF
12.
J Ethnopharmacol ; 195: 204-213, 2017 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-27845265

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatic steatosis has risen rapidly in parallel with a dramatic increase in obesity. The aim of this study was to determine whether the herbal composition Gambigyeongsinhwan (4) (GGH(4)), composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata, regulates hepatic steatosis and inflammation. MATERIALS AND METHODS: The effects of GGH(4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty (OLETF) rats and HepG2 cells were examined using Oil red O, hematoxylin and eosin, and toluidine blue staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay. RESULTS: Administration of GGH(4) to OLETF rats improved hepatic steatosis and lowered serum levels of alanine transaminase, total cholesterol, triglycerides, and free fatty acids. GGH(4) increased mRNA levels of fatty acid oxidation enzymes (ACOX, HD, CPT-1, and MCAD) and decreased mRNA levels of lipogenesis genes (FAS, ACC1, C/EBPα, and SREBP-1c) in the liver of OLETF rats. In addition, infiltration of inflammatory cells and expression of inflammatory cytokines (CD68, TNFα, and MCP-1) in liver tissue were reduced by GGH(4). Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, but GGH(4) inhibited lipid accumulation by regulating the expression of hepatic fatty acid oxidation and lipogenic genes. GGH(4) also increased PPARα reporter gene expression. These effects of GGH(4) were similar to those of the PPARα activator fenofibrate, whereas the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on lipid accumulation in HepG2 cells. CONCLUSIONS: These results suggest that GGH(4) inhibits obesity-induced hepatic steatosis and that this process may be mediated by regulation of the expression of PPARα target genes and lipogenic genes. GGH(4) also suppressed obesity-related hepatic inflammation. Thus, GGH(4) may be a promising drug for the treatment of obesity-related liver diseases.


Asunto(s)
Antiinflamatorios/farmacología , Hepatitis/tratamiento farmacológico , Hepatocitos/efectos de los fármacos , Hipolipemiantes/farmacología , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Extractos Vegetales/farmacología , Alanina Transaminasa/sangre , Animales , Biomarcadores/sangre , Citocinas/metabolismo , Modelos Animales de Enfermedad , Fenofibrato/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Hepatitis/sangre , Hepatitis/genética , Hepatocitos/enzimología , Humanos , Mediadores de Inflamación/metabolismo , Lípidos/sangre , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , Hígado/enzimología , Masculino , Ratones , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/genética , Obesidad/genética , Oxazoles/farmacología , PPAR alfa/genética , PPAR alfa/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Endogámicas OLETF , Transfección , Tirosina/análogos & derivados , Tirosina/farmacología
13.
Sci Rep ; 6: 24238, 2016 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-27053000

RESUMEN

Transthyretin (TTR) is a blood and cerebrospinal fluid transporter of thyroxine and retinol. Gene expression profiling revealed an elevation of Ttr expression in the dorsomedial hypothalamus (DMH) of rats with exercise-induced anorexia, implying that central TTR may also play a functional role in modulating food intake and energy balance. To test this hypothesis, we have examined the effects of brain TTR on food intake and body weight and have further determined hypothalamic signaling that may underlie its feeding effect in rats. We found that intracerebroventricular (icv) administration of TTR in normal growing rats decreased food intake and body weight. This effect was not due to sickness as icv TTR did not cause a conditioned taste aversion. ICV TTR decreased neuropeptide Y (NPY) levels in the DMH and the paraventricular nucleus (P < 0.05). Chronic icv infusion of TTR in Otsuka Long-Evans Tokushima Fatty rats reversed hyperphagia and obesity and reduced DMH NPY levels. Overall, these results demonstrate a previously unknown anorectic action of central TTR in the control of energy balance, providing a potential novel target for treating obesity and its comorbidities.


Asunto(s)
Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Hiperfagia/prevención & control , Obesidad/prevención & control , Prealbúmina/farmacología , Animales , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/metabolismo , Western Blotting , Células Cultivadas , Perfilación de la Expresión Génica/métodos , Hiperfagia/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Infusiones Intraventriculares , Masculino , Neuropéptido Y/metabolismo , Obesidad/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Prealbúmina/administración & dosificación , Prealbúmina/fisiología , Ratas Endogámicas OLETF , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
14.
J Gastroenterol ; 51(12): 1141-1149, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27025708

RESUMEN

BACKGROUND: It is widely understood that insulin resistance (IR) critically correlates with the development of liver fibrosis in several types of chronic liver injuries. Several experiments have proved that anti-IR treatment can alleviate liver fibrosis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules, improving IR. The aim of this study was to elucidate the effect of an SGLT2 inhibitor on the development of liver fibrosis using obese diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and their littermate nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. METHODS: Male OLETF and LETO rats were intraperitoneally injected with porcine serum twice a week for 12 weeks to augment liver fibrogenesis. Different concentrations of ipragliflozin (3 and 6 mg/kg) were orally administered during the experimental period. Serological and histological data were examined at the end of the experimental period. The direct effect of ipragliflozin on the proliferation of a human hepatic stellate cell (HSC) line, LX-2, was also evaluated in vitro. RESULTS: OLETF rats, but not LETO rats, received 12 weeks of porcine serum injection to induce severe fibrosis. Treatment with ipragliflozin markedly attenuated the development of liver fibrosis and expression of hepatic fibrosis markers, such as alpha smooth muscle actin, collagen 1A1, and transforming growth factor beta (TGF-ß), and improved IR in a dose-dependent manner in OLETF rats. In contrast, the proliferation of LX-2 in vitro was not affected, suggesting that ipragliflozin had no significant direct effect on the proliferation of HSCs. CONCLUSION: In conclusion, our dataset suggests that an SGLT2 inhibitor could alleviate the development of liver fibrosis by improving IR in naturally diabetic rats. This may provide the basis for creating new therapeutic strategies for chronic liver injuries with IR.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Cirrosis Hepática Experimental/etiología , Cirrosis Hepática Experimental/prevención & control , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Tiofenos/uso terapéutico , Animales , Peso Corporal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Diabetes Mellitus Experimental/patología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Glucósidos/administración & dosificación , Células Estrelladas Hepáticas/citología , Células Estrelladas Hepáticas/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Resistencia a la Insulina/fisiología , Hígado/patología , Cirrosis Hepática Experimental/patología , Masculino , Obesidad/complicaciones , Tamaño de los Órganos/efectos de los fármacos , Ratas Endogámicas OLETF , Transportador 2 de Sodio-Glucosa , Tiofenos/administración & dosificación
15.
Yonsei Med J ; 57(3): 664-73, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26996567

RESUMEN

PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Curcumina/farmacología , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Albuminuria , Animales , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Expresión Génica/efectos de los fármacos , Inflamación , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/fisiopatología , Glomérulos Renales/metabolismo , Glomérulos Renales/fisiopatología , Masculino , Malondialdehído/metabolismo , Malondialdehído/orina , Ratas , Ratas Endogámicas OLETF , Ratas Long-Evans , Superóxido Dismutasa/metabolismo
16.
Yonsei Medical Journal ; : 664-673, 2016.
Artículo en Inglés | WPRIM | ID: wpr-21847

RESUMEN

PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.


Asunto(s)
Animales , Masculino , Ratas , Albuminuria , Antiinflamatorios no Esteroideos/uso terapéutico , Curcumina/farmacología , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/complicaciones , Expresión Génica/efectos de los fármacos , Inflamación , Riñón/efectos de los fármacos , Glomérulos Renales/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Endogámicas OLETF , Ratas Long-Evans , Superóxido Dismutasa/metabolismo
17.
J Nutr Sci Vitaminol (Tokyo) ; 61(4): 313-21, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26440638

RESUMEN

It has been reported that postprandial hyperglycemia from the pre-diabetic stage, especially from the impaired glucose tolerance (IGT) stage, is positively associated with subsequent incidences of cardiovascular diseases (CVD) and type 2 diabetes. In this study, we aimed to investigate whether treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4I) or an α-glucosidase inhibitor (α-GI), either of which suppresses postprandial hyperglycemia, reduces the expression of CVD risk factors in an IGT animal model. A DPP-4I, anagliptin (1,200 ppm), or an α-GI, miglitol (600 ppm), in the diet was administered for 47 wk to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for spontaneously-developed type 2 diabetes, at the IGT stage. We examined whether each treatment reduced the expression of CVD risk factors such as inflammatory cytokines/cytokine-like factors in peripheral leukocytes and adhesion molecules in the aortic tissues and circulation. Treatment with either drug reduced IGT development and repressed expression of the interleukin-1ß, tumor necrosis factor-α, S100a9, and S100a11 genes in peripheral leukocytes in the fasting state at weeks 25 and 39. The mRNA levels of E-selectin in aortic tissues and protein levels of the soluble forms of E-selectin and ICAM-1 in arterial blood were significantly lower in the anagliptin and miglitol groups than in the control group. Our results suggest that long-term treatment with anagliptin or miglitol in OLETF rats at the IGT stage suppresses the expression of inflammatory cytokines in peripheral leukocytes and adhesion molecules in aortic tissues.


Asunto(s)
1-Desoxinojirimicina/análogos & derivados , Enfermedades Cardiovasculares/prevención & control , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Pirimidinas/administración & dosificación , 1-Desoxinojirimicina/administración & dosificación , Animales , Aorta/metabolismo , Glucemia/efectos de los fármacos , Enfermedades Cardiovasculares/etiología , Moléculas de Adhesión Celular/efectos de los fármacos , Citocinas/efectos de los fármacos , Ayuno/metabolismo , Hiperglucemia/complicaciones , Interleucina-1beta/metabolismo , Leucocitos/metabolismo , Masculino , Periodo Posprandial/efectos de los fármacos , Ratas , Ratas Endogámicas OLETF , Factores de Riesgo , Proteínas S100/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
18.
J Ethnopharmacol ; 171: 287-94, 2015 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-26068433

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Adipocyte lipid accumulation due to impaired fatty acid oxidation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. The aim of this study was to determine the antiobesity effects of the herbal composition Gambigyeongsinhwan (4) (GGH(4)) composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata. MATERIALS AND METHODS: The effects of GGH(4) and the individual components on lipid accumulation in 3T3-L1 adipocytes and body weight gain in Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined using Oil red O staining, hematoxylin and eosin staining, quantitative real-time PCR, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay. RESULTS: GGH(4), individual components, and an active principle of Curcuma longa curcumin inhibited lipid accumulation and mRNA levels of adipocyte-specific genes (PPARγ, aP2, and C/EBPα) in 3T3-L1 adipocytes compared with control cells. Treatment with GGH(4), the individual components or curcmumin increased mRNA levels of mitochondrial (CPT-1, MCAD, and VLCAD) and peroxisomal (ACOX and thiolase) PPARα target genes. GGH(4) and the individual components also increased PPARα reporter gene expression compared with control cells. These effects were most prominent in GGH(4)-treated cells. However, the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on adipogenesis. An in vivo study showed that GGH(4) decreased body weight gain, adipose tissue mass, and visceral adipocyte size with increasing mRNA levels of adipose tissue PPARα target genes in OLETF rats. CONCLUSIONS: These results demonstrate that GGH(4) has an antiobesity effects through the inhibition of adipocyte lipid accumulation, and this process may be mediated in part through adipose PPARα activation.


Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Obesidad/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Preparaciones de Plantas/uso terapéutico , Células 3T3-L1 , Alnus , Animales , Fármacos Antiobesidad/farmacología , Proteínas Potenciadoras de Unión a CCAAT/genética , Curcuma , Medicamentos Herbarios Chinos/farmacología , Proteínas de Unión a Ácidos Grasos/genética , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Medicina Tradicional Coreana , Ratones , Obesidad/metabolismo , Oxazoles/farmacología , PPAR alfa/antagonistas & inhibidores , PPAR gamma/genética , Fitoterapia , Extractos Vegetales/farmacología , Preparaciones de Plantas/farmacología , ARN Mensajero/metabolismo , Ratas Endogámicas OLETF , Triglicéridos/metabolismo , Tirosina/análogos & derivados , Tirosina/farmacología , Aumento de Peso/efectos de los fármacos
19.
Obes Res Clin Pract ; 9(2): 168-74, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25890430

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) has a variety of causes including calorie over-intake, an unbalanced diet, and/or genetic dysfunction of lipid metabolism. We hypothesized that NAFLD symptoms could be mitigated by specific nutritional factors. Here, we show that the potential for soy ß-conglycinin (ßCG) to improve obesity-induced metabolic abnormalities in the Otsuka Long Evans Tokushima fatty (OLETF) rat model of NAFLD. Long Evans Tokushima Otsuka (i.e., wild-type) and OLETF rats were provided a normal diet containing 20% casein for 4 weeks as a control. In a third (ßCG) group, OLETF rats were fed a diet in which half of the casein was replaced by ßCG. There was no difference in food intake between groups. Rats in the ßCG group had decreased liver weight and lipid content (triglycerides, cholesterol, and phospholipids) compared to controls. In addition, ßCG consumption decreased fatty acid synthase gene expression and enzymatic activity. These findings indicate that dietary intake of ßCG can improve obesity-induced metabolic dysfunction, possibly via suppression of de novo fatty acid synthesis.


Asunto(s)
Antígenos de Plantas/uso terapéutico , Proteínas en la Dieta/uso terapéutico , Globulinas/uso terapéutico , Glycine max/química , Lipogénesis/efectos de los fármacos , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Obesidad/metabolismo , Proteínas de Almacenamiento de Semillas/uso terapéutico , Proteínas de Soja/uso terapéutico , Animales , Antígenos de Plantas/farmacología , Proteínas en la Dieta/farmacología , Expresión Génica/efectos de los fármacos , Globulinas/farmacología , Lípidos/sangre , Lipogénesis/genética , Hígado/metabolismo , Masculino , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/complicaciones , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Endogámicas OLETF , Proteínas de Almacenamiento de Semillas/farmacología , Proteínas de Soja/farmacología
20.
J Nutr Biochem ; 26(3): 234-40, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25488547

RESUMEN

Bitter melon (BM; Momordica charantia) has been used as a treatment method for various diseases including cancer and diabetes. The objective of this study was to investigate whether BM has preventive effects against insulin resistance and diabetes and to identify the underlying mechanism by which BM ameliorates insulin resistance in obese and diabetic rats. The rats were separated into three groups as follows: (a) high-fat (HF) diet control, (b) HF diet and 1% BM and (c) HF diet and 3% BM. After 6 weeks of assigned treatments, body weight and food intake were not altered by BM administration. Bitter melon treatment significantly improved glucose tolerance and insulin sensitivity. The levels of proinflammatory cytokines were significantly down-regulated in liver, muscle and epididymal fats from BM-treated rats. The activation of nuclear factor-κB (NF-κB) in the liver and muscle was decreased by BM compared with HF controls. The 3% BM supplementation significantly increased the levels of phospho-insulin receptor substrate-1 (Tyr612) and phospho-Akt (Ser473). It also significantly decreased the levels of phospho-NF-κB (p65) (Ser536) and phospho-c-Jun N-terminal kinase (JNK) (Thr183/Tyr185) in liver, muscle and epididymal fats. The findings of this study indicate that BM exerted preventive effects against insulin resistance and diabetes through the modulation of NF-κB and JNK pathways. Therefore, BM may be useful in the prevention of insulin resistance and diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Suplementos Dietéticos , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina , Momordica charantia/química , Obesidad/fisiopatología , Extractos Vegetales/uso terapéutico , Tejido Adiposo Blanco/inmunología , Tejido Adiposo Blanco/metabolismo , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Núcleo Celular/inmunología , Núcleo Celular/metabolismo , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/etiología , Dieta Alta en Grasa/efectos adversos , Frutas/química , Hipoglucemiantes/administración & dosificación , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Hígado/inmunología , Hígado/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Músculo Esquelético/inmunología , Músculo Esquelético/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Obesidad/etiología , Obesidad/inmunología , Obesidad/metabolismo , Extractos Vegetales/administración & dosificación , Transporte de Proteínas , Ratas Endogámicas OLETF
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