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1.
J Agric Food Chem ; 67(37): 10352-10360, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31503479

RESUMO

The potential for apple peels to mitigate the deleterious effects of a high-fat diet in mice was investigated here. Mice were fed a high-fat diet supplemented with apple powders from three apple varieties or a commercial apple polyphenol. Polyphenols were characterized using colorimetric assays and high-performance liquid chromatography. Mice were tested for standard metabolic parameters. There was a dose response to dietary apple peels, with the higher intake leading to reduced weight gain and adipose tissue mass relative to the lower intake, but none of the treatments were statistically different from the control. The gene expression of liver enzyme stearoyl-CoA desaturase (Scd-1) was correlated with adipose weight, and liver enzyme cytochrome P51 (Cyp51) was downregulated by the apple diets. The feces from a subset of mice were analyzed for polyphenols and for bacteria taxa by next-generation sequencing. The results revealed that the makeup of the fecal microbiota was related to the metabolism of dietary polyphenols.


Assuntos
Biflavonoides/análise , Catequina/análise , Fezes/química , Frutas/metabolismo , Microbioma Gastrointestinal , Malus/metabolismo , Obesidade/dietoterapia , Proantocianidinas/análise , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biflavonoides/metabolismo , Catequina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Frutas/química , Humanos , Masculino , Malus/química , Camundongos , Obesidade/genética , Obesidade/metabolismo , Obesidade/microbiologia , Polifenóis/análise , Polifenóis/metabolismo , Proantocianidinas/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Esterol 14-Desmetilase/genética , Esterol 14-Desmetilase/metabolismo
2.
Pestic Biochem Physiol ; 159: 68-79, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400786

RESUMO

Chlorpyrifos is a pesticide frequently detected in food and has been reported to disturb endocrine and gut health, which was regulated by gut microbiota and enteroendocrine cells. In this study, newly weaned (3 week) and adult (8 week) male rats fed a normal- or high- fat diet were chronically exposed to 0.3 mg chlorpyrifos/kg bodyweight/day. The effects of chlorpyrifos exposure on serum hormone levels, proinflammatory cytokines and gut microbiota were evaluated. Chronic exposure to chlorpyrifos significantly decreased the concentrations of luteinizing hormone, follicule stimulating hormone and testosterone, which was found only in the normal-fat diet. The counteracted effect of high-fat diet was also found in gut hormones and proinflammatory cytokines. Significantly higher concentrations of glucagon-like peptide-1, pancreatic polypeptide, peptide tyrosine tyrosine (PYY), ghrelin, gastric inhibitory poly-peptide, IL-6, monocyte chemoattractant protein-1, and TNF-α were found in rats exposed to chlorpyrifos beginning at newly weaned, whereas only the PYY, ghrelin and IL-6 concentrations increased significantly in rats exposed in adulthood. Furthermore, a decrease in epinephrine induced by chlorpyrifos exposure was found in rats exposed to chlorpyrifos beginning at newly weaned, regardless of their diet. Chlorpyrifos-induced disturbances in the microbiome community structure were more apparent in rats fed a high-fat diet and exposed beginning at newly weaned. The affected bacteria included short-chain fatty acid-producing bacteria (Romboutsia, Turicibacter, Clostridium sensu stricto 1, norank_f_Coriobacteriaceae, Faecalibaculum, Parasutterella and norank_f__Erysipelotrichaceae), testosterone-related genus (Turicibacter, Brevibacterium), pathogenic bacteria (Streptococcus), and inflammation-related bacteria (unclassified_f__Ruminococcaceae, Ruminococcaceae_UCG-009, Parasutterella, Oscillibacter), which regulated the endocrine system via the hypothalamic-pituitary-adrenal axis, as well as the immune response and gut barrier. Early exposure accelerated the endocrine-disturbing effect and immune responses of chlorpyrifos, although these effects can be eased or recovered by a high-fat diet. This study helped clarify the relationship between disrupted endocrine function and gut microbiota dysbiosis induced by food contaminants such as pesticides.


Assuntos
Clorpirifos/toxicidade , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/induzido quimicamente , RNA Ribossômico 16S/metabolismo , Envelhecimento , Animais , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Inflamação/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos
3.
Pharm Res ; 36(10): 141, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31367840

RESUMO

PURPOSE: The purpose of the present study was to investigate changes of blood-brain barrier (BBB) and brain parenchymal protein expression due to type II diabetes mellitus (T2DM) induced by a high-fat diet (HFD) by using SWATH-based quantitative proteomics. METHODS: Mice were fed a HFD for 2 or 10 weeks, and then SWATH-based quantitative proteomic analysis, western blot analysis, immunohistochemistry and functional transport studies were performed. RESULTS: In brain capillaries, expression levels of BBB transporters (Glut1, P-glycoprotein) and tight-junction proteins (claudin-5, occludin) were significantly reduced in HFD mice at 2 weeks, but recovered to the levels in the normal diet (ND) group at 10 weeks. P-glycoprotein function at the BBB was reduced at 2 weeks. In the cerebral cortex and hippocampus, neurofilament, which is important for neuronal function, was decreased in HFD mice at 2 weeks, but recovered at 10 weeks. CONCLUSION: Our results suggest that changes in the status of insulin resistance influence expression of BBB transporters, which in turn may alter the expression of cognitive function-related proteins.


Assuntos
Encéfalo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina , Insulina/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/irrigação sanguínea , Capilares/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Filamentos Intermediários/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteômica , Proteínas de Junções Íntimas/metabolismo
4.
Adv Exp Med Biol ; 1155: 133-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468392

RESUMO

Metabolic syndrome is a lifestyle-related disease caused by high nutrient condition and lack of exercise. The insulin resistance due to obesity has attracted attention as an underlying mechanism of metabolic syndrome. Insulin resistance refers to reduced insulin sensitivity in insulin target tissues. In this case, in order to maintain normal blood glucose levels, a compensatory large amount of insulin is released, leading to the occurrence of hyperinsulinemia. Taurine is widely distributed in animal tissues. Although it is not involved in protein synthesis, taurine plays an important role in maintaining the body's physiological function. In this experiment, insulin resistance model was induced by high fat and high sugar diet. Two percent taurine was added in drinking water to explore the mechanism of taurine in insulin resistance and to provide theoretical basis for using taurine to improve insulin resistance. The result showed that high-fat and high-sugar diet could decrease insulin sensitivity, and taurine could improve it by oral glucose tolerance test. Moreover, serum TG, TC were higher, while HDL-C in rats fed with high sugar and high fat diet was lower than normal rats, the changes of which can be significantly relieved by 2% taurine administration. mRNA and protein expressions of IRS1, and GLUT4 which were significantly changed by high sugar and high fat diet can also be regulated by 2% taurine. The results indicated that taurine can improve insulin sensitivity through remediating lipid metabolism disorder and regulating the expressions of IRS and GLUT4.


Assuntos
Resistência à Insulina , Metabolismo dos Lipídeos , Músculo Esquelético/efeitos dos fármacos , Taurina/farmacologia , Animais , Dieta Hiperlipídica/efeitos adversos , Açúcares da Dieta/efeitos adversos , Músculo Esquelético/fisiologia , Ratos
5.
Bratisl Lek Listy ; 120(8): 593-600, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379183

RESUMO

OBJECTIVES: The incidence of obesity and obesity-assosiated pathologies continues to increase with profound adverse effects on health status in the developed countries. BACKGROUND: We aimed to investigate the effect of high fat diet on the adrenal gland morphology. METHODS: We fed the mice with either high-fat diet (60 % kcal from fat) or low-fat diet (10 % kcal from fat) for nine weeks. Unbiased stereological methods were used to evaluate the adrenal gland morphology. The sections were evaluated using Cavalieri's method and volume fraction approach. We calculated mean volume of adrenal gland, mean volume of adrenal medulla, VVadrenal medulla/adrenal gland, mean diameter of cromaffin cells, number of chromaffin cells in per unit volume (NVcc mm‒3), total number of cromaffin cells, VVzona glomerulosa/adrenal cortex, VVzona fasciculata/adrenal cortex , VVzona reticulosa/adrenal cortex. RESULTS: The weight of adrenal gland, body weight intraperitoneal adipose tissue and adrenal gland weight in the obese mice significantly increased when compared with the control group. No changes were observed in the mean volume of adrenal gland, mean volume of adrenal medulla, VVzona glomerulosa/adrenal cortex, VVzona fasciculata/adrenal cortex, total number of cromaffin cells and diameter of cromaffin cells. However, NVcc mm-3 and VVzona reticulosa/adrenal cortex in the obese mice considerably increased compared with the control group. CONCLUSION: The present results suggest that high fat diet adversely affects the adrenal gland morphology (Tab. 2, Fig. 6, Ref. 28).


Assuntos
Glândulas Suprarrenais/patologia , Dieta Hiperlipídica/efeitos adversos , Córtex Suprarrenal/patologia , Medula Suprarrenal/patologia , Animais , Peso Corporal , Camundongos , Tamanho do Órgão
6.
Biomed Environ Sci ; 32(6): 406-418, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262386

RESUMO

OBJECTIVE: Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy. METHODS: In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected. RESULTS: The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism. CONCLUSION: It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.


Assuntos
Autofagia/efeitos dos fármacos , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Metabolismo dos Lipídeos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos Wistar , Fator de Transcrição STAT1/metabolismo , TYK2 Quinase/metabolismo
7.
Life Sci ; 230: 188-196, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150686

RESUMO

AIMS: Hyperoxia has beneficial metabolic effects in type 2 diabetes. However, hyperoxia exacerbates already existing oxidative stress in type 2 diabetes. Nitrate, a nitric oxide donor, is an effective new treatment in type 2 diabetes and also has antioxidant properties. The aim of this study was to determine whether nitrate administration can attenuate hyperoxia-induced oxidative stress in obese type 2 diabetic rats. MAIN METHODS: Fifty-six male Wistar rats (190-210 g) were divided into 8 groups: Controls (non-treated, nitrate-treated, O2-treated, and nitrate + O2-treated) and diabetes (non-treated, nitrate-treated, O2-treated, and nitrate + O2-treated). Diabetes was induced using high-fat diet and low-dose of streptozotocin (30 mg/kg). Rats in intervention groups, were exposed to 95% oxygen and consumed sodium nitrate (100 mg/L) in drinking water. Serum fasting glucose, oxidized (GSSG) and reduced (GSH) glutathiones, total oxidant status (TOS), catalase and superoxide dismutase (SOD) activities, and total antioxidant capacity (TAC) were measured after intervention. Oxidative stress index (OSI) was calculated as TOS/TAC ratio. KEY FINDINGS: Diabetic rats had increased oxidative stress and hyperoxia exacerbated it. In O2-diabetic rats, nitrate decreased GSSG (102.7 ±â€¯2.1 vs. 236.0 ±â€¯20.1 µM, P < 0.001), TOS (67.7 ±â€¯7.3 vs. 104 ±â€¯3.8 µM, P < 0.001), and OSI (0.44 ±â€¯0.04 vs. 0.91 ±â€¯0.07, P < 0.001) and increased catalase (2.8 ±â€¯0.13 vs. 1.8 ±â€¯0.21 KU/L, P = 0.014), SOD (53.4 ±â€¯1.5 vs. 38.4 ±â€¯1.2 U/mL, P < 0.001), GSH (43.7 ±â€¯1.4 vs. 17.8 ±â€¯0.5 mM, P = 0.003), TAC (152.5 ±â€¯1.9 vs. 116.7 ±â€¯5.0 mM, P < 0.001), and GSH/GSSG ratio (0.43 ±â€¯0.01 vs. 0.08 ±â€¯0.01, P = 0.005). Nitrate also potentiated effects of hyperoxia on decreasing fasting glucose. SIGNIFICANCE: Our results showed that dietary nitrate attenuates hyperoxia-induced oxidative stress in type 2 diabetic rats.


Assuntos
Nitratos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Glicemia/análise , Catalase/análise , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Glucose/metabolismo , Glutationa/análise , Hiperóxia/tratamento farmacológico , Hiperóxia/metabolismo , Masculino , Nitratos/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/análise
8.
Int. j. morphol ; 37(2): 438-447, June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1002240

RESUMO

Obesity is a modifiable risk factor for the development and progression of kidney disease. Obesity may harm kidneys in individuals without hypertension, diabetes, or pre-existing renal disease. Ginger, Zingiber officinale, has many beneficial pharmaceutical benefits. This study aimed to evaluate the Zingiber officinale protective effect against obesity complications which induced by high fat diet and caused renal dysfunctions. The study period was two months, and the experimental animals' groups were four, 80 Wistar rats were appropriated similarly 20 animals/group: control group; ginger extract group (GE); high-fat diet (HFD); and GE+HFD group. Body and fat weight, creatinine, leptin, TNF-α, total antioxidants, renal histopathological and ultrastructure were investigated. Rats in group of HFD showed a significant increase (P<0.05) in the body and fat weights, creatinine, leptin and TNF-α, and significant decrease (P<0.05) in total antioxidants (TAS). Ginger administration significantly showed the protective restoring the altered parameters. Furthermore, rats co-treated with ginger extract improved the histopathological and ultrastructural renal injury induced by obesity. The study concluded that the ginger extract used could suppress and decrease the renal damage induced by high-fat diet as it possesses potential medicinal values.


La obesidad es un factor de riesgo modificable para el desarrollo y la progresión de la enfermedad renal. La obesidad puede dañar los riñones en personas sin hipertensión, diabetes o enfermedad renal preexistente. El jengibre, Zingiber officinale, tiene muchos beneficios farmacéuticos. Este estudio tuvo como objetivo evaluar el efecto protector de Zingiber officinale en las complicaciones de la obesidad inducida por una dieta alta en grasas y las enfermedad renal. El período de estudio fue de dos meses, y los grupos de animales experimentales fueron cuatro, se asignaron 80 ratas Wistar de manera similar, 20 animales por grupo: grupo de control; grupo de extracto de jengibre (GE); dieta alta en grasas (DAG); y el grupo GE + DAG. Se evaluó el peso corporal y la grasa, creatinina, leptina, TNF-α, antioxidantes totales, histopatología renal y ultraestructura. Las ratas en el grupo de DAG mostraron un aumento significativo (P<0,05) en el peso corporal y de grasa, creatinina, leptina y TNF-a, y una disminución significativa (P<0,05) en los antioxidantes totales. La administración de jengibre mostró una protección significativa restaurando los parámetros alterados. Además, las ratas tratadas conjuntamente con extracto de jengibre mejoraron la lesión renal histopatológica y ultraestructural inducida por la obesidad. El estudio concluyó que el extracto de jengibre podría suprimir y disminuir el daño renal inducido por la dieta alta en grasas, ya que posee potenciales valores medicinales.


Assuntos
Animais , Ratos , Extratos Vegetais/farmacologia , Gengibre/química , Dieta Hiperlipídica/efeitos adversos , Nefropatias/tratamento farmacológico , Obesidade/complicações , Peso Corporal , Fator de Necrose Tumoral alfa/análise , Ratos Sprague-Dawley , Creatinina/análise , Leptina/análise , Microscopia Eletrônica de Transmissão , Rim/patologia , Nefropatias/patologia
9.
Nat Commun ; 10(1): 2717, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222048

RESUMO

Hepatic steatosis develops when lipid influx and production exceed the liver's ability to utilize/export triglycerides. Obesity promotes steatosis and is characterized by leptin resistance. A role of leptin in hepatic lipid handling is highlighted by the observation that recombinant leptin reverses steatosis of hypoleptinemic patients with lipodystrophy by an unknown mechanism. Since leptin mainly functions via CNS signaling, we here examine in rats whether leptin regulates hepatic lipid flux via the brain in a series of stereotaxic infusion experiments. We demonstrate that brain leptin protects from steatosis by promoting hepatic triglyceride export and decreasing de novo lipogenesis independently of caloric intake. Leptin's anti-steatotic effects are generated in the dorsal vagal complex, require hepatic vagal innervation, and are preserved in high-fat-diet-fed rats when the blood brain barrier is bypassed. Thus, CNS leptin protects from ectopic lipid accumulation via a brain-vagus-liver axis and may be a therapeutic strategy to ameliorate obesity-related steatosis.


Assuntos
Leptina/metabolismo , Fígado/metabolismo , Bulbo/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Triglicerídeos/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Humanos , Infusões Intraventriculares , Injeções Intraventriculares , Leptina/administração & dosagem , Lipogênese/fisiologia , Lipoproteínas VLDL , Fígado/inervação , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Polietilenoglicóis/administração & dosagem , Ratos , Ratos Sprague-Dawley , Técnicas Estereotáxicas , Simpatectomia , Nervo Vago/fisiologia , Nervo Vago/cirurgia
10.
Yakugaku Zasshi ; 139(6): 861-866, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31155526

RESUMO

Brown adipose tissue is a critical regulator of metabolic health, and contributes to thermogenesis by uncoupling oxidative phosphorylation through the action of mitochondrial uncoupling protein 1 (Ucp1). Recent studies have shown that cold exposure and the stimulation of ß3-adrenergic receptors induce the development of brown cell-like "beige" adipocytes in white adipose tissue. Brown and/or beige adipocyte-mediated thermogenesis suppresses high-fat diet-associated obesity. Therefore, the development of brown/beige adipocytes may prevent obesity and metabolic diseases. In the present study, we elucidated whether naturally occurring compounds contribute to regulating the cellular differentiation of brown/beige adipocytes. We screened for the up-regulated expression of Ucp1 during beige adipogenesis using extracts of crude herbal drugs frequently used in Kampo prescriptions (therapeutic drugs in Japanese traditional medicine). This screening revealed that the extract prepared from Citri Unshiu Pericarpium [the peel of Citrus unshiu (Swingle) Marcov.] increased the expression of Ucp1 in beige adipocytes. We also focused on the function of clock genes in regulating brown/beige adipogenesis. Therefore, another aim of the present study was to evaluate naturally occurring compounds that regulate brain and muscle Arnt-like 1 (Bmal1) gene expression. In this review, we focus on naturally occurring compounds that affect regulatory processes in brown/beige adipogenesis, and discuss better preventive strategies for the management of obesity and other metabolic disorders.


Assuntos
Fatores de Transcrição ARNTL , Adipócitos Bege/fisiologia , Adipócitos Marrons/fisiologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Diferenciação Celular , Medicamentos de Ervas Chinesas/farmacologia , Proteína Desacopladora 1 , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/fisiologia , Animais , Relógios Biológicos/genética , Temperatura Baixa , Dieta Hiperlipídica/efeitos adversos , Expressão Gênica , Humanos , Medicina Kampo , Doenças Metabólicas/prevenção & controle , Obesidade/etiologia , Obesidade/prevenção & controle , Fosforilação Oxidativa , Receptores Adrenérgicos beta 3/metabolismo , Termogênese , Proteína Desacopladora 1/metabolismo
11.
J Agric Food Chem ; 67(25): 7040-7049, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31199141

RESUMO

Obesity is a metabolic syndrome worldwide that causes many chronic diseases. Recently, we found an antiobesity effect of flaxseed polysaccharide (FP), but the mechanism remains to be elucidated. In this study, rats were first induced to develop obesity by being fed a high-fat diet. The obese rats were then fed a control diet, AIN-93M (group HFD), or a 10% FP diet (group FPD). The body weight, body fat, adipose tissue and liver sections, serous total triglycerides, levels of fasting blood glucose in serum, serous insulin, inflammatory cytokines in serum, and serous proteins within the leptin-neuropeptide Y (NPY) and AMP-activated protein kinase (AMPK) signaling pathway were determined and analyzed. FP intervention significantly reduced body weight and abdominal fat from 530 ± 16 g and 2.15% ± 0.30% in group HFD to 478 ± 10 g and 1.38% ± 0.48% in group FPD, respectively. This effect was achieved by removing leptin resistance possibly by inhibiting inflammation and recovering satiety through the significant downregulation of NPY and the upregulation of glucagon-like peptide 1. Adiponectin was then significantly upregulated probably via the gut-brain axis and further activated the AMPK signaling pathway to improve lipid metabolism including the improvement of lipolysis and fatty acid oxidation and the suppression of lipogenesis. This is the first report of the proposed antiobesity mechanism of FP, thereby providing a comprehensive understanding of nonstarch polysaccharides and obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Linho/química , Leptina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Saciação/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Obesidade/metabolismo , Obesidade/psicologia , Extratos Vegetais/química , Polissacarídeos/química , Ratos , Ratos Wistar , Sementes/química , Transdução de Sinais/efeitos dos fármacos
12.
J Agric Food Chem ; 67(25): 7073-7081, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240927

RESUMO

Obesity has been demonstrated as a disruptor of female fertility. Our previous study showed the antiobesity effects of calcium on HFD-fed male mice. However, the role of calcium in alleviating reproductive dysfunction of HFD-fed female mice remains unclear. Here, we found that HFD led to estrus cycle irregularity (longer cycle duration and shorter estrus period) and subfertility (longer conception time, lower fertility index, and less implantations) in mice. However, the HFD-induced reproductive abnormality was alleviated by calcium supplementation. Additionally, calcium supplementation enhanced activation/thermogenesis of BAT and browning of WAT in HFD-fed mice. Consequently, the abnormality of energy metabolism and glucose homeostasis induced by HFD were improved by calcium supplementation, with elevated metabolic rates and core temperature. In conclusion, these data showed that calcium supplementation alleviated HFD-induced estrous cycle irregularity and subfertility associated with concomitantly enhanced BAT thermogenesis and WAT browning, suggesting the potential application of calcium in improving obesity-related reproductive disorders.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/fisiopatologia , Cálcio/administração & dosagem , Ciclo Estral/efeitos dos fármacos , Doenças dos Genitais Femininos/tratamento farmacológico , Infertilidade/tratamento farmacológico , Obesidade/complicações , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/análise , Metabolismo Energético/efeitos dos fármacos , Feminino , Doenças dos Genitais Femininos/etiologia , Doenças dos Genitais Femininos/metabolismo , Doenças dos Genitais Femininos/fisiopatologia , Humanos , Infertilidade/etiologia , Infertilidade/metabolismo , Infertilidade/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
13.
J Agric Food Chem ; 67(25): 7136-7146, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240929

RESUMO

Benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) are organosulfur phytochemicals rich in cruciferous vegetables. We investigated the antiobesity and antihepatosteatosis activities of BITC and PEITC and the working mechanisms involved. C57BL/6J mice were fed a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.5 (L) or 1 g/kg (H) BITC or PEITC for 18 weeks. Compared with the HFD group, BITC or PEITC decreased the final body weight of mice in a dose-dependent manner [39.0 ± 3.1 (HFD), 34.4 ± 3.2 (BITC-L), 32.4 ± 2.8 (BITC-H), 36.2 ± 4.4 (PEITC-L), and 32.8 ± 2.9 (PEITC-H) g, p < 0.05], relative weight of epididymal fat [5.7 ± 0.4 (HFD), 4.7 ± 0.7 (BITC-L), 3.7 ± 0.3 (BITC-H), 4.4 ± 1.0 (PEITC-L), and 3.2 ± 0.6 (PEITC-H) %, p < 0.05], hepatic triglycerides [98.4 ± 6.0 (HFD), 81.0 ± 8.9 (BITC-L), 63.5 ± 5.6 (BITC-H), 69.3 ± 5.6 (PEITC-L), and 49.4 ± 2.9 (PEITC-H) mg/g, p < 0.05], and plasma total cholesterol [140 ± 21.3 (HFD), 109 ± 5.6 (BITC-L), 101 ± 11.3 (BITC-H), 126 ± 8.3 (PEITC-L), and 91.8 ± 12.7 (PEITC-H) mg/dL, p < 0.05]. Q-PCR and immunoblotting assays revealed that BITC and PEITC suppressed the expression of liver X receptor α, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase 1, fatty acid synthase, and acetyl-CoA carboxylase in both epididymal adipose and liver tissues. After a single oral administration of 85 mg/kg BITC or PEITC, the maximum plasma concentrations ( Cmax) of BITC and PEITC were 5.8 ± 2.0 µg/mL and 4.3 ± 1.9 µg/mL, respectively. In 3T3-L1 adipocytes, BITC and PEITC dose-dependently reduced adipocyte differentiation and cell cycle was arrested in G0/G1 phase. These findings indicate that BITC and PEITC ameliorate HFD-induced obesity and fatty liver by down-regulating adipocyte differentiation and the expression of lipogenic transcription factors and enzymes.


Assuntos
Adipogenia/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Isotiocianatos/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/fisiopatologia
14.
Chem Biol Interact ; 310: 108719, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31238026

RESUMO

Both obesity and arsenic exposure are global public health problems that are associated with increased risk of renal disease. The effect of whole-life exposure to environmentally relevant levels of arsenic within dietary high fat diet on renal pathogenesis were examined. In this study, C57BL/6 J mice were parentally exposed to 100 ppb arsenic before conception. After weaning, both male and female offspring were maintained on 100 ppb arsenic and fed either a normal (LFD) or high fat diet (HFD). At 10 and 24 weeks of age, the offspring were sacrificed and kidneys collected. Exposure to arsenic led to an increase body-weight in LFD diet-fed female but not male mice. This response was not observed in HFD-fed female mice; however male mice showed significant increases in body weight in both As- and non-treated animals. Histological analysis shows that arsenic exposure significantly increases HFD-induced glomerular area expansion, mesangial matrix accumulation and fibrosis compared to LFD control animals. HFD alone increases renal inflammation and fibrosis; reflected by increases in IL-1ß, ICAM-1 and fibronectin levels. Arsenic exposure significantly increases HFD-induced inflammatory and oxidative stress responses. In general, male mice have more severe responses than female mice to HFD or arsenic treatment. These results demonstrate that arsenic exposure causes sex-dependent alterations in HFD-induced kidney damage.


Assuntos
Arsênico/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Nefropatias/etiologia , Rim/efeitos dos fármacos , Animais , Arsênico/toxicidade , Peso Corporal/efeitos dos fármacos , Inflamação/etiologia , Rim/lesões , Nefropatias/induzido quimicamente , Nefropatias/patologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fatores Sexuais
15.
BMC Complement Altern Med ; 19(1): 117, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170991

RESUMO

BACKGROUND: Glossogyne tenuifolia (GT) is a traditional herbal tea in Penghu Island, Taiwan. Its extract is traditionally been used as an antipyretic, hepatoprotective and anti-inflammatory remedy in folk medicine among local residents. The present study investigated whether GT could improve streptozotocin-induced acute liver injury of type 2 diabetes mellitus. METHODS: Male Wistar rats aged eight weeks were induced to be hyperglycemic by the subcutaneous injection of streptozotocin-nicotinamide (STZ-NA) and a combination of a high-fat diet (HFD) (N group). The animals were given GT extracts at a low dose (50 mg/kg) (L group) or a high dose (150 mg/kg) (H group) or an anti-diabetic drug (acarbose) (P group) in drinking water for 4 weeks. RESULTS: The results revealed that STZ-NA increased hepatomegaly, hepatocyte cross-sectional area, hypertrophy-related pathways (IL6/STAT3-MEK5-ERK5, NFATc3, p38 and JNK MAPK), proapoptotic molecules (cytochrome C, cleaved caspase-3), and fibrosis-related pathways (FGF-2, pERK1/2). These pathway components were then expressed at lower levels in the L and H group when compared with the N group. The liver-protective effect of GT in STZ-NA-induced diabetic rats with hyperlipidemia was through an enhancement in the activation of the compensatory PI3K-Akt and Bcl2 survival-related pathway. CONCLUSION: The results demonstrate that the hot water extracts of GT efficiently ameliorates the STZ-NA-induced diabetes associated liver damage in rat models.


Assuntos
Asteraceae , Diabetes Mellitus Experimental/complicações , Falência Hepática Aguda/prevenção & controle , Fígado/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Animais , Dieta Hiperlipídica/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Falência Hepática Aguda/etiologia , Masculino , Niacinamida , Fitoterapia , Extratos Vegetais/farmacologia , Ratos Wistar , Estreptozocina
16.
J Agric Food Chem ; 67(26): 7325-7335, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31184120

RESUMO

Tea polyphenols (TP) possess the ability to regulate dyslipidemia and gut microbiota dysbiosis. However, the underlying mechanism is still elusive. The present study explored the intervention of TP on high fat diet induced metabolic disorders, gut microbiota dysbiosis in mice, and the underlying intestinal mechanism. As a result, TP significantly ameliorated hyperlipidemia, improved the expression levels of hepatic lipid metabolism genes, and modulated gut microbiota. The underlying mechanism was supposed to rely on the maintaining of intestinal redox state by TP. Intestinal redox related indicators were significantly correlated with the distribution of gut microbiota. An unidentified genus of Lachnospiraceae, Bacteroides, Alistipes, and Faecalibaculum were identified as the biomarkers for intestinal redox state. Importantly, different dosages of TP modulated intestinal redox state and gut microbiota in varied patterns, and an overdose intake attenuated the beneficial effects on gut health. Our findings offered novel insights into the mechanism of TP on intestinal homeostasis.


Assuntos
Camellia sinensis/química , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Intestinos/microbiologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Hiperlipidemias/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Chá
17.
Nat Commun ; 10(1): 2700, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221967

RESUMO

Pathological obesity can result from genetic predisposition, obesogenic diet, and circadian rhythm disruption. Obesity compromises function of muscle, which accounts for a majority of body mass. Behavioral intervention that can counteract obesity arising from genetic, diet or circadian disruption and can improve muscle function holds untapped potential to combat the obesity epidemic. Here we show that Drosophila melanogaster (fruit fly) subject to obesogenic challenges exhibits metabolic disease phenotypes in skeletal muscle; sarcomere disorganization, mitochondrial deformation, upregulation of Phospho-AKT level, aberrant intramuscular lipid infiltration, and insulin resistance. Imposing time-restricted feeding (TRF) paradigm in which flies were fed for 12 h during the day counteracts obesity-induced dysmetabolism and improves muscle performance by suppressing intramuscular fat deposits, Phospho-AKT level, mitochondrial aberrations, and markers of insulin resistance. Importantly, TRF was effective even in an irregular lighting schedule mimicking shiftwork. Hence, TRF is an effective dietary intervention for combating metabolic dysfunction arising from multiple causes.


Assuntos
Transtornos Cronobiológicos/dietoterapia , Jejum/fisiologia , Síndrome Metabólica/dietoterapia , Músculo Esquelético/fisiopatologia , Obesidade/dietoterapia , Animais , Animais Geneticamente Modificados , Transtornos Cronobiológicos/etiologia , Transtornos Cronobiológicos/fisiopatologia , Ritmo Circadiano/fisiologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Drosophila melanogaster , Metabolismo Energético/fisiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/patologia , Síndrome Metabólica/fisiopatologia , Músculo Esquelético/patologia , Obesidade/etiologia , Obesidade/patologia , Obesidade/fisiopatologia , Sarcômeros/patologia , Jornada de Trabalho em Turnos/efeitos adversos , Resultado do Tratamento
18.
Life Sci ; 232: 116603, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254587

RESUMO

AIMS: Although anabolic steroids (AS) and trans-fatty acids overload exerts systemic toxicity and are independent risk factors for metabolic and cardiovascular disorders, their interaction remains poorly understood. Thus, we investigated the impact of a diet rich in trans-fatty acids (HFD) combined with AS on glycemic control, lipid profile, adipose tissue, skeletal muscle and pancreas microstructure and expression of genes involved in energy metabolism. MAIN METHODS: Forty-eight C57BL/6 mice were randomized into 6 groups treated for 12 weeks with a standard diet (SD) or a diet rich in C18:1 trans-fatty isomers (HFD), alone or combined with 10 or 20 mg/kg testosterone cypionate (AS). KEY FINDINGS: Our results indicated that AS improved glycemic control, upregulated gene expression of Glut-4 and CPT-1 in skeletal muscle, FAS, ACC and UCP-1 in adipose tissue. AS also reduced total and LDL cholesterol in mice fed a SD. When combined with the HFD, AS was unable to induce microstructural adaptations in adipose tissue, pancreatic islets and ß-cells, but potentiated GCK and Glut-2 (pancreas) and Glut-4 and CPT-1 (skeletal muscle) upregulation. HFD plus AS also downregulated FAS and ACC gene expression in adipose tissue. Combined with HFD, AS increased triacylglycerol circulating levels, improved insulin sensitivity and glycemic control in mice. SIGNIFICANCE: Our findings indicated that HFD and AS can interact to modulates glycemic control and lipid profile by a mechanism potentially related with a reprogramming of genes expression in organs such as the pancreas, adipose tissue and skeletal muscle.


Assuntos
Congêneres da Testosterona/genética , Congêneres da Testosterona/metabolismo , Ácidos Graxos Trans/metabolismo , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/fisiologia , Feminino , Glucose/metabolismo , Carga Glicêmica/fisiologia , Resistência à Insulina/genética , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Pâncreas/metabolismo , Ácidos Graxos Trans/fisiologia
19.
Life Sci ; 228: 251-257, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31078545

RESUMO

AIMS: In addition to potentially progressing to either cirrhosis or hepatocellular carcinoma, non-alcoholic steatohepatitis (NASH) is currently the leading indication for liver transplantation. Nintedanib has been clinically used to treat idiopathic pulmonary fibrosis for many years, but its effects in an animal model of NASH have not been tested. The purpose of this study was to evaluate the effects of nintendanib on NASH in choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD)-fed mice. MAIN METHODS: Male C57BL/6 mice were fed a CDAHFD for 6 weeks to induce NASH with liver fibrosis, and they were administered nintedanib (60 mg/kg/day) or distilled water orally in the last 2 weeks of the feeding period. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride, and non-esterified fatty acids concentrations were measured. Serum cytokeratin 18 fragment (CK18) was detected using ELISA. Liver tissue sections from mice were stained with hematoxylin-eosin and Masson's trichrome to assess the level of steatohepatitis and fibrosis. KEY FINDINGS: CDAHFD-fed mice exhibited higher serum ALT, AST, and ALP levels compared with Control mice. A significant increase in the serum CK18 level was observed in the NASH group compared with the Control group. CDAHFD feeding also enhanced steatohepatitis and hepatic fibrosis pathological features, which were reduced after nintedanib treatment. SIGNIFICANCE: Nintedanib exerted anti-inflammatory and anti-fibrotic effects in CDAHFD-induced NASH mice.


Assuntos
Anti-Inflamatórios/uso terapêutico , Indóis/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Triglicerídeos/sangue
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