RESUMEN
The metabolic syndrome (MetS) is a clinical manifestation strongly associated with cardiovascular disease, the main cause of death worldwide. In view of this scenario, many therapeutic proposals have appeared in order to optimize the treatment of individuals with MetS, including the practice of exercise training (ET) and the consumption of okra (O). The aim of the present study was to evaluate the effect of O consumption and/or ET in animals with MetS. In all, 32 male Zucker rats (fa/fa) at 10 weeks old were randomly distributed into four groups of 8 animals each: MetS, MetS+O, MetS+ET and MetS+ET+O, and 8 lean Zucker rats (fa/ +) comprised the control group. Okra was administered by orogastric gavage 2x/day (morning and night, 100 mg/kg), 5 days/week, for 6 weeks. The ET was performed on a treadmill 1x/day (afternoon), 5 days/week, 60 min/day, in an intensity of 70% of maximal capacity, for the same days of O treatment. It was found that, O consumption alone was able to promote improved insulin sensitivity (MetS 93.93 ± 8.54 mg/dL vs. MetS+O 69.95 ± 18.7 mg/dL, p ≤ 0.05, d = 1.65, CI = 50.32 -89.58, triglyceride reduction (MetS 492.9 ± 97.8 mg/dL vs. MetS+O 334.9 ± 98.0 mg/dL, p ≤ 0.05, d = 1.61, CI = 193.2-398.7). In addition, it promoted a reduction in systolic blood pressure (MetS 149.0 ± 9.3 mmHg vs. MetS+O 132.0 ± 11.4 mmHg, p ≤ 0.05, d = 1.63, CI = 120-140), prevented an increase in cardiac collagen (MetS 12.60 ± 2.08% vs. MetS+O 7.52 ± 0.77%, p ≤ 0.05, d = 3.24, CI = 6.56-8.49). When associated with ET, the results were similar. Thus, we conclude that O consumption combined or not with aerobic ET can have a protective effect on the cardiac tissue of rats with MetS.
Asunto(s)
Abelmoschus , Resistencia a la Insulina , Síndrome Metabólico , Animales , Masculino , Ratas , Suplementos Dietéticos , Síndrome Metabólico/terapia , Ratas ZuckerRESUMEN
OBJECTIVES: Diabetes has been strongly associated with periodontal diseases. The periodontal ligament (PDL) has an abundant extracellular matrix (ECM). Lysyl oxidases (LOXs) are closely associated with various diseases caused by abnormal ECM functions, however, the role of LOXs in periodontal diseases induced by diabetes remains unclear. METHODOLOGY: In this study, 8-week-old Zucker diabetic fatty rats were used to establish a type 2 diabetes mellitus (T2DM) model. After 9 and 16 weeks, hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical staining were performed. RESULTS: After 9 weeks, loose collagen fibers were found in the interradicular area of the diabetic group, in opposition to the control group. There were no significant differences in LOX expression between the diabetic and control groups (p>0.05). However, after 16 weeks, the diabetic group presented a disordered arrangement of the PDL, showing decreased collagen content and significantly increased lysyl oxidase-like protein 3 (LOXL3) expression when compared with the control group (p<0.05). This suggests that LOXL3 plays a significant role in periodontal histopathological changes in diabetic rats. CONCLUSION: Our study showed elevated LOXL3 expression in the PDL of diabetic rats after 16 weeks, suggesting that LOXL3 may be involved in the occurrence and development of periodontal histopathological changes in diabetic rats. LOXL3 could be further used as an indicator for the early diagnosis of diabetic periodontitis in T2DM patients in clinical settings.
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Aminoácido Oxidorreductasas/metabolismo , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Enfermedades Periodontales , Animales , Colágeno , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Eosina Amarillenta-(YS)/metabolismo , Hematoxilina/metabolismo , Ligamento Periodontal/metabolismo , Periodoncio , Proteína-Lisina 6-Oxidasa/metabolismo , Ratas , Ratas ZuckerRESUMEN
Obesity is characterized by excessive fat accumulation. The Zucker rat displays genetic obesity due to a mutation in the leptin receptor gene; this model is of great interest because of its similarity to human obesity. Brain regions may be affected by obesity, but detailed information is lacking. In the present study, we analyzed the morphology of neurons in the hippocampal trisynaptic circuit as well as the spatial memory of obese Zucker rats. We performed two experiments. Each experiment contained two experimental groups: the control group (male Long Evans rats) and the study group (obese male Zucker rats). We monitored the body weights of all rats over 4 weeks. In the first experiment, we analyzed the morphology of hippocampal neurons. Under anesthesia, we measured the abdominal and hip circumferences and collected at least 1 ml of blood to assess serum glucose (GLU), triglyceride (TGC), and cholesterol (COL) concentrations. We perfused the brains of these rats with 0.9% saline solution, incubated the brains in Golgi-Cox solution, and subsequently evaluated the morphology of pyramidal neurons in the hippocampus (the CA1-CA3 regions) and the entorhinal cortex as well as the morphology of granule neurons in the dentate gyrus. In the second experiment, we assessed the spatial memory of animals with the Morris water maze. The Zucker rats had an obese phenotype, as indicated by their elevated body weight and increased abdominal and hip circumferences as well as elevated GLU, COL, and TGC concentrations. Analysis of neurons from the specified regions in obese male Zucker rats indicated reduced dendritic arborization and reduced dendritic spine density. In terms of spatial learning and memory, the obese Zucker rats exhibited intact spatial learning (i.e., of platform location) but deficits in spatial memory. These data provide evidence that obesity alters the morphology and function of hippocampal neurons.
Asunto(s)
Hipocampo , Memoria Espacial , Humanos , Masculino , Ratas , Animales , Memoria Espacial/fisiología , Ratas Zucker , Ratas Long-Evans , Neuronas/fisiología , Trastornos de la Memoria/etiología , Plasticidad Neuronal , ObesidadRESUMEN
The complications of Metabolic Syndrome (MetS) include kidney disease, and most dialysis patients are diagnosed with MetS. The benefit of exercise training (ET) for MetS treatment is already well defined in the literature, but the antidiabetic and antihyperlipidemic benefits of okra (O) have been discovered only recently. The aim of this study was to evaluate the effects of O and/or ET supplementation on renal function and histology; serum urea and creatinine value; inflammation (IL-6, IL-10, TNF-α) and oxidative stress in renal tissue. For this, 32 Zucker rats (fa/fa) were randomly separated into four groups of 8 animals each: Metabolic Syndrome (MetS), MetS + Okra (MetS + O), MetS + Exercise Training (MetS + ET), and MetS + Exercise Training and Okra (MetS + ET + O), and 8 Zucker lean (fa/+) rats comprised the Control group (CTL). Okra was administered by orogastric gavage 2x/day (morning and night, 100 mg/kg) and ET performed on the treadmill, at moderate intensity, 1h/day, 5x/week for 6 weeks. Although the renal function was not altered, the animals with MetS showed greater fibrotic deposition accompanied by a worse stage of renal injury, in addition to increased kidney weight. Although all interventions were beneficial in reducing fibrosis, only ET combined with O was able to improve the degree of renal tissue impairment. ET improved the anti-inflammatory status and reduced nitrite levels, but the combination of ET and O was more beneficial as regards catalase activity. Okra consumption alone did not promote changes in inflammatory cytokines and oxidative stress in the kidney. In conclusion, ET combined or not with O seems to be beneficial in preventing the progression of renal disease when renal function is not yet altered.
Asunto(s)
Abelmoschus , Enfermedades Renales , Síndrome Metabólico , Animales , Riñón/metabolismo , Enfermedades Renales/metabolismo , Enfermedades Renales/prevención & control , Síndrome Metabólico/complicaciones , Síndrome Metabólico/terapia , Estrés Oxidativo , Ratas , Ratas ZuckerRESUMEN
ZO-2 is a peripheral tight junction (TJ) protein whose silencing in renal epithelia induces cell hypertrophy. Here, we found that in ZO-2 KD MDCK cells, in compensatory renal hypertrophy triggered in rats by a unilateral nephrectomy and in liver steatosis of obese Zucker (OZ) rats, ZO-2 silencing is accompanied by the diminished activity of LATS, a kinase of the Hippo pathway, and the nuclear concentration of YAP, the final effector of this signaling route. ZO-2 appears to function as a scaffold for the Hippo pathway as it associates to LATS1. ZO-2 silencing in hypertrophic tissue is due to a diminished abundance of ZO-2 mRNA, and the Sp1 transcription factor is critical for ZO-2 transcription in renal cells. Treatment of OZ rats with metformin, an activator of AMPK that blocks JNK activity, augments ZO-2 and claudin-1 expression in the liver, reduces the paracellular permeability of hepatocytes, and serum bile acid content. Our results suggest that ZO-2 silencing is a common feature of hypertrophy, and that ZO-2 is a positive regulator of the Hippo pathway that regulates cell size. Moreover, our observations highlight the importance of AMPK, JNK, and ZO-2 as therapeutic targets for blood-bile barrier dysfunction.
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Proteínas Quinasas Activadas por AMP , Hígado Graso , Proteína de la Zonula Occludens-2/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Vía de Señalización Hippo , Hipertrofia , Ratas , Ratas Zucker , Proteínas de Uniones EstrechasRESUMEN
Aerobic training (AT) promotes several health benefits that may attenuate the progression of obesity associated diabetes. Since AT is an important nitric oxide (NO-) inducer mediating kidney-healthy phenotype, the present study is aimed at investigating the effects of AT on metabolic parameters, morphological, redox balance, inflammatory profile, and vasoactive peptides in the kidney of obese-diabetic Zucker rats receiving L-NAME (N(omega)-nitro-L-arginine methyl ester). Forty male Zucker rats (6 wk old) were assigned into four groups (n = 10, each): sedentary lean rats (CTL-Lean), sedentary obese rats (CTL-Obese), AT trained obese rats without blocking nitric oxide synthase (NOS) (Obese+AT), and obese-trained with NOS block (Obese+AT+L-NAME). AT groups ran 60 min in the maximal lactate steady state (MLSS), five days/wk/8 wk. Obese+AT rats improved glycemic homeostasis, SBP, aerobic capacity, renal mitochondria integrity, redox balance, inflammatory profile (e.g., TNF-α, CRP, IL-10, IL-4, and IL-17a), and molecules related to renal NO- metabolism (klotho/FGF23 axis, vasoactive peptides, renal histology, and reduced proteinuria). However, none of these positive outcomes were observed in CTL-Obese and Obese+AT+L-NAME (p < 0.0001) groups. Although Obese+AT+L-NAME lowered BP (compared with CTL-Obese; p < 0.0001), renal damage was observed after AT intervention. Furthermore, AT training under conditions of low NO- concentration increased signaling pathways associated with ACE-2/ANG1-7/MASr. We conclude that AT represents an important nonpharmacological intervention to improve kidney function in obese Zucker rats. However, these renal and metabolic benefits promoted by AT are dependent on NO- bioavailability and its underlying regulatory mechanisms.
Asunto(s)
Riñón/metabolismo , Óxido Nítrico/metabolismo , Obesidad/metabolismo , Condicionamiento Físico Animal , Transducción de Señal/efectos de los fármacos , Animales , Disponibilidad Biológica , Glucemia/metabolismo , Inhibidores Enzimáticos/farmacología , Masculino , Mitocondrias/metabolismo , Modelos Animales , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Oxidación-Reducción/efectos de los fármacos , Ratas , Ratas Zucker , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The ventromedial hypothalamic nucleus (VMH) is located in the tuberal region of the hypothalamus and is traditionally considered the satiety center. In obese Zucker rats, which express a mutation in the leptin receptor gene and exhibit obesity from the first weeks of life, the morphology of VMH neurons is unknown. In the present study, we found that the dendritic length of VMH neurons in obese Zucker rats was significantly shorter than that in Long Evans rats. This finding allows us to suggest that obese Zucker rats exhibit both neuronal metabolic alterations related to leptin and a reduction in the flow of information within the neuronal circuits in which the VMH nucleus participates to regulate foraging.
Asunto(s)
Dendritas/patología , Neuronas/patología , Obesidad/patología , Núcleo Hipotalámico Ventromedial/patología , Animales , Forma de la Célula/fisiología , Ratas , Ratas ZuckerRESUMEN
INTRODUCTION: Diabetic obese patients are susceptible to the development of cardiovascular disease, including hypertension and cardiac dysfunction culminating in diabetic cardiomyopathy (DC), which represents a life-threatening health problem with increased rates of morbidity and mortality. The aim of the study is to characterize the effects of a new benzofuran N-acylhydrazone compound, LASSBio-2090, on metabolic and cardiovascular alterations in Zucker diabetic fatty (ZDF) rats presenting DC. METHODS: Male non-diabetic lean Zucker rats (ZL) and ZDF rats treated with vehicle (dimethylsulfoxide) or LASSBio-2090 were used in this study. Metabolic parameters, cardiovascular function, left ventricle histology and inflammatory protein expression were analyzed in the experimental groups. RESULTS: LASSBio-2090 administration in ZDF rats reduced glucose levels to 85.0 ± 1.7 mg/dL (p < 0.05). LASSBio-2090 also lowered the cholesterol and triglyceride levels from 177.8 ± 31.2 to 104.8 ± 5.3 mg/dL and from 123.0 ± 11.4 to 90.9 ± 4.8 mg/dL, respectively, in obese diabetic rats (p < 0.05). LASSBio-2090 normalized plasma insulin, insulin sensitivity and endothelial function in aortas from diabetic animals (p < 0.05). It also enhanced systolic and diastolic left-ventricular function and reverted myocardial remodeling by blocking the threefold elevation of TNF-α levels in hearts from ZDF rats. CONCLUSION: LASSBio-2090 alleviates metabolic disturbance and cardiomyopathy in an obese and diabetic rat model, thus representing a novel strategy for the treatment of cardiovascular complications in obesity-associated type 2 diabetes mellitus.
Asunto(s)
Benzofuranos/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cardiomiopatías Diabéticas/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Animales , Benzofuranos/administración & dosificación , Benzofuranos/química , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatías Diabéticas/metabolismo , Inyecciones Intraperitoneales , Masculino , Estructura Molecular , Obesidad/metabolismo , Ratas , Ratas ZuckerRESUMEN
BACKGROUND: Several studies have proved that physical activity (PA) regulates energetic metabolism associated with mitochondrial dynamics through AMPK activation in healthy subjects. Obesity, a condition that induces oxidative stress, mitochondrial dysfunction, and low AMPK activity leads to mitochondrial fragmentation. However, few studies describe the effect of PA on mitochondrial dynamics regulation in obesity. AIM: The present study aimed to evaluate the effect of a single session of PA on mitochondrial dynamics regulation as well as its effect on mitochondrial function and organization in skeletal muscles of obese rats (Zucker fa/fa). MAIN METHODS: Male Zucker lean and Zucker fa/fa rats aged 12 to 13 weeks were divided into sedentary and subjected-to-PA (single session swimming) groups. Gastrocnemius muscle was dissected into isolated fibers, mitochondria, mRNA, and total proteins for their evaluation. KEY FINDINGS: The results showed that PA increased the Mfn-2 protein level in the lean and obese groups, whereas Drp1 levels decreased in the obese group. OMA1 protease levels increased in the lean group and decreased in the obese group. Additionally, AMPK analysis parameters (expression, protein level, and activity) did not increase in the obese group. These findings correlated with the partial restoration of mitochondrial function in the obese group, increasing the capacity to maintain the membrane potential after adding calcium as a stressor, and increasing the transversal organization level of the mitochondria analyzed in isolated fibers. SIGNIFICANCE: These results support the notion that obese rats subjected to PA maintain mitochondrial function through mitochondrial fusion activation by an AMPK-independent mechanism.
Asunto(s)
Mitocondrias/patología , Fibras Musculares Esqueléticas/patología , Obesidad/patología , Condicionamiento Físico Animal , Adenilato Quinasa/metabolismo , Animales , Biomarcadores/metabolismo , Citrato (si)-Sintasa/metabolismo , ADN Mitocondrial/metabolismo , Regulación de la Expresión Génica , Masculino , Potencial de la Membrana Mitocondrial , Dinámicas Mitocondriales , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Tamaño de los Órganos , Estrés Oxidativo , Fosforilación , Ratas ZuckerRESUMEN
11-Beta hydroxysteroid dehydrogenase type 1 (11ß-HSD1) regulates cortisol levels mainly in adipose, hepatic and brain tissues. There is a relationship between the high activity of this enzyme and the development of obesity and metabolic disorders. The inhibition of 11ß-HSD1 has been shown to attenuate the development of type 2 diabetes mellitus, insulin resistance, metabolic syndrome and other diseases mediated by excessive cortisol production. In this work, fifteen benzothiazole derivatives substituted with electron-withdrawing and electron-donating groups were designed to explore their affinity for 11ß-HSD1 using in silico methods. The results show that (E)-5-((benzo[d]thiazol-2-ylimino)(methylthio)methylamino)-2-hydroxybenzoic acid (C1) has good physicochemical properties and favorable interactions with 11ß-HSD1 through hydrogen bonding and hydrophobic interactions in the catalytic site formed by Y183, S170 and Y177. Furthermore, C1 was synthesized and evaluated in vitro and ex vivo using clobenzorex (CLX) as a reference drug in obese Zucker rats. The in vitro results showed that C1 was a better inhibitor of human 11ß-HSD1 than CLX. The ex vivo assay results demonstrated that C1 was capable of reducing 11ß-HSD1 overexpression in mesenteric adipose tissue. Therefore, C1 was able to decrease the activity and expression of 11ß-HSD1 better than CLX.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Benzotiazoles/química , Benzotiazoles/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Anfetaminas/farmacología , Animales , Benzotiazoles/farmacología , Dominio Catalítico/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inhibidores Enzimáticos/farmacología , Humanos , Enlace de Hidrógeno/efectos de los fármacos , Interacciones Hidrofóbicas e Hidrofílicas/efectos de los fármacos , Masculino , Simulación del Acoplamiento Molecular , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Ratas , Ratas ZuckerRESUMEN
An increase in intracellular Ca2+ concentration ([Ca2+]i) plays a key role in controlling endothelial functions; however, it is still unclear whether endothelial Ca2+ handling is altered by type 2 diabetes mellitus, which results in severe endothelial dysfunction. Herein, we analyzed for the first time the Ca2+ response to the physiological autacoid ATP in native aortic endothelium of obese Zucker diabetic fatty (OZDF) rats and their lean controls, which are termed LZDF rats. By loading the endothelial monolayer with the Ca2+-sensitive fluorophore, Fura-2/AM, we found that the endothelial Ca2+ response to 20 µM and 300 µM ATP exhibited a higher plateau, a larger area under the curve and prolonged duration in OZDF rats. The "Ca2+ add-back" protocol revealed no difference in the inositol-1,4,5-trisphosphate-releasable endoplasmic reticulum (ER) Ca2+ pool, while store-operated Ca2+ entry was surprisingly down-regulated in OZDF aortae. Pharmacological manipulation disclosed that sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) activity was down-regulated by reactive oxygen species in native aortic endothelium of OZDF rats, thereby exaggerating the Ca2+ response to high agonist concentrations. These findings shed new light on the mechanisms by which type 2 diabetes mellitus may cause endothelial dysfunction by remodeling the intracellular Ca2+ toolkit.
Asunto(s)
Aorta/metabolismo , Calcio/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Endotelio Vascular/metabolismo , Animales , Señalización del Calcio/fisiología , Diabetes Mellitus Experimental , Modelos Animales de Enfermedad , Retículo Endoplásmico/metabolismo , Fura-2/análogos & derivados , Prueba de Tolerancia a la Glucosa , Homeostasis , Resistencia a la Insulina , Masculino , ATPasas Transportadoras de Calcio de la Membrana Plasmática/metabolismo , Ratas , Ratas Zucker , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Intercambiador de Sodio-Calcio/metabolismoRESUMEN
OBJECTIVE: To evaluate the effects of aerobic exercise training (AET) on cardiac miRNA-16 levels and its target gene VEGF related to microvascular rarefaction in obese Zucker rats (OZR). METHODS: OZR (n = 11) and lean (L; n = 10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT). Swimming exercise training lasted 60 min, 1×/day/10 weeks, with 4% body weight workload. Cardiac angiogenesis was assessed by histological analysis (periodic acid-Schiff) by calculating the capillary/fiber ratio. The protein expressions of VEGF, VEGFR2, and CD31 were evaluated by western blot. The expression of miRNA-16 was evaluated by real-time PCR. RESULTS: Heart rate decreased in the trained groups compared to sedentary groups. The cardiac capillary/fiber ratio was reduced in OZR compared to L, LT and OZRT groups, indicating that aerobic exercise training (AET) was capable of reversing the microvascular rarefaction in the obese animals. miRNA-16 expression was increased in OZR compared to L, LT and OZRT. In contrast, its target, VEGF protein expression was 24% lower in OZR compared to L group, which has been normalized in OZRT group. VEGFR2 protein expression was increased in trained groups compared to their controls. CD31, a endothelial cells marker, showed increased expression in OZRT compared to OZR, indicating greater vascularization in OZRT group. CONCLUSION: AET induced cardiac angiogenesis in obese animals. This revascularization is associated with a decrease in miRNA-16 expression permissive for increased VEGF protein expression, suggesting a mechanism for potential therapeutic application in vascular diseases.
Asunto(s)
Vasos Coronarios/patología , MicroARNs/genética , Rarefacción Microvascular/prevención & control , Miocardio/metabolismo , Obesidad/terapia , Condicionamiento Físico Animal , Animales , Masculino , MicroARNs/metabolismo , Rarefacción Microvascular/genética , Actividad Motora/fisiología , Revascularización Miocárdica , Neovascularización Fisiológica/genética , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad/fisiopatología , Condicionamiento Físico Animal/métodos , Ratas , Ratas Zucker , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
We previously reported that aerobic exercise training (AET) consisted of 10 weeks of 60-min swimming sessions, and 5 days/week AET counteracts CH in obesity. Here, we evaluated the role of microRNAs and their target genes that are involved in heart collagen deposition and calcium signaling, as well as the cardiac remodeling induced by AET in obese Zucker rats. Among the four experimental Zucker groups: control lean rats (LZR), control obese rats (OZR), trained lean rats (LZR + TR), and trained obese rats (OZR + TR), heart weight was greater in the OZR than in the LZR group due to increased cardiac intramuscular fat and collagen. AET seems to exert a protective role in normalizing the heart weight in the OZR + TR group. Cardiac microRNA-29c expression was decreased in OZR compared with the LZR group, paralleled by an increase in the collagen volumetric fraction (CVF). MicroRNA-1 expression was upregulated while the expression of its target gene NCX1 was decreased in OZR compared with the LZR group. Interestingly, AET restored cardiac microRNA-1 to nonpathological levels in the OZR-TR group. Our findings suggest that AET could be used as a nonpharmacological therapy for the reversal of pathological cardiac remodeling and cardiac dysfunction in obesity.
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Corazón/fisiopatología , MicroARNs/metabolismo , Obesidad/genética , Obesidad/terapia , Condicionamiento Físico Animal/fisiología , Animales , Masculino , Obesidad/patología , Obesidad/fisiopatología , Ratas , Ratas ZuckerRESUMEN
Sterculia apetala (order: Malvales, family: Sterculiaceae) seed oil contains two cyclopropene fatty acids: sterculic and malvalic acid. Both positive and negative effects have been associated with the consumption of sterculic oil. In Mexico, S. apetala seeds are consumed after being boiled or roasted, used as chocolate flavoring, and utilized as animal fodder. Therefore, it is important to evaluate whether the consumption of this seed has a negative impact on the organism. The aim of this study was to evaluate the effect of administration of sterculic oil, during an 8-week period, on anxiety-like behavior and spontaneous locomotor activity in Zucker rats, analyzed through light/dark and open-field tests. The results showed that the consumption of sterculic oil decreased exploration latency in light/dark tests, which suggests an anxiolytic-like effect. Alterations in time spent on rearing and grooming were present in open-field tests, but this was not statistically significant, discarding nonspecific motor alterations. The alterations found in this study are possibly related to intrinsic obesity and metabolic complications present in the Zucker rat model, where leptin plays an important role in animal mood, more so than sterculic oil consumption.
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Ansiolíticos/administración & dosificación , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Aceites de Plantas/administración & dosificación , Sterculia/química , Animales , Ansiolíticos/química , Ansiedad/etiología , Conducta Animal/efectos de los fármacos , Humanos , Masculino , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/psicología , Aceites de Plantas/química , Ratas , Ratas Zucker , Semillas/químicaRESUMEN
SCOPE: Hyperglucagonemia contributes to hyperglycemia in type 2 diabetes (T2D). Previously, we have found that soy protein normalized fasting hyperglucagonemia in obese Zucker (fa/fa) rats, sensitizing the HSL-lipolytic signaling pathway in white adipose tissue (WAT), however the mechanism remains unknown. METHODS AND RESULTS: Zucker (fa/fa) rats were fed casein or soy protein diet in combination with soybean or coconut oil. Glucagon receptor (GR) was increased at the plasma membrane of adipocytes of rats fed soy protein compared to those fed casein, without changes in total GR abundance. The protein abundance of Rab4, a GTPase involved in GR fast recycling, was dramatically up-regulated in adipocytes of rats fed soy protein. The proportion of GR bound to Rab4 or to RAMP2, involved in promoting GR ligand-binding and G protein selectivity, increased when soy protein was combined with soybean oil as fat source. In rats fed soy protein with coconut oil, Rab11 levels, a protein involved in the slow recycling of GR, was also increased. CONCLUSION: Soy protein increases GR recycling to the membrane of adipocytes and its ligand-binding and G protein selectivity, suggesting, it could be used in T2D dietary treatment to reestablish glucagon sensitivity in WAT, leading to the regulation of circulating glucagon levels.
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Adipocitos/efectos de los fármacos , Glucagón/sangre , Obesidad/sangre , Receptores de Glucagón/metabolismo , Proteínas de Soja/farmacología , Adipocitos/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Animales , Membrana Celular/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dieta , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Hiperglucemia/sangre , Hiperglucemia/tratamiento farmacológico , Masculino , Obesidad/tratamiento farmacológico , Ratas , Ratas Zucker , Receptores de Glucagón/genética , Triglicéridos/sangre , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismoRESUMEN
Background. We investigated the effects of exercise training (ET) on miR-126 levels and skeletal muscle angiogenesis in obese Zucker rats. Results. Zucker rats were randomly assigned to sedentary and swimming-trained groups: lean sedentary (LS) and trained (LTR); obese sedentary (OB) and trained (OBTR). The OB group displayed capillary rarefaction compared with the LS group. In contrast, ET increased the capillary/fiber ratio by 38% in the LTR group and normalized capillary rarefaction in the OBTR group. VEGF, PI3K, and eNOS levels were reduced in the skeletal muscle of the OB group. ET normalized VEGF, PI3K, and eNOS levels in OBTR, contributing to vascular network homeostasis. PI3KR2 inhibits PI3K, a key mediator of the VEGF signaling pathway. Obesity decreased miR-126 and increased PI3KR2 levels compared with the LS group. However, ET normalized miR-126 levels in the OBTR group versus the LS group and decreased expression of PI3KR2. Conclusion. Our findings show that obesity leads to skeletal muscle capillary rarefaction, which is regulated by decreased miR-126 levels and increased PI3KR2. Inversely, ET normalizes miR-126 levels and VEGF signaling and should be considered an important therapeutic strategy for vascular disorders.
Asunto(s)
Capilares/fisiología , MicroARNs/metabolismo , Músculo Esquelético/metabolismo , Animales , Composición Corporal/fisiología , Citrato (si)-Sintasa/metabolismo , Regulación hacia Abajo , Masculino , Músculo Esquelético/enzimología , Neovascularización Fisiológica , Óxido Nítrico Sintasa de Tipo III/metabolismo , Obesidad/metabolismo , Obesidad/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Ratas , Ratas Zucker , Transducción de Señal , Natación , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Oxidative stress and nitrosative stress present in type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) induce inflammatory response in diverse tissues including cavernous tissue (CT). Heat-shock proteins (HSPs) have an important role in modulating and repairing tissue injury, although their participation in CT in T2DM is unclear. Beyond the specific action of phosphodiesterase type 5 inhibitors (PDE5i) on erectile function, it has been proposed that chronic administration of these agents improves endothelial function and ameliorates fibrotic changes. The aim of this study was to determine in CT of Zucker Diabetic Fatty (ZDF) rat, an experimental model of T2DM and MS: (1) the degree of oxidative stress and nitrosative stress; (2) the magnitude of inflammatory markers such as tumor necrosis factor-α (TNFα) and interleukin 6 (IL6); (3) immunoexpression of HSP70 and HSP27; (4) how a long-term PDE5i administration may modify these variables. For 6 months, (1) untreated ZDF; (2) ZDF+Sildenafil (Sil) and (3) control Lean Zucker Rat (LZR) received no treatment, were studied. Penises were processed for functional 'in vitro' studies, oxidative and nitrosative stress evaluation and immunohistochemistry in CT using TNFα; IL6; nitrotyrosine, HSP70 and HSP27 antibodies. ZDF+Sil presented better relaxation in corporal strips versus untreated ZDF. Furthermore, ZDF+Sil presented less lipoperoxidation in CT versus untreated ZDF. The activity of antioxidant enzymes CuZn superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPx) was also reduced in untreated ZDF in CT along with a decrease in glutathione versus untreated ZDF. Nitrotyrosine expression was increased in untreated-ZDF rats versus ZDF+Sil and LZR. TNFα and IL6 were decreased in CT in ZDF+Sil versus untreated ZDF. Additionally, the expression of HSP70 and HSP27 was reduced in CT in ZDF+Sil versus untreated ZDF. In conclusion, this study provides substantial evidence supporting a protective role of a long-term therapy with Sil on CT in a recognized animal model of T2DM and MS.
Asunto(s)
Proteínas de Choque Térmico/metabolismo , Inflamación/metabolismo , Pene/efectos de los fármacos , Inhibidores de Fosfodiesterasa 5/farmacología , Animales , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Pene/metabolismo , Ratas , Ratas ZuckerRESUMEN
The purpose of this research was to describe the pharmacokinetic parameters of ß-hydroxyphosphocarnitine (ß-HPC; CAS No. 1220955-20-3) after a single oral dose in rats and rabbits as well as to assess the impact of 14 weeks of ß-HPC (100 mg/kg) treatment on the serum metabolites and liver enzymes, body weight, and hepatic steatosis of lean and obese Zucker fa/fa rats. In the case of the rat and rabbit study, the ß-HPC area under the curve, biological half-life, and clearance were 2,174.4 versus 3,128 µg â h/ml, 23.7 versus 8.87 h, and 13.9 versus 151.1 ml/h in the rats versus the rabbits, respectively. The values for the time of maximal concentration were 0.58 versus 1.53 h, for the maximal concentration, they were 62.4 versus 221.4 µg/ml, and for the absorption rate constant 0.02 versus 2.40 h(-1), respectively. In the case of the Zucker fa/fa rat study, ß-HPC administered orally once a day reduced insulin, triglyceride, and cholesterol levels in the liver and serum; it also reduced weight gain and decreased liver steatosis in obese rats after 14 weeks. ß-HPC could therefore potentially be used in the treatment of metabolic syndrome.
Asunto(s)
Carnitina/análogos & derivados , Hígado Graso/prevención & control , Síndrome Metabólico/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Organofosfatos/farmacología , Administración Oral , Animales , Área Bajo la Curva , Carnitina/farmacocinética , Carnitina/farmacología , Colesterol/metabolismo , Hígado Graso/etiología , Hígado Graso/patología , Semivida , Insulina/metabolismo , Masculino , Obesidad/complicaciones , Organofosfatos/farmacocinética , Conejos , Ratas , Ratas Wistar , Ratas Zucker , Especificidad de la Especie , Triglicéridos/metabolismo , Aumento de Peso/efectos de los fármacosRESUMEN
This study aimed to identify the aerobic capacity enhancement and subsequent body weight (BW) status of obese Zucker rats (OZRs) after 4 weeks of treadmill running exercise at the maximal lactate steady state (MLSS). In addition to obese Zucker rats (OZRs), lean Wistar Kyoto rats (WKYs) were used, and both species were divided into control and exercise groups as follows: obese exercise (OZR-EX, n=5), obese control (OZR-CON, n=5), lean exercise (WKY-EX, n=5) and lean control (WKY-CON, n=5). The OZR and WKY exercise groups trained 5 days per week at 12.5 m.min-1 and 20 m.min-1, respectively. After 4 weeks of training, MLSS was ascertained to evaluate the animals' aerobic capacity using 3 different velocities (12.5, 15 and 17.5 m.min-1 for OZRs and 25, 30 and 35 m.min-1 for WKYs). The MLSS of OZR-EX was identified at the velocity of 15 m.min-1, representing a 20% increase in aerobic capacity after the exercise program. The MLSS of WKY-EX was identified at 30 m.min-1 with a 50% increase of in aerobic capacity. Obese animals that exercised showed reduced weight gain compared to the non-exercise obese control group (p <0.05). Our results thus show that exercise training at MLSS intensity increased the aerobic capacity in both obese and non-obese animals and also reduced BW gain.
Asunto(s)
Terapia por Ejercicio , Obesidad/terapia , Condicionamiento Físico Animal , Aumento de Peso , Animales , Modelos Animales de Enfermedad , Femenino , Ácido Láctico/sangre , Masculino , Obesidad/sangre , Obesidad/fisiopatología , Consumo de Oxígeno , Ratas , Ratas Endogámicas WKY , Ratas ZuckerRESUMEN
Obesity has been considered a public health issue in many countries and is of increasing concern for authorities over the past 6 years. The Zucker rat is a good experimental model for obesity and diabetes studies due to its metabolic characteristics that are similar to those developed by humans. A total of 12 obese Zucker rats and their lean littermates were killed in pubertal and young adult phases for assessing organ weights (testis and epididymis), testicular histomorphometric and stereological analyses, daily sperm production, and transit time in the epididymis. Sperm integrity was also investigated in the adult animals using the Comet assay. Alterations in organ weights, seminiferous epithelium architecture, sperm production, and transit time were noticed in the pubertal fatty rats. The volume density of the lymphatic space was decreased in both the ages. Adult animals had a significant increase in the extent of damage found in sperm DNA. Our results show for the first time that leptin receptor deficiency compromises sperm production during puberty and that genetic obese Zucker rats have increased sperm DNA fragmentation.