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@#Introduction: Rice bran oil (RBO) is used in Asian countries as a daily dietary supplement. RBO is known in particular for its hypolipidemic effect. There has been increasing interest recently in the use of RBO as a means to maintain body weight and prevent obesity, though the mechanism of how this happens is still not well understood. We have investigated the effect of RBO on expression of genes that might influence energy homeostasis and feed intake. Methods: This study assessed Sprague-Dawley male rats at 12-weeks that were split into three groups over a 28-day period. A control group was fed a diet of standard rat chow, a standard group was fed standard rat chow with Orlistat (10.8 mg/kg bw/day), and a treatment group was fed standard rat chow with RBO (57.6 mg oryzanol/day). All supplementation was given by oral gavage. Possible adiposity was investigated through a histological analysis of adipocytes size measurement of intra-abdominal white adipose tissue in the rats. Changes in gene expression in the liver were determined by microarray. Results: The data suggest that RBO supplementation of a regular diet did not result in excess body weight and adiposity. A microarray analysis of the rats’ livers found that RBO altered the expression of genes related to energy homeostasis and feeding behavior, by upregulating genes such as Olr522, RGD1561231 and Rgs16. Conclusion: It is suggested that RBO supplementation can be used to maintain body weight by lowering appetite.
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Brain aging is an inevitable process characterized by structural and functional changes and is a major risk factor for neurodegenerative diseases. Most brain aging studies are focused on neurons and less on astrocytes which are the most abundant cells in the brain known to be in charge of various functions including the maintenance of brain physical formation, ion homeostasis, and secretion of various extracellular matrix proteins. Altered mitochondrial dynamics, defective mitophagy or mitochondrial damages are causative factors of mitochondrial dysfunction, which is linked to age-related disorders. Etoposide is an anti-cancer reagent which can induce DNA stress and cellular senescence of cancer cell lines. In this study, we investigated whether etoposide induces senescence and functional alterations in cultured rat astrocytes. Senescence-associated β-galactosidase (SA-β-gal) activity was used as a cellular senescence marker. The results indicated that etoposide-treated astrocytes showed cellular senescence phenotypes including increased SA-β-gal-positive cells number, increased nuclear size and increased senescence-associated secretory phenotypes (SASP) such as IL-6. We also observed a decreased expression of cell cycle markers, including Phospho-Histone H3/Histone H3 and CDK2, and dysregulation of cellular functions based on wound-healing, neuronal protection, and phagocytosis assays. Finally, mitochondrial dysfunction was noted through the determination of mitochondrial membrane potential using tetramethylrhodamine methyl ester (TMRM) and the measurement of mitochondrial oxygen consumption rate (OCR). These data suggest that etoposide can induce cellular senescence and mitochondrial dysfunction in astrocytes which may have implications in brain aging and neurodegenerative conditions.
Subject(s)
Animals , Rats , Aging , Astrocytes , Brain , Cellular Senescence , Cell Cycle , Cell Line , DNA , Etoposide , Extracellular Matrix Proteins , Homeostasis , Interleukin-6 , Membrane Potential, Mitochondrial , Mitochondria , Mitophagy , Mitochondrial Dynamics , Neurodegenerative Diseases , Neurons , Neuroprotection , Oxygen Consumption , Phagocytosis , Phenotype , Risk Factors , Wound HealingABSTRACT
La obesidad es una enfermedad crónica caracterizada por un aumento patológico de grasa corporal generado por un desbalance entre los ingresos y los egresos energéticos; este exceso de energía se almacena en el tejido adiposo, el cual no solo almacena lípidos, sino que secreta numerosas hormonas, por lo que constituye el órgano endocrino de mayor tamaño del organismo. A diferencia de otras glándulas endocrinas, su masa es variable y puede aumentar o disminuir progresivamente de tamaño dependiendo de la edad, la ingesta alimentaria, la actividad física, la programación perinatal y la predisposición genética; se destaca dentro de los factores secretados la leptina, la cual participa en la regulación del balance energético y la secreción de gonadotropinas.El objetivo de la presente revisión bibliográfica es describir el papel de la leptina como señal aferente en la regulación de la homeostasis energética, y se destaca su importancia como uno de los mecanismos implicados en la patogénesis de la obesidad.
Obesity is a chronic disease characterized by a pathological rise of body fat generated by an imbalance between energy input and output. This energy excess is stored in the adipose tissue which not only stores lipids but also secretes numerous hormones and represents the biggest endocrine organ of the human body. Unlike other endocrine glands, it has a variable mass and may gradually increase or decrease its size depending on age, food intake, physical activity, perinatal scheduling and genetic predisposition. Among the secreted factors are leptin which participates in the regulation of energy balance and the gonadotropin secretions. The objective of this literature review was to describe the role of leptin as afferent signal in the regulation of energy homeostasis; its importance as one of the mechanisms involved in obesity pathogenesis was underlined.
Subject(s)
Humans , Leptin , Leptin/physiology , Homeostasis/physiologyABSTRACT
[Summary] Kisspeptin is vital for the neuroendocrine regulation of GnRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GnRH neurons. A number of metabolic modulators have been proposed as regulators of kisspeptin including leptin, adiponectin, insulin, ghrelin, POMC, and neuropeptide Y. Recent data indicate that kisspeptin may have a direct role in regulating energy balance by its regulation of food intake and glucose homeostasis. Thus, kisspeptin may serve as a new connection between reproductive function and energy metabolism.
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The neuronal and hormonal regulations of food intake expand our knowledge about energy balance .The cen-tral nervous system integrates endocrine signals to regulate food intake and energy consumption .The nervous system and endo-crine system interact with each other to regulate feeding behavior .This paper was a review of the neuronal and endocrine regu-lation of food intake ,and offered a revealing insight for the study and treatment of metabolic disorders .
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Neste estudo, foram incluídos 201 indivíduos com idade de 30 a 80 anos, sendo 100 obesos (IMC> 30 kg/m2) e 101 indivíduos do grupo controle. Os obesos participaram do programa de orientação nutricional para redução do peso corporal. As medidas antropométricas, avaliação da composição corporal e o perfil metabólico foram avaliados no grupo total. Os polimorfismos genéticos foram analisados pela técnica de PCR em tempo real e apenas o polimorfismo do gene IL 6 por PCR convencional. A avaliação de consumo alimentar foi realizada em apenas 73 indivíduos obesos que completaram o programa de orientação nutricional. Não encontramos associação entre os polimorfismos estudados e a obesidade em nosso estudo. No polimorfismo LEP -2548G>A, os indivíduos do grupo controle apresentaram concentração elevada de VLDL-c e triglicérides. Para o polimorfismo LEP 19A>G, os indivíduos obesos apresentaram concentração elevada de VLDL-c, insulina, HDL-c e valores aumentados de Homaß e o grupo controle apresentou a concentração elevada de hemoglobina glicada. Para o polimorfismo LEPR Lys109Arg (c.326A>G), os obesos apresentaram valores aumentados de CA e RCQ e concentração elevada de ApoB e HDL-c, enquanto que os indivíduos do grupo controle apresentaram os valores aumentados de IMC, CA e teor de gordura e usPCR. Para o polimorfismo Gln223Arg (c.668A>G), os obesos apresentaram valores aumentados de teor de gordura e a concentração elevada de hemoglobina glicada e usPCR . Os indivíduos obesos, para o polimorfismo ADIPOQ 45T>G, apresentaram as concentrações elevadas de colesterol total e LDL-c ao passo que no grupo controle as concentrações elevadas de glicose e triglicérides. Para o polimorfismo 276G>T, os obesos apresentaram valores aumentados de IMC, CA, RCQ e teor de gordura e concentração elevada de IL-6. Os mesmos indivíduos apresentaram também o valor de IMC aumentado e a concentração de usPCR elevada para o polimorfismo PPARG Pro12Ala (34G>C). Já para o polimorfismo 161C>T os indivíduos obesos demosntraram a concentração elevada de HDL-c enquanto o grupo controle apresentou a concentração elevada de insulina e IL-1ß. Os indivíduos obesos para o polimorfismo IL-6 -174 G>C, apresentaram os valores de CA aumentados e a concentração elevada de PAI-1 já para os indivíduos do grupo controle a concentração elevada de ApoA, IL1ß e usPCR. No programa intervencional, foi possível observarmos uma adequação em relação ao consumo recomendado de carboidrato e lipídios, excedendo apenas proteínas. O consumo de carboidratos foi maior nos grupos com graus II e III de obesidade. Após a intervenção nutricional, observamos mudanças no hábito alimentar dos envolvidos devido à diminuição da ingestão calórica e á redução do perfil lipídico, inflamatório, nos polimorfismos LEP, LEPR, ADIPOQ, PPARG e IL6. Os indivíduos obesos portadores dos haplótipos TG+GG/GG, para os polimorfismos do gene ADIPOQ, apresentaram valor aumentado de CA, RCQ e concentração elevada de glicose. Os portadores do haplótipo TG+GG/GT+TT demonstraram hemoglobina glicada e ApoB. Os indivíduos obesos portadores dos haplótipos AG+GG/GG, para os polimorfismos do gene LEPR, apresentaram valores aumentados de CA, RCQ e teor de gordura, já portadores do haplótipo AG+GG/AG+GG demonstraram concentração elevada de leptina, adiponectina, glicose, usPCR e HDL-c
This study included 201 individuals aged 30 to 80 years, and 100 obese (BMI> 30 kg/m2) and 101 control subjects. The obese participated in the program of nutritional guidelines for weight reduction. Anthropometric measurements, assessment of body composition and metabolic profile were evaluated in the total group. The genetic polymorphisms were analyzed by PCR in real time and only the IL 6 gene polymorphism by conventional PCR. The assessment of food intake was performed in only 73 obese subjects who completed the program of nutrition education. We found no association between the studied polymorphisms and obesity in our study. Polymorphism in the LEP-2548G> A, the control subjects showed high concentration of VLDL-C and triglycerides. For LEP polymorphism 19A> G, obese individuals showed high concentration of VLDL-C, insulin, HDL-C and increased values of Homaß and the control group had a high concentration of glycated hemoglobin. To LEPR polymorphism Lys109Arg (c.326A> G), obese patients presented increased values of WC and WHR and high concentration of ApoB and HDL-c, while those in the control group showed increased values of BMI, WC and content values of fat and high concentration of usPCR. To polymorphism Gln223Arg (c.668A> G), obese patients presented increased values of fat content and high concentration of glycated hemoglobin and usPCR. Obese people, for the ADIPOQ polymorphism 45T> G, showed elevated concentrations of total cholesterol and LDL-C while in the control group the concentrations of glucose and triglycerides. For the polymorphism 276G> T, the obese had increased values of BMI, WC, WHR and fat content and high concentration of IL-6. The same individuals also had increased the value of BMI and the concentration of high usPCR for the PPARg polymorphism Pro12Ala (34G> C).As for the polymorphism 161 C> T obese individuals demonstrated the high concentration of HDL-C while the control group had a high concentration of insulin and IL-1ß. Obese individuals for polymorphism IL-6 -174 G> C showed increased values of WC and the high concentration of PAI-1 as for individuals in the control group, the high concentration of ApoA, and IL1ß usPCR. In the interventional program was able to observe a suitability in relation to recommended intake of carbohydrates and lipids, exceeding only protein. The carbohydrate intake was higher in groups II and III degree of obesity. After nutritional intervention, we observed changes in dietary habits of those involved due to decreased caloric intake and reducing the lipid profile, inflammatory, polymorphisms in the LEP, LEPR, ADIPOQ, PPARg and IL6. Obese individuals carring the haplotype TG+GG/GG, for the polymorphisms ADIPOQ gene showed increased values of WC, WHR end elevated glucose. Carries of haplotype TG+GG/GT showed glycate hemoglobin and ApoB. Obese individuals carrying the haplotype GG + AG / GG for the LEPR gene polymorphisms showed increased values of WC, WHR and fat, as carriers of the haplotype AG+GG/AG+GG showed high concentration of leptin, glucose, HDL-c and us PCR
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Polymorphism, Genetic , Weight Loss , Homeostasis , Insulin/administration & dosage , Obesity , Haplotypes , Nutrition Assessment , Diet, Reducing , Metabolic Diseases , Molecular BiologyABSTRACT
La grelina es una hormona peptídica secretada principalmente por el estómago. Fue descrita inicialmente como un factor estimulador de la secreción de hormona de crecimiento. Sin embargo pronto se descubrió que también juega un papel importante en la regulación del comportamiento alimentario tanto en animales como en humanos; la grelina estimula el apetito y por lo tanto está implicada en el control del balance energético y peso corporal. La regulación anormal de los niveles de grelina conduce tanto a sobre peso como a bajo peso. Adicionalmente, parece ser que la eficacia de las diferentes estrategias utilizadas en el control del peso corporal depende en parte en su capacidad de modificar los niveles plasmáticos de grelina. Mientras que los efectos de la grelina han sido relativamente bien documentados, los mecanismos responsables de sus efectos están siendo continuamente investigados y actualizados. Como consecuencia de esto, actualmente se están comenzando a desarrollar una serie de aplicaciones clínicas para los agonistas y antagonistas grelinérgicos El propósito de esta revisión es proveer información actualizada sobre el mecanismo de acción y papel de la grelina en regulación de la ingesta alimentaria y el balance energético. También se discutirá brevemente el papel de dicha hormona como blanco potencial de drogas para el tratamiento de la obesidad y caquexia.
Ghrelin is a peptide hormone secreted by the stomach. It was initially described as a stimulant of growth hormone secretion. Soon, however, it was discovered to play an important role in feeding behaviour in animals and in appetite regulation in man: ghrelin stimulates appetite, and as such is an orexigenic peptide implicated in energy balance mechanisms and weight gain. Abnormal ghrelin activity leads to over- or underweight. Additionally, the efficacy of different treatment strategies against obesity seems to be related to modifications in plasma ghrelin levels. Whereas the effects of ghrelin in the regulation of appetite, food intake and energy homeostasis have been fairly well documented, the pathways responsible for the effects of ghrelin are now increasingly being understood. As a consequence, clinical applications of ghrelin are now being developed. The purpose of this review is to provide updated information on the role of ghrelin in food intake and energy homeostasis, and on its mechanism of action. Moreover, the potential of ghrelin as a target for drugs to treat cachexia and obesity will be discussed.
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New insights in the complex metabolic pathways and its control mechanism for energy homeostasis have refined our understanding of the pathophysiology of obesity. It is now recognized that there are several additional regulatory mechanism such as peripheral signals including leptin, ghrelin, GLP-1 and PYY and cellular signals including uncoupling proteins and beta Adrenergic receptors, which contribute to the regulation of food intake and energy expenditure, respectively. In addition, the function of adipocyte as an endocrine organ in energy homeostasis has been recently emphasized. Recent findings suggest that elevated levels of adipokines, such as leptin, adiponectin, resistin and TNF-alpha, in addition to increased free fatty acid level could be related to the pathophysiology of insulin resistance in obesity. For effective treatments and prevention of obesity, further studies on the circuits of neural and endocrine interactions in the regulation of energy homeostasis are needed.
Subject(s)
Adipocytes , Adipokines , Adiponectin , Eating , Energy Metabolism , Ghrelin , Glucagon-Like Peptide 1 , Homeostasis , Insulin Resistance , Leptin , Metabolic Networks and Pathways , Obesity , Receptors, Adrenergic, beta , Resistin , Tumor Necrosis Factor-alphaABSTRACT
Adipose tissue is an important endocrine regulator of glucose metabolism and energy homeostasis. Researches have focused on this tissue not only as a target for pharmacotherapy of obesity and insulin resistance but also as an endocrine tissue with leptin secretion and high insulin sensitivity. Brown adipose tissue (BAT) additionally plays a unique role in thermoregulation through the mitochondrial uncoupling protein 1 (UCP1), which uncouples oxidative phosphorylation. As a genetic tissue ablation model of BAT, we made transgenic mice expressing herpes simplex virus thymidine kinase (HSV-TK) driven by the brown adipocyte- specific UCP1 minimal regulatory element. The HSV-TK transgene was expressed specifically in BAT and more than 35% increase of apoptosis was induced by ganciclovir (GCV) treatment. Nevertheless, the expression level was not high enough to induce BAT ablation in GCV-treated adult mice. Importantly, however, we found that brown adipocytes in the periphery of interscapular BAT were transformed into white adipocyte-like unilocular cells. These cells express white adipocyte-specific leptin protein but are different in the ultrastructure of mitochondria from classical white adipocytes. Our data indicates that atrophy of BAT causes transformation into white adipocyte-like cells in the adult mouse and also suggests that further molecular understanding of adipocyte plasticity using our transgenic mouse model might be beneficial for the development of anti-obesity/anti-diabetic therapies.