Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice.

SummaryHypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons

Liver-specific activation of AMPK prevents steatosis on a high fructose diet

AMP-activated protein kinase (AMPK) plays a key role in integrating metabolic pathways in response to energy demand. We identified a mutation in the γ1 subunit (γ1D316A) that leads to activation of AMPK. We generated mice with this mutation to study the effect of chronic liver-specific activation of AMPK in vivo. Primary hepatocytes isolated from these mice have reduced gluconeogenesis and fatty acid synthesis, but there is no effect on fatty acid oxidation compared to cells from wild-type mice. Liver-specific activation of AMPK decreases lipogenesis in vivo and completely protects against hepatic steatosis when mice are fed a high-fructose diet. Our findings demonstrate that liver-specific activation of AMPK is sufficient to protect against hepatic triglyceride accumulation, a hallmark of non-alcoholic fatty liver disease (NAFLD). These results emphasize the clinical relevance of activating AMPK in the liver to combat NAFLD and potentially other associated complications (e.g., cirrhosis and hepatocellular carcinoma)

Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice.

SummaryHypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons

AMPK activation protects against diet induced obesity through Ucp1-independent thermogenesis in subcutaneous white adipose tissue

Obesity results from a chronic imbalance between energy intake and energy output but remains difficult to prevent or treat in humans. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an important regulator of energy homeostasis1,2,3 and is a molecular target of drugs used for the treatment of metabolic diseases, including obesity4,5. Here we show that mice expressing a gain-of-function AMPK mutant6 display a change in morphology of subcutaneous white adipocytes that is reminiscent of browning. However, despite a dramatic increase in mitochondrial content, Ucp1 expression is undetectable in these adipocytes. In response to a high-fat diet (HFD), expression of skeletal muscle–associated genes is induced in subcutaneous white adipocytes from the gain-of-function AMPK mutant mice. Chronic genetic AMPK activation results in protection against diet-induced obesity due to an increase in whole-body energy expenditure, most probably because of a substantial increase in the oxygen consumption rate of white adipose tissue. These results suggest that AMPK activation enriches, or leads to the emergence of, a population of subcutaneous white adipocytes that produce heat via Ucp1-independent uncoupling of adenosine triphosphate (ATP) production on a HFD. Our findings indicate that AMPK activation specifically in adipose tissue may have therapeutic potential for the treatment of obesity

Practical nutritional recovery strategies for elite soccer players when limited time separates repeated matches

Specific guidelines that aim to facilitate the recovery of soccer players from the demands of training and a congested fixture schedule are lacking; especially in relation to evidence-based nutritional recommendations. The importance of repeated high level performance and injury avoidance while addressing the challenges of fixture scheduling, travel to away venues, and training commitments requires a strategic and practically feasible method of implementing specific nutritional strategies. Here we present evidence-based guidelines regarding nutritional recovery strategies within the context of soccer. An emphasis is placed on providing practically applicable guidelines for facilitation of recovery when multiple matches are played within a short period of time (i.e. 48 h). Following match-play, the restoration of liver and muscle glycogen stores (via consumption of ~1.2 gkg-1h-1 of carbohydrate) and augmentation of protein synthesis (via ~40 g of protein) should be prioritised in the first 20 minutes of recovery. Daily intakes of 6-10 gkg-1 body mass of carbohydrate are recommended when limited time separates repeated matches while daily protein intakes of >1.5 gkg-1 body mass should be targeted; possibly in the form of multiple smaller feedings (e.g., 6 x 20-40 g). At least 150% of the body mass lost during exercise should be consumed within 1 h and electrolytes added such that fluid losses are ameliorated. Strategic use of protein, leucine, creatine, polyphenols and omega-3 supplements could also offer practical means of enhancing post-match recovery. Keywords: soccer, nutrition, recovery, polyphenols, omega-3, creatine, fixture, congestio

Olanzapine-Induced Hyperphagia and Weight Gain Associate with Orexigenic Hypothalamic Neuropeptide Signaling without Concomitant AMPK Phosphorylation

The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance

Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress

Purpose High-fructose consumption and chronic stress are both associated with metabolic inflammation and insulin resistance. Recently, disturbed activity of energy sensor AMP-activated protein kinase (AMPK) was recognized as mediator between nutrient-induced stress and inflammation. Thus, we analyzed the effects of high-fructose diet, alone or in combination with chronic stress, on glucose homeostasis, inflammation and expression of energy sensing proteins in the rat liver. Methods In male Wistar rats exposed to 9-week 20% fructose diet and/or 4-week chronic unpredictable stress we measured plasma and hepatic corticosterone level, indicators of glucose homeostasis and lipid metabolism, hepatic inflammation (pro- and anti-inflammatory cytokine levels, Toll-like receptor 4, NLRP3, activation of NF kappa B, JNK and ERK pathways) and levels of energy-sensing proteins AMPK, SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha). Results High-fructose diet led to glucose intolerance, activation of NF kappa B and JNK pathways and increased intrahepatic IL-1 beta, TNF alpha and inhibitory phosphorylation of insulin receptor substrate 1 on Ser(307). It also decreased phospho-AMPK/AMPK ratio and increased SIRT1 expression. Stress alone increased plasma and hepatic corticosterone but did not influence glucose tolerance, nor hepatic inflammatory or energy-sensing proteins. After the combined treatment, hepatic corticosterone was increased, glucose tolerance remained preserved, while hepatic inflammation was partially prevented despite decreased AMPK activity. Conclusion High-fructose diet resulted in glucose intolerance, hepatic inflammation, decreased AMPK activity and reduced insulin sensitivity. Chronic stress alone did not exert such effects, but when applied together with high-fructose diet it could partially prevent fructose-induced inflammation, presumably due to increased hepatic glucocorticoids

A discursive review of the textual use of ‘trapped’ in environmental migration studies: The conceptual birth and troubled teenage years of trapped populations

First mooted in 2011, the concept of Trapped Populations referring to people unable to move from environmentally high-risk areas broadened the study of human responses to environmental change. While a seemingly straightforward concept, the underlying discourses around the reasons for being ‘trapped’, and the language describing the concept have profound influences on the way in which policy and practice approaches the needs of populations at risk from environmental stresses and shocks. In this article, we apply a Critical Discourse Analysis to the academic literature on the subject to reveal some of the assumptions implicit within discussing ‘trapped’ populations. The analysis reveals a dominant school of thought that assisted migration, relocation, and resettlement in the face of climate change are potentially effective adaptation strategies along a gradient of migrant agency and governance

Identificación de equipos y procedimientos utilizados por fisioterapeutas brasileños para pruebas de endurance muscular inspiratoria

A avaliação da função dos músculos inspiratórios por meio do teste de endurance muscular inspiratória (EMI), definida como a capacidade de sustentação dessa tarefa ao longo do tempo, atualmente apresenta ampla variedade de instrumentos e procedimentos para sua mensuração. Este estudo teve como objetivo identificar os diferentes equipamentos, procedimentos e forma de avaliação dos testes de EMI entre fisioterapeutas brasileiros. É um estudo transversal realizado por meio de questionário enviado por correio eletrônico individualmente a cada participante. Cento e treze fisioterapeutas de diferentes regiões do país, grande parte com atuação conjunta na clínica e na docência (52,1%), responderam realizar poucas vezes a medida de EMI (48,7%). O manovacuômetro aneroide foi o aparelho mais utilizado por 42,5% dos profissionais. O clipe nasal e o bocal tubular de plástico rígido ou papel foram os acessórios mais utilizados durante o teste, correspondendo a 51,8% e 33%, respectivamente. O teste de ventilação voluntária máxima foi o mais utilizado para avaliação da endurance inspiratória, relatado por 23% dos respondentes. O teste de carga constante para avaliação da endurance foi adotado por 51,2% dos fisioterapeutas, sendo que 54,9% associaram comandos verbais à demonstração para explicação do teste. A interpretação dos valores aferidos era feita através de valores de referência por 25,7% dos entrevistados. Identificou-se que os fisioterapeutas brasileiros entrevistados não apresentaram a mesma conduta para os testes de EMI. No entanto os equipamentos, procedimentos e a forma de avaliação são utilizados com base nas diretrizes sobre o tema e de acordo com a disponibilidade de recursos do serviço.La evaluación de la función de los músculos inspiratorios a través del entrenamiento muscular inspiratorio (EMI), definida como la capacidad de sustentación de esta tarea a lo largo del tiempo, actualmente presenta una amplia variedad de instrumentos y procedimientos para su medición. Este estudio tuvo como objetivo identificar los diferentes equipos, procedimientos y forma de evaluación de las pruebas de EMI entre fisioterapeutas brasileños. Es un estudio transversal realizado por medio de un cuestionario enviado por correo electrónico a cada participante. Ciento trece fisioterapeutas de diferentes regiones del país, que en gran parte actúan a la vez en la clínica y en la enseñanza (52,1%), dijeron realizar pocas veces la medida de EMI (48,7%). El manovacuómetro aneroide fue el aparato más utilizado por el 42,5% de los profesionales. El clip nasal y la boquilla tubular de plástico rígido o papel fueron los accesorios más utilizados durante la prueba, correspondiendo al 51,8% y al 33%, respectivamente. La prueba de ventilación voluntaria máxima fue la más utilizada para la evaluación de la resistencia respiratoria, reportada por el 23% de los entrevistados. La prueba de carga constante para la evaluación de la resistencia se adoptó por el 51,2% de los fisioterapeutas, siendo que el 54,9% asoció comandos verbales a la demostración para la explicación de la prueba. La interpretación de los valores evaluados se hacía a través de valores de referencia por el 25,7% de los entrevistados. Se identificó que los fisioterapeutas brasileños entrevistados no presentaron la misma conducta para las pruebas de EMI. Sin embargo, los equipos, procedimientos y la forma de evaluación se utilizan con base en las directrices sobre el tema y de acuerdo con la disponibilidad de recursos del servicio.The assessment of inspiratory muscles through the inspiratory muscle endurance test (IME), defined as the ability to support this task over time, currently presents wide range of instruments and procedures for its measurement. This study aimed to identify the different equipment, procedures and assessments of IME tests among Brazilian physical therapists. It is a cross-sectional study carried out through a questionnaire sent individually by electronic mail to each participant. One hundred and thirteen physical therapists from different regions of the country, many practicing in the clinic and in the teaching field (52.1%), said they measured IME a few times (48.7%). The aneroid manovacuometer was used by 42.5% of the professionals. The nose clip and the hard plastic or paper tubular incentive spirometer were the most used accessories during the test, corresponding to 51.8% and 33%, respectively. The maximum voluntary ventilation test was used to assess the inspiratory endurance, reported by 23% of the respondents. The constant load test for endurance assessment was adopted by 51.2% of the physical therapists, and 54.9% associated verbal commands with the demonstration for the test application. The interpretation of the measured values was made with reference values by 25.7% of respondents. We identified that Brazilian physical therapists interviewed did not show the same conduct for IME tests. However, the equipment, procedures and assessment form are used based on the guidelines on the subject and according to the availability of resources of the service