Hypothalamic S1p/s1pr1 axis controls energy homeostasis

Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats5485

Hypothalamic S1p/s1pr1 Axis Controls Energy Homeostasis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.5Capes-12900-13-3; CAPES; Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Schwartz, M.W., Woods, S.C., Porte, D., Jr., Seeley, R.J., Baskin, D.G., Central nervous system control of food intake (2000) Nature, 404, pp. 661-671Munzberg, H., Huo, L., Nillni, E.A., Hollenberg, A.N., Bjorbaek, C., Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin (2003) Endocrinology, 144, pp. 2121-2131Myers, M.G., Cowley, M.A., Munzberg, H., Mechanisms of leptin action and leptin resistance (2008) Annu. Rev. 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Brain Regulation Of Food Intake And Expenditure Energy: Molecular Action Of Insulin, Leptin And Physical Exercise [regulación Central De La Ingestión Alimentaria Y El Gasto Energético: Acciones Moleculares De La Insulina, La Leptina Y El Ejercicio Físico]

Introduction. Overweight and obesity present significant public health concerns because of the link with numerous chronic health conditions. During the last ten years, since the discovery of leptin, great advances were obtained in the characterization oh the hypothalamic mechanisms involved in the control of food intake and thermogenesis. Development. This review will present some the most recent findings in this field. It will be focused on the actions of leptin and insulin in the hypothalamus and will explore the hypothesis that hypothalamic resistance to the action of these hormones may play a key role in the development of obesity. Conclusions. The physical activity is an important component on long-term weight control. The exercise markedly increased phosphorylation activity of several proteins involved in leptin and insulin signal transduction in the hypothalamus. 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Effects Of Physical Exercise In The Ampkα Expression And Activity In High-fat Diet Induced Obese Rats [efeitos Do Exercício Físico Na Expressão E Atividade Da Ampkα Em Ratos Obesos Induzidos Por Dieta Rica Em Gordura]

Introduction: High-fat diet is a special risk factor in the development of insulin resistance and type 2 diabetes. Objective: To investigate the effects of physical exercise on the AMPK expression and activity in high-fat diet induced obese rats. Methods: Wistar rats were randomly divided into four groups and received either a rat maintenance diet (control group) or an isocaloric high-fat diet (HFD) (sedentary groups and exercised groups) for four months. Two different exercise protocols were utilized: Acute or chronic swimming exercise. Insulin tolerance test was performed to estimate whole-body insulin sensitivity. AMPKα and GLUT4 as well as pAMPKα and pACC of rats' skeletal muscle levels were determined using Western blot. Results: Insulin tolerance test revealed a significantly impaired insulin action after HFDt feeding, indicating high-fat induced insulin resistance when compared to control group. Four months of HFD treatment induced to significant decrease of AMPKα (2.2-fold) and GLUT4 (2.5-fold) protein contents and also of p-AMPKα (2.4-fold) and p-ACC (2.5-fold) in sedentary rats' skeletal muscle when compared with the control group. Both exercise protocols resulted in increase of AMPKα and ACC phosphorylation and increase in insulin sensitivity, while chronic physical exercise alone provoked increase in these proteins expression (p < 0.05). 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The Role Of Neuronal Ampk As A Mediator Of Nutritional Regulation Of Food Intake And Energy Homeostasis

Hypothalamic 5′-adenosine monophosphate-activated protein kinase (AMPK) senses intracellular metabolic stress, i.e., an increase in the cellular AMP:ATP ratio, and integrates diverse hormonal and nutritional signals to restore energy balance. Recent evidence suggests that different nutrients can modulate AMPK activity in the hypothalamus, thereby controlling weight gain through a leptin-independent mechanism. Understanding the mechanisms by which nutrients control hypothalamic AMPK activity is crucial to the development of effective nutritional interventions for the treatment of food intake-related disorders, such as anorexia and obesity. 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New Mechanisms By Which Physical Exercise Improves Insulin Resistance In The Skeletal Muscle [novos Mecanismos Pelos Quais O Exercício Físico Melhora A Resistência à Insulina No Músculo Esquelético]

Insulin resistance of skeletal muscle glucose transport is a key-defect for the development of impaired glucose tolerance and type 2 diabetes. However, it is known that both an acute bout of exercise and chronic endurance exercise training can bring beneficial effects on insulin action in insulin-resistant states. However, little is currently known about the molecular effects of acute exercise on muscle insulin signaling in the post-exercise state in insulin-resistant organisms. 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Analysis Of The Physical Activity Effects And Measurement Of Pro-inflammatory Cytokines In Irradiated Lungs In Rats [análise Dos Efeitos Da Atividade Física E Mensuração De Citocinas Pró-inflamatórias Em Pulmões Irradiados Em Ratos]

PURPOSE: To study if the pre-radiotherapy physical activity has radio-protective elements, by measuring the radio-induced activation of pro-inflammatory cytokines as interleukin-6 (il-6), transforming growth factor -β (tgf -β), tumor necrosis factor -α (tnf-α) and protein beta kinase β (ikkβ), through western blotting analysis. METHODS: A randomized study with 28 Wistar hannover rats, males, with a mean age of 90 days and weighing about 200 grams. The animals were divided into three groups: (GI, GII and GIII). GIII group were submitted to swimming for eight weeks (zero load, three times a week, about 30 minutes). Then, the groups (except the control group) were submitted to irradiation by cobalt therapy, single dose of 3.5 gray in the whole body. All animals were sacrificed by overdose of pentobarbital, according to the time for analysis of cytokines, and then a fragment of the lower lobe of the right lung went to western blotting analysis. RESULTS: The cytokines IKK β, TNF-α and IL-6 induced by radiation in the lung were lower in the exercised animals. However, exercise did not alter the radiation-induced increase in tgf-β. 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