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OBJECTIVE To estimate seroprevalence of SARS-CoV-2 antibodies in schoolchildren aged 4 to 14 years living in the city of São Paulo, according to clinical, demographic, epidemiological, and social variables, during the school closure period as a measure against covid-19 spread. METHODS A serological survey was made in September 2020 with a random sample stratified by school system (municipal public, state public and private) type. A venous blood sample was collected using the Wondfo SARS-CoV-2 Antibody Test (lateral flow method) for detection of total SARS-CoV-2 virus antibodies. Semi-structured questionnaires were applied to collect clinical, demographic, social, and epidemiological data. RESULTS Seroprevalence of SARS-CoV-2 antibodies in schoolchildren was of 16.6% (95%CI 15.4–17.8). The study found higher seroprevalence in the municipal (18.5%; 95%CI 16.6–20.6) and state (16.2%; 95%CI 14.4–18.2) public school systems compared to the private school system (11.7; 95%CI 10.0–13.7), among black and brown students (18.4%; 95%CI 16.8–20.2) and in the most vulnerable social stratum (18.5 %;95%CI 16.9–20.2). Lower seroprevalence was identified in schoolchildren who reported following the recommended protective measures against covid-19. CONCLUSION Seroprevalence of SARS-CoV-2 antibodies is found mainly in the most socially vulnerable schoolchildren. This study can contribute to support public policies that reinforce the importance of suspending face-to-face classes and developing strategies aimed at protective measures and monitoring of the serological status of those who have not yet been included in the vaccination schedule. RESUMO OBJETIVO Estimar a soroprevalência de anticorpos do vírus SARS-CoV-2 em escolares de quatro a 14 anos de idade residentes no município de São Paulo, segundo variáveis clínicas, demográficas, epidemiológicas e sociais, durante o período de fechamento das escolas como medida de controle da covid-19. MÉTODOS Realizou-se um inquérito sorológico em setembro de 2020 com amostra aleatória estratificada por tipo de rede de ensino (pública municipal, pública estadual e privada). Foi coletada amostra de sangue venoso utilizando-se o teste de imunoensaio de fluxo lateral da fabricante Wondfo para detecção de anticorpos totais contra o vírus SARS-CoV-2. Aplicaram-se questionários semiestruturados para o levantamento de dados clínicos, demográficos, sociais e epidemiológicos. RESULTADOS A soroprevalência de anticorpos do vírus SARS-CoV-2 em escolares foi de 16,6% (IC95% 15,4–17,8). O estudo encontrou soroprevalências mais elevadas na rede pública municipal (18,5%; IC95% 16,6–20,6) e estadual (16,2%; IC95% 14,4–18,2) em relação à rede privada (11,7; IC95% 10,0–13,7) e entre escolares da raça/cor preta e parda (18,4%; IC95% 16,8–20,2) e no estrato social mais vulnerável (18,5%; IC95% 16,9–20,2). A pesquisa identificou menores soroprevalências nos escolares que relataram seguir as medidas recomendadas de proteção contra a covid-19. CONCLUSÃO A soroprevalência de anticorpos contra o vírus SARS-CoV-2 atinge principalmente os escolares socialmente mais vulneráveis. Este estudo pode contribuir para embasar políticas públicas que reforcem a importância da suspensão das aulas presenciais e da necessidade de estratégias de medidas de proteção e acompanhamento do status sorológico daqueles que ainda não foram contemplados no calendário vacinal.

Cells display complex intracellular organization by compartmentalization of metabolic processes into organelles, yet the resolution of these structures in the native tissue context and their functional consequences are not well understood. Here we resolved the three-dimensional structural organization of organelles in large (more than 2.8×105µm3) volumes of intact liver tissue (15 partial or full hepatocytes per condition) at high resolution (8nm isotropic pixel size) using enhanced focused ion beam scanning electron microscopy1,2 imaging followed by deep-learning-based automated image segmentation and 3D reconstruction. We also performed a comparative analysis of subcellular structures in liver tissue of lean and obese mice and found substantial alterations, particularly in hepatic endoplasmic reticulum (ER), which undergoes massive structural reorganization characterized by marked disorganization of stacks of ER sheets3 and predominance of ER tubules. Finally, we demonstrated the functional importance of these structural changes by monitoring the effects of experimental recovery of the subcellular organization on cellular and systemic metabolism. We conclude that the hepatic subcellular organization ofthe ER architecture are highly dynamic, integrated with the metabolic state and critical for adaptive homeostasis and tissue health.

Mitochondrial reactive oxygen species (mROS) are central to physiology. While excess mROS production has been associated with several disease states, its precise sources, regulation, and mechanism of generationin vivoremain unknown, limiting translational efforts. Here we show that in obesity, hepatic ubiquinone (Q) synthesis is impaired, which raises the QH2/Q ratio, driving excessive mROS production via reverse electron transport (RET) from site IQin complex I. Using multiple complementary genetic and pharmacological modelsin vivowe demonstrated that RET is critical for metabolic health. In patients with steatosis, the hepatic Q biosynthetic program is also suppressed, and the QH2/Q ratio positively correlates with disease severity. Our data identify a highly selective mechanism for pathological mROS production in obesity, which can be targeted to protect metabolic homeostasis.

The endoplasmic reticulum (ER) is a key organelle involved in the regulation of lipid and glucose metabolism, proteostasis, Ca

O objetivo desta pesquisa foi determinar a incidência e analisar o perfil dos portadores de lesão por pressão, enfocando fatores de risco, caracterí­sticas clí­nicas e demográficas dos pacientes internados em Unidade de Terapia Intensiva (UTI) do hospital IMIP, assim como estádio e localização das lesões no corpo. Trata-se de um estudo descritivo, documental, com abordagem quantitativa. Realizado na UTI Cirúrgica do complexo hospitalar do Instituto de Medicina Integral Professor Fernando Figueira (IMIP), localizado em Recife no estado de Pernambuco, através da coleta de dados dos censos diários e do uso da escala de Braden com um formulário especí­fico durante o perí­odo de outubro de 2018 a dezembro de 2018. Percebe-se a importância de um trabalho em equipe, com planejamento estratégico, buscando sempre solucionar as falhas não de forma isolada, mas em conjunto, seja na área médica, da enfermagem, nutricional, fisioterapia, e dos outros profissionais envolvimentos no cuidado do paciente internado nesta unidade.

Inhibiting IP 3 Rs in adipocytes may prevent the development of obesity-induced metabolic complications.

Chronic metabolic inflammation is a key feature of obesity, insulin resistance, and diabetes. Here, we showed that altered regulation of the Ca(2+) channel inositol trisphosphate receptor (IP3R) was an adipocyte-intrinsic event involved in the emergence and propagation of inflammatory signaling and the resulting insulin resistance. Inflammation induced by cytokine exposure in vitro or by obesity in vivo led to increases in the abundance and activity of IP3Rs and in the phosphorylation of the Ca(2+)-dependent kinase CaMKII in adipocytes in a manner dependent on the kinase JNK. In mice, adipocyte-specific loss of IP3R1/2 protected against adipose tissue inflammation and insulin resistance, despite the mice exhibiting substantial diet-induced weight gain. Thus, this work suggests that increased IP3R activity is a key link between obesity, inflammation, and insulin resistance. These data also suggest that approaches to target IP3R-mediated Ca(2+) homeostasis in adipocytes may offer new therapeutic opportunities against metabolic diseases, especially because GWAS studies also implicate this locus in human obesity.

Objective: to analyze whether trombonists present orofacial myofunctional changes and compare the electrical activity of the orbicularis oris muscle before and after playing their instrument. Methods: an observational, descriptive, and cross-sectional study. The sample consisted of 20 university trombonists. Data collection involved three steps: application of a questionnaire investigating some peculiarities of trombonists (Orofacial Myofunctional Evaluation with Expanded Scores - OMES-E), and electromyographic analysis of the orbicularis oris muscle before and after performing a piece with the trombone. The mean, standard deviation, frequency, and percentage were calculated, and the paired Student’s t test was used to compare the means of the electromyographic records before and after playing the trombone, at a 5% significance. Results: seventy per cent of trombonists reported some symptom of orofacial myofunctional alteration, namely, muscle compensations, tension, and pain. The myofunctional evaluation showed a mild change in cheek volume (90%) and labial commissure asymmetry (60%). The electrical activity of the lower orbicularis oris muscle decreased significantly after the trombone practice (p = 0.04), while that of the superior orbicularis oris muscle remained unchanged. Conclusion:trombonists show clinical and self-reported oromyofunctional changes as well as decreased electrical activity of the lower orbicularis oris muscle, after playing the trombone. RESUMO Objetivos: analisar se existem alterações miofuncionais orofaciais clínicas e autorreferidas em trombonistas, assim como comparar a atividade elétrica do músculo orbicular da boca antes e após o uso do trombone. Métodos: estudo transversal e observacional, cuja amostra foi composta por 20 universitários trombonistas. Foi utilizado um questionário que investiga algumas particularidades sobre o instrumentista, da Avaliação Miofuncional Orofacial Com Escores Ampliados - AMIOFE-A e análise eletromiográfica do músculo orbicular da boca antes e após execução de uma tarefa com o trombone. Foram calculadas: média, desvio padrão, frequência e porcentagem e utilizou-se o teste t-Student pareado na comparação das médias dos registros eletromiográficos pré e pós-execução do trombone, significância=5%. Resultados: setenta por centro dos trombonistas relataram algum sintoma de alteração miofuncional orofacial, sendo compensações musculares, tensão e dor. Na avaliação miofuncional encontrou-se alteração leve no volume de bochechas (90%) e comissuras labiais com assimetria (60%). Houve redução significante da atividade elétrica do músculo orbicular inferior após a execução de tarefa com trombone (p=0,04), enquanto a do superior permaneceu inalterada. Conclusão: trombonistas apresentam alterações oromiofuncionais clínicas e autorreferidas e diminuição da atividade elétrica do músculo orbicular inferior da boca após uso do trombone.

Cells display complex intracellular organization through compartmentalization of metabolic processes into organelles, yet neither the resolution of these structures in the native tissue context nor its functional consequences are well understood. Here, we resolved the 3-dimensional organelle structural organization in large (>2.8×105μm3) volumes of intact liver tissue (15 partial or full hepatocytes per condition) in high resolution (8nm isotropic pixel size) by utilizing enhanced Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) imaging, followed by deep-learning-based image segmentation and 3D reconstruction. We also performed a comparative analysis of subcellular structures in liver tissue of lean and obese animals and found marked alterations particularly in hepatic endoplasmic reticulum (ER), which undergoes massive structural re-organization in obesity characterized by marked disorganization of stacks of ER sheets and predominance of ER tubules. Finally, we demonstrated the functional importance of these structural changes upon experimental recovery of the subcellular organization and its marked impact on cellular and systemic metabolism. We conclude that hepatic subcellular organization and ER’s architecture is highly dynamic, integrated with the metabolic state, and critical for adaptive homeostasis and tissue health.

SummaryChronic metabolic inflammation is a key feature of obesity, insulin resistance and diabetes, although the initiation and propagation mechanisms of metaflammation are not fully established, particularly in the adipose tissue. Here we show that in adipocytes, altered regulation of the Ca2+ channel inositol triphosphate receptor (IP3Rs) is a key, adipocyte-intrinsic, event involved in the emergence and propagation of inflammatory signaling and the resulting insulin resistance. Inflammation, either induced by cytokine exposure in vitro or by obesity in vivo lead to increased expression and activity of IP3Rs in adipocytes in a JNK-dependent manner. This results in increased cytosolic Ca2+ and impaired insulin action. In mice, adipocyte-specific loss of IP3R1/2 protected against adipose tissue inflammation and insulin resistance despite significant diet-induced weight gain. Thus, this work reveals that IP3R over-activation and the resulting increase in cytosolic Ca2+ is a key link between obesity, inflammation and insulin resistance, and suggests that approaches to target adipocyte Ca2+ homeostasis may offer new therapeutic opportunities against metabolic diseases, especially since GWAS studies also implicate this locus in human obesity.

Adipocytes possess remarkable adaptive capacity to respond to nutrient excess, fasting or cold exposure, and they are thus an important cell type for the maintenance of proper metabolic health. Although the endoplasmic reticulum (ER) is a critical organelle for cellular homeostasis, the mechanisms that mediate adaptation of the ER to metabolic challenges in adipocytes are unclear. Here we show that brown adipose tissue (BAT) thermogenic function requires an adaptive increase in proteasomal activity to secure cellular protein quality control, and we identify the ER-localized transcription factor nuclear factor erythroid 2-like 1 (Nfe2l1, also known as Nrf1) as a critical driver of this process. We show that cold adaptation induces Nrf1 in BAT to increase proteasomal activity and that this is crucial for maintaining ER homeostasis and cellular integrity, specifically when the cells are in a state of high thermogenic activity. In mice, under thermogenic conditions, brown-adipocyte-specific deletion of Nfe2l1 (Nrf1) resulted in ER stress, tissue inflammation, markedly diminished mitochondrial function and whitening of the BAT. In mouse models of both genetic and dietary obesity, stimulation of proteasomal activity by exogenously expressing Nrf1 or by treatment with the proteasome activator PA28α in BAT resulted in improved insulin sensitivity. In conclusion, Nrf1 emerges as a novel guardian of brown adipocyte function, providing increased proteometabolic quality control for adapting to cold or to obesity.

Objective: to compare the electrical activity of masseter muscles, bilaterally, according to the presence or absence of Temporomandibular Disorder (TMD) in college students with a high degree of anxiety. Methods: the study was conducted with a randomized sample of 31 Speech Therapy students aged between 17 and 32 years; 61.3% (n = 19) were females and 38.7% (n = 12) were males. They were divided into two groups, Group 1 (G1), comprising 11 students with TMD, and Group 2 (G2), composed of 20 students without TMD. The college students answered the State-Trait Anxiety Inventory (STAI) for anxiety investigation, and were evaluated by the protocol Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) for TMD diagnosis. The evaluation of muscular electrical activity took into account the records in the conditions of rest, Sustained Maximum Voluntary Activity (SMVA) and habitual chewing (HC). The data were analyzed using the version 22 IBM Statistical Package for Social Sciences (SPSS) software. The statistical analysis was performed using Student t test to compare means between groups, considering < 0,05 as the significant p-value. Results: college students, of both groups, presented high levels of anxiety traits. Significant statistical differences were observed on the percentage of electrical activity of right masseter muscle in chewing function, as well as muscle fibers recruitment during chewing, which were higher on the group without TMD. Conclusion: college students with TMD and a high degree of anxiety presented lower means of masseter muscle electromyografic activity during chewing, in most conditions assessed, as compared to volunteers without TMD, except for the left masseter muscle in rest and chewing. RESUMO Objetivo: comparar a atividade elétrica dos músculos masseteres bilateralmente de acordo com a presença ou ausência de Disfunção Temporomandibular (TMD) em estudantes universitários com alto grau de ansiedade. Métodos: o estudo foi realizado com 31 acadêmicos de Fonoaudiologia, selecionados aleatoriamente, com idades entre 17 e 32 anos, sendo 61,3% (n=19) do sexo feminino e 38,7% (n=12) do sexo masculino, divididos em dois grupos, sendo o Grupo 1 (G1) composto por 11 estudantes com DTM e o Grupo 2 (G2) formado por 20 estudantes sem DTM. Para investigação da ansiedade os estudantes universitários responderam o Inventário de Ansiedade Traço-Estado (IDATE), e para o diagnóstico de DTM, foram avaliados por meio do protocolo Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). A avaliação da atividade elétrica muscular considerou os registros nas condições de repouso, Máxima Atividade Voluntária Sustentada (MAVS) e mastigação habitual (MH). Os dados foram analisados por meio do software IBM Statistical Package for Social Sciences (SPSS), versão 22. A estatística analítica foi realizada por meio do teste T de Student para comparação das médias entre os grupos. Os dados foram considerados significantes, quando o p-valor fosse inferior a 5%. Resultados: os graduandos, de ambos os grupos, apresentaram alto nível de ansiedade traço. Foram verificadas diferenças estatisticamente significantes para a porcentagem da atividade elétrica do músculo masseter direito na mastigação, bem como no recrutamento de fibras musculares na mastigação, as quais foram superiores no grupo sem DTM. Conclusões: universitários com DTM e alto grau de ansiedade apresentaram médias de atividade eletromiográfica do músculo masseter inferiores as do grupo sem DTM, na maioria das condições avaliadas, exceto para o masseter esquerdo em repouso e na mastigação.

Endoplasmic reticulum stress (ERS) has a pathophysiological role in obesity-associated insulin resistance. Yet, the coordinated tissue response to ERS remains unclear. Increased connexin 43 (Cx43)-mediated intercellular communication has been implicated in tissue-adaptive and -maladaptive response to various chronic stresses. Here, we demonstrate that in hepatocytes, ERS results in increased Cx43 expression and cell-cell coupling. Co-culture of ER-stressed "donor" cells resulted in intercellular transmission of ERS and dysfunction to ERS-naive "recipient" cells ("bystander response"), which could be prevented by genetic or pharmacologic suppression of Cx43. Hepatocytes from obese mice were able to transmit ERS to hepatocytes from lean mice, and mice lacking liver Cx43 were protected from diet-induced ERS, insulin resistance, and hepatosteatosis. Taken together, our results indicate that in obesity, the increased Cx43-mediated cell-cell coupling allows intercellular propagation of ERS. This novel maladaptive response to over-nutrition exacerbates the tissue ERS burden, promoting hepatosteatosis and impairing whole-body glucose metabolism.

ObjectiveTo summarise the effects of herbal medications for the prevention of anxiety, depression, pain, and postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic, obstetrical/gynaecological or cardiovascular surgical procedures.MethodsSearches of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and LILACS up until January 2018 were performed to identify randomised controlled trials (RCTs). We included RCTs or quasi-RCTs evaluating any herbal medication among adults undergoing laparoscopic, obstetrical/gynaecological or cardiovascular surgeries. The primary outcomes were anxiety, depression, pain and PONV. We used the Grading of Recommendations Assessment, Development and Evaluation approach to rate overall certainty of the evidence for each outcome.ResultsEleven trials including 693 patients were eligible. Results from three RCTs suggested a statistically significant reduction in vomiting (relative risk/risk ratio (RR) 0.57; 95% CI 0.38 to 0.86) and nausea (RR 0.69; 95% CI 0.50 to 0.96) with the use ofZingiber officinale(ginger) compared with placebo in both laparoscopic and obstetrical/gynaecological surgeries. Results suggested a non-statistically significantly reduction in the need for rescue medication for pain (RR 0.52; 95% CI 0.13 to 2.13) withRosa damascena(damask rose) and ginger compared with placebo in laparoscopic and obstetrical/gynaecological surgery. None of the included studies reported on adverse events (AEs).ConclusionsThere is very low-certainty evidence regarding the efficacy of bothZingiber officinaleandRosa damascenain reducing vomiting (200 fewer cases per 1000; 288 fewer to 205 fewer), nausea (207 fewer cases per 1000; 333 fewer to 27 fewer) and the need for rescue medication for pain (666 fewer cases per 1000; 580 fewer to 752 more) in patients undergoing either laparoscopic or obstetrical/gynaecological surgeries. Among our eligible studies, there was no reported evidence on AEs.PROSPERO registration numberCRD42016042838

Summary: Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR) prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice. : Deterioration of metabolic health is a hallmark of aging and generally thought to be detrimental to longevity. Charles et al. utilize FABP-deficient mice as a model to demonstrate that the preservation of metabolic health in this model persists throughout life, even under metabolic stress, but does not increase longevity. Keywords: fatty acid binding protein, aging, calorie restriction, metabolic health, inflammation, metaflammation, diabetes, obesity, de novo lipogenesis

Introduction Postoperative nausea and vomiting (PONV) affect approximately 80% of surgical patients and is associated with increased length of hospital stay and systemic costs. Preoperative and postoperative pain, anxiety and depression are also commonly reported. Recent evidence regarding their safety and effectiveness has not been synthesised. The aim of this systematic review is to evaluate the efficacy and safety of herbal medications for the treatment and prevention of anxiety, depression, pain and PONV in patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgical procedures. Methods and analysis The following electronic databases will be searched up to 1 October 2016 without language or publication status restrictions: CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science and LILACS. Randomised clinical trials enrolling adult surgical patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgeries and managed with herbal medication versus a control group (placebo, no intervention or active control) prophylactically or therapeutically will be considered eligible. Outcomes of interest will include the following: anxiety, depression, pain, nausea and vomiting. A team of reviewers will complete title and abstract screening and full-text screening for identified hits independently and in duplicate. Data extraction, risk of bias assessments and evaluation of the overall quality of evidence for each relevant outcome reported will be conducted independently and in duplicate using the Grading of Recommendations Assessment Development and Evaluation classification system. Dichotomous data will be summarised as risk ratios; continuous data will be summarised as standard average differences with 95% CIs. Ethics and dissemination This is one of the first efforts to systematically summarise existing evidence evaluating the use of herbal medications in laparoscopic, obstetrical/gynaecological and cardiovascular surgical patients. The findings of this review will be disseminated through peer-reviewed publications and conference presentations. Systematic review registration PROSPERO CRD42016042838.

Proper function of the endoplasmic reticulum (ER) and mitochondria is crucial for cellular homeostasis, and dysfunction at either site has been linked to pathophysiological states, including metabolic diseases. Although the ER and mitochondria play distinct cellular roles, these organelles also form physical interactions with each other at sites defined as mitochondria-associated ER membranes (MAMs), which are essential for calcium, lipid and metabolite exchange. Here we show that in the liver, obesity leads to a marked reorganization of MAMs resulting in mitochondrial calcium overload, compromised mitochondrial oxidative capacity and augmented oxidative stress. Experimental induction of ER-mitochondria interactions results in oxidative stress and impaired metabolic homeostasis, whereas downregulation of PACS-2 or IP3R1, proteins important for ER-mitochondria tethering or calcium transport, respectively, improves mitochondrial oxidative capacity and glucose metabolism in obese animals. These findings establish excessive ER-mitochondrial coupling as an essential component of organelle dysfunction in obesity that may contribute to the development of metabolic pathologies such as insulin resistance and diabetes.

TNFalpha is an important mediator of catabolism in cachexia. Most of its effects have been characterized in peripheral tissues, such as skeletal muscle and fat. However, by acting directly in the hypothalamus, TNFalpha can activate thermogenesis and modulate food intake. Here we show that high concentration TNFalpha in the hypothalamus leads to increased O(2) consumption/CO(2) production, increased body temperature, and reduced caloric intake, resulting in loss of body mass. Most of the thermogenic response is produced by beta 3-adrenergic signaling to the brown adipose tissue (BAT), leading to increased BAT relative mass, reduction in BAT lipid quantity, and increased BAT mitochondria density. The expression of proteins involved in BAT thermogenesis, such as beta 3-adrenergic receptor, peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha, and uncoupling protein-1, are increased. In the hypothalamus, TNFalpha produces reductions in neuropeptide Y, agouti gene-related peptide, proopiomelanocortin, and melanin-concentrating hormone, and increases CRH and TRH. The activity of the AMP-activated protein kinase signaling pathway is also decreased in the hypothalamus of TNFalpha-treated rats. Upon intracerebroventricular infliximab treatment, tumor-bearing and septic rats present a significantly increased survival. In addition, the systemic inhibition of beta 3-adrenergic signaling results in a reduced body mass loss and increased survival in septic rats. These data suggest hypothalamic TNFalpha action to be important mediator of the wastage syndrome in cachexia.

Short-term response to cold promotes a small but significant rise in serum T3 in euthyroid rabbits, where the heart is an important target of T3 action. In this work, we measured changes in sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and phospholamban (PLB) in hearts of hypo- and hyperthyroid rabbits and compared them with modifications induced by short- and long-term cold exposure. Short-term cold exposure promotes a small increase in T3 and, similar to hyperthyroidism, induces an increase of heart SERCA2a expression. The total PLB content does not change in hyperthyroidism, but short-term cold exposure promotes a significant decrease in total PLB and an increase in the ratio between phosphorylated and total PLB. The temperature of a given tissue depends on the balance between the heat provided by blood circulation and the rate of heat production by the tissue. In an attempt to evaluate the heat contribution of cardiac tissue, we measured mitochondrial respiration in permeabilized cardiac muscle and heat produced by cardiac sarcoplasmic reticulum (SR) during Ca2+transport. We observed that there was an increase in oxygen consumption and heat production during Ca2+transport by cardiac SR in both hyperthyroidism and short-term cold exposure. In contrast, both the mitochondrial respiration rate and heat derived from Ca2+transport were decreased in hypothyroid rabbits. The heart changes in oxygen consumption, SERCA2a-PLB ratio, and Ca2+-ATPase activity detected during short-term cold exposure were abolished after cold adaptation. We hypothesize that the transient rise in serum T3 contributes to the short-term response to cold exposure.

Brown adipose tissue (BAT) is involved in rat and mice thermoregulation, and heat produced by BAT depends on the concerted action of thyroid hormones and catecholamines. Little is known about cold-induced thermogenesis in mammals that have little or no BAT, such as rabbits. In these animals, thermogenesis primarily occurs in skeletal muscle. In this work, we have studied the effect of cold acclimation (4 C for 10 d) in normal and hypothyroid rabbits. It is known that hypothyroid rats die after a few hours of cold exposure. We now show that, different from rats, hypothyroid rabbits sustain their body temperature and survive after 10 d cold exposure. When compared with rabbits kept at room temperature, the muscles of cold-exposed rabbits showed a dark red color characteristic of oxidative muscle fibers. According to this pattern, we observed that in both normal and hypothyroid rabbits, cold exposure promotes an increase in oxygen consumption by skeletal muscle mitochondria. Moreover, in red muscle, cold acclimation induces an increase in the expression and activity of sarcoplasmic reticulum Ca2+ ATPase isoform 1 (SERCA1), one of the muscle enzymes involved in heat production. We conclude that rabbit cold tolerance is probably related to increased muscle oxidative metabolism and heat production by SERCA1 and that these changes are not completely dependent on normal thyroid function.

The sarcoplasmic reticulum Ca(2+) ATPase 1 (SERCA 1) is able to handle the energy derived from ATP hydrolysis in such a way as to determine the parcel of energy that is used for Ca(2+) transport and the fraction that is converted into heat. In this work we measured the heat production by SERCA 1 in the two sarcoplasmic reticulum (SR) fractions: the light fraction (LSR), which is enriched in SERCA and the heavy fraction (HSR), which contains both the SERCA and the ryanodine Ca(2+) channel. We verified that although HSR cleaved ATP at faster rate than LSR, the amount of heat released during ATP hydrolysis by HSR was smaller than that measured by LSR. Consequently, the amount of heat released per mol of ATP cleaved (DeltaH(cal)) by HSR was lower compared to LSR. In HSR, the addition of 5 mM Mg(2+) or ruthenium red, conditions that close the ryanodine Ca(2+) channel, promoted a decrease in the ATPase activity, but the amount of heat released during ATP hydrolysis remained practically the same. In this condition, the DeltaH(cal) values of ATP hydrolysis increased significantly. Neither Mg(2+) nor ruthenium red had effect on LSR. Thus, we conclude that heat production by SERCA 1 depends on the region of SR in which the enzyme is inserted and that in HSR, the DeltaH(cal) of ATP hydrolysis by SERCA 1 depends on whether the ryanodine Ca(2+) channel is opened or closed.

A number of chronic metabolic pathologies, including obesity, diabetes, cardiovascular disease, asthma, and cancer cluster together to present the greatest threat to human health. As research in this field has advanced, it has become clear that unresolved metabolic inflammation, organelle dysfunction, and other cellular and metabolic stresses underlie the development of these chronic metabolic diseases. However, the relationship between these systems and pathological mechanisms is poorly understood. Here, we will discuss the role of cellular Ca2+ homeostasis as a critical mechanism integrating the myriad of cellular and subcellular dysfunctional networks found in metabolic tissues such as liver and adipose tissue in the context of metabolic disease particularly in obesity and diabetes.