A patogênese da Cardiomiopatia Chagásica Crônica (CCC) ainda é assunto de intenso debate. A CCC apresenta intenso infiltrado inflamatório no tecido cardíaco, onde os linfócitos T infiltrantes produzem citocinas inflamatórias, como IFN-gama e TNF-alfa. Adicionalmente, pacientes com CCC apresentam um pior prognóstico quando comparados aos portadores de outras cardiomiopatias de etiologia não inflamatória, como a cardiomiopatia dilatada idiopática (CDI) e a cardiomiopatia isquêmica (CI), sugerindo que mecanismos inflamatórios participam da patogênese e evolução da doença. Além disso, evidências anteriores de nosso grupo indicaram alterações do metabolismo energético na CCC. Neste trabalho, comparamos a expressão protéicado miocárdio de pacientes com CCC, CDI e CI e indivíduos sem cardiomiopatias, com foco em proteínas relacionadas ao metabolismo energético celular. Para a identificação do perfil de expressão protéica no miocárdio de pacientes com CCC, utilizamos a técnica de separação por eletroforese bidimensional, e a identificação das proteínas foi feita por espectrometria de massa. A maioria dos spots identificados corresponde a proteínas estruturais ou proteínas do metabolismo, principalmente do metabolismo energético. Foram identificadas também proteínas envolvidas na apoptose...

Objetivo. O objetivo do estudo foi analisar a influência da ingestão alimentar de proteína da soja enriquecida com isoflavona e dos exercícios com pesos sobre o metabolismo energético de mulheres na pós-menopausa. Casuística e métodos. Ensaio clínico, 16 semanas, envolvendo 60 mulheres, 59 (7) anos, distribuídas em 4 grupos: G1 (proteína da soja e exercício), G2 (placebo e exercício), G3 (proteína da soja e sem exercício) e G4 (placebo e sem exercício). A proteína da soja e o placebo (maltodextrina) foram distribuídos, aleatoriamente, sob a forma de pó, na porção de 25 gramas/dia, enriquecida com 50 mg de isoflavona. Foram 10 exercícios com pesos, realizados em 3 sessões semanais, com 3 séries de 8-12 repetições cada, carga de 60-80% de 1 repetição máxima (RM). O metabolismo energético foi analisado a partir do gasto energético de repouso (GER) e do quociente respiratório (QR). O GER foi calculado utilizando o O2 e o CO2, obtidos por calorimetria indireta (Quinton-QMC®), durante 30 minutos, sob temperatura e umidade controladas, e o QR pela relação CO2/O2. Foram utilizadas variáveis de controle: idade, hormônio folículo estimulantes (FSH), proteína e valor calórico total da alimentação (VCT)...

O meio ambiente urbano vem sofrendo drásticas transformações ao longo destas últimas décadas. E um dos principais problemas é o aumento significativo da poluição atmosférica devido ao metabolismo realizado pela frota de veículos motorizados e indústrias instaladas nos centros urbanos. Neste trabalho, a cidade é compreendida como um sistema aberto e vista como um organismo vivo, que se alimenta de recursos naturais, realiza seu próprio metabolismo, produz resíduos, como subprodutos resultantes deste metabolismo, sob a forma de emissão gasosa, liquida e sólida que agridem e desequilibram o meio biogeofísico e afetam a comunidade al residente, bem como de regiões circunvizinhas e até bem distantes. Uma cidade ou um de seus sistemas podem ser considerados como possuidor de um metabolismo eficiente, quando consomem menos energia ou recurso natural para realizar as mesmas funções de manutenção, de geração de serviços, de crescimento urbano e de desenvolvimento sócio-econômico, produzindo menores quantidades de emissões, diminuindo os impactos negativos sobre o meio biogeofísico. Por meio de uma abordagem sistêmica e multidisciplinar, utilizado o modelo do metabolismo de uma cidade, focaliza-se no metabolismo energético do sistema de transportes. Como estudo de caso a cidade de Curitiba...

Obesity is rampant in modern society and growth hormone (GH) could be useful as adjunct therapy to reduce the obesity-induced cardiovascular damage. To investigate GH effects on obesity, initially 32 male Wistar rats were divided into two groups (n = 16): control (C) was fed standard-chow and water and hyper-caloric (H) was fed hypercaloric chow and 30% sucrose in its drinking water. After 45 days, both C and H groups were divided into two subgroups (n = 8): C + PL was fed standard-chow, water and received saline subcutaneously; C + GH was fed standard-chow, water, and received 2 mg/kg/day GH subcutaneously; H + PL was fed hypercaloric diet, 30% sucrose in its drinking water, and received saline subcutaneously; and H + GH was fed hypercaloric diet, 30% sucrose in its drinking water, and received GH subcutaneously. After 75 days of total experimental period, H + PL rats were considered obese, having higher body weight, body mass index, Lee-index, and atherogenic index (AI) compared to C + PL. Obesity was accompanied by enhanced myocardial lipid hydroperoxide (LH) and lactate dehydrogenase (LDH), as well of depressed energy expenditure (RMR) and oxygen consumption(VO(2))/body weight. H + GH rats had higher fasting RMR, as well as lower AI and myocardial LH than H + PL. Comparing C + GH with C + PL...

Several evidences point for beneficial effects of growth hormone (GH) in heart failure (HF). Taking into account that HF is related with changes in myocardial oxidative stress and in energy generation from metabolic pathways, it is important to clarify whether GH increase or decrease myocardial oxidative stress and what is its effect on energetic metabolism in HF condition. Thus, this study investigated the effects of two different doses of GH on energetic metabolism and oxidative stress in myocardium of rats with HF. Male Wistar rats (n = 25) were submitted to aortic stenosis (AS). The HF was evidenced by tachypnea and echocardiographic criteria around 28 weeks of AS. The rats were then randomly divided into three groups: (HF) with HF, treated with saline (0.9% NaCl); (HF-GHI), treated with 1 mk/kg/day recombinant human growth hormone (rhGH), and (HF-GH2) treated with 2 mg/kg/day rhGH. GH was injected, subcutaneously, daily for 2 weeks. A control group (sham; n = 12), with the same age of the others rats was evaluated to confirm data for AS. HF had lower IGF-I (insulin-like growth factor-I) than sham-operated rats, and both GH treatments normalized IGF-I level. HF-GH1 animals had lower lipid hydroperoxide (LH), LH/total antioxidant substances (TAS) and glutathione-reductase than HF. Glutathione peroxidase (GSH-Px)...

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Alcoholism has been associated with a wide range of pathologic conditions, including alcoholic heart disease (AHD). Because AHD may be associated with oxidative stress, antioxidant compounds, such as N-acetylcysteine (NAC) could be useful to control the damage done by alcohol (ethanol) consumption. To investigate the NAC effects on alcoholism and alcohol abstinence, initially, 30 male Wistar rats were divided into two groups: (C, N = 6) given standard chow and water; (E, N = 24) receiving standard chow and aqueous ethanol solution in semi-voluntary research. After 30 days of ethanol-exposure, (E) group was divided into four subgroups (N = 6/group):(E-E) continued drinking 30% ethanol-solution; (E-NAC) drinking ethanol-solution containing 2 g/L NAC; (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution of 2 g/L NAC. After 15 days of the E-group division, E-E rats had lower body weight and feed efficiency, as well as higher energy-expenditure resting metabolic rate (RMR)/body weight and VO(2) consumption/surface area. These calorimetric changes were reflected on the cardiac tissue. E-E rats had higher heart weight/body weight ratio and myocardial lipid hydroperoxide (LH)...

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); To study the effects of N-acetylcysteine (NAC, C(5)H(9)-NO(3)S) on high-sucrose diet-induced obesity and its effects on energy metabolism and cardiac oxidative stress, male Wistar 24 rats were divided into four groups (n = 6): (C) given standard chow and water; (N) receiving standard chow and 2 g/l N-acetylcysteine in its drinking water; (HS) given standard chow and 30% sucrose in its drinking water, and (HS-N) receiving standard chow, 30% sucrose and N-acetylcysteine in its drinking water.After 30 days of the treatment, obesity was evidenced in HS rats from enhanced body weight, respiratory quotient, hypertriglyceridemia. As well depressed resting metabolic rate, and oxygen consumption per surface area. HS rats had triacylglycerol accumulation, oxidative stress and metabolic shifting in cardiac tissue. NAC enhanced fat oxidation and energy expenditure, normalizing these adverse effects, comparing HS-N and HS rats. The beta-hydroxyacyl coenzymne-A dehydrogenase activity was higher in HS-N animals, indicating higher heart fatty acid degradation than in HS. NAC normalized myocardial glycogen and lactate dehydrogenase activity...

The objective of the present study was to investigate the effects of dietary macronutrient ratio on energy metabolism and on skeletal muscle mRNA expression of avian uncoupling protein (UCP), thought to be implicated in thermogenesis in birds. Broiler chickens from 2 to 6 weeks of age received one of three isoenergetic diets containing different macronutrient ratios (low-lipid (LL) 30 v. 77 g lipid/kg-, low-protein (LP) 125 v. 197 g crude protein (N X 6.25)/kg; low-carbohydrate (LC) 440 v. 520 g carbohydrate/kg). LP chickens were characterised by significantly lower body weights and food intakes compared with LL and LC chickens (-47 and -38% respectively) but similar heat production/kg metabolic body weight, as measured by indirect calorimetry, in the three groups. However, heat production/g food ingested was higher in animals receiving the LP diet (+41%, P<0.05). These chickens also deposited 57% less energy as protein (P<0.05) and 33% more as fat. No significant differences in energy and N balances were detected between LL and LC chickens. The diets with the higher fat contents (i.e. The LP and LC diets) induced slightly but significantly higher relative expressions of avian UCP mRNA in gastrocnemius muscle, measured by reverse transcription-polymerase chain reaction...

Recent lines of evidence suggest that the beneficial effects of olive oil are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. The aim of this work was determine the effects of olive oil and its components, oleic acid and the polyphenol dihydroxyphenylethanol (DPE), on serum lipids, oxidative stress, and energy metabolism on cardiac tissue. Twenty four male Wistar rats, 200 g, were divided into the following 4 groups (n = 6): control (C), OO group that received extra-virgin olive oil (7.5 mL/kg), OA group was treated with oleic acid (3.45 mL/kg), and the DPE group that received the polyphenol DPE (7.5 mg/kg). These components were administered by gavage over 30 days, twice a week. All animals were provided with food and water ad libitum The results show that olive oil was more effective than its isolated components in improving lipid profile, elevating high-density lipoprotein, and diminishing low-density lipoprotein cholesterol concentrations. Olive oil induced decreased antioxidant Mn-superoxide dismutase activity and diminished protein carbonyl concentration, indicating that olive oil may exert direct antioxidant effect on myocardium. DPE, considered as potential antioxidant...

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Obesity is often associated with decreased fat oxidation and aging is a well-recognized risk factor for cardiovascular disease. This study investigated calorimetric and morphometric parameters, as well as the glucose levels, lipid profile and cardiac energy metabolism in young and old, controls and obese rats. The animals were divided into four groups: Group I (GI): young rats fed normal diet for 75 days; Group II (GII): young rats fed hypercaloric diet (HD) for 75 days; Group III (GIII): old rats fed normal diet for 510 days; and Group IV (G IV): old rats fed HD for 510 days. The following analyses were performed: calorimetric, glucose and lipid concentrations, atherogenic index (AI), total antioxidant substances (TAS), fat depots, cardiac lipid hydroperoxide (LH) and cardiac lactate dehydrogenase (LDH), citrate synthase (CS), phosphofructokinase (PFK) and pyruvate dehydrogenase (PDH) activities. Older animals were heavier than young and the hypercaloric animals were heavier than controls. Animals from GIV had lower fat oxidation than GIII, which in turn, had higher fat oxidation than GI. Total cholesterol...

Fatty acids are the main substrates used by mitochondria to provide myocardial energy under normal conditions. During heart remodeling, however, the fuel preference switches to glucose. In the earlier stages of cardiac remodeling, changes in energy metabolism are considered crucial to protect the heart from irreversible damage. Furthermore, low fatty acid oxidation and the stimulus for glycolytic pathway lead to lipotoxicity, acidosis, and low adenosine triphosphate production. While myocardial function is directly associated with energy metabolism, the metabolic pathways could be potential targets for therapy in heart failure. © 2013 by Lippincott Williams & Wilkins.

A melatonina (MLT) é um neurohormônio presente em humanos e outros vertebrados, sendo a glândula pineal principal fonte produtora. Além de sua conhecida ação cronobiológica, a MLT tem papel regulador sobre o metabolismo energético e sobre a massa corporal de mamíferos. A presença de receptores para MLT nos núcleos hipotalâmicos dorso-medial, supraquiasmático, paraventricular do hipotálamo desde a fase embrionária, corrobora a mediação da MLT no controle neural do metabolismo. Dentro deste contexto o presente trabalho avaliou os efeitos da administração de MLT sobre a evolução ponderal e os níveis plasmáticos de glicose, triglicérides, colesterol, ácido graxo livre e insulina. Também foram investigados os efeitos da MLT sobre a fosforilação da AKT e ERK1/2 no hipotálamo de ratos neonatos. Neste estudo foram utilizados ratos neonatos com dois dias de vida (P2) que receberam doses diárias de MLT (1, 10, 50 e 100 mg/kg, s.c.; n=10) e/ou luzindole, antagonista não seletivo da MLT (1 mg/kg, s.c.; n=10). Os animais foram tratados por seis dias e sacrificados 24 horas após a última dose (P8). Três grupos adicionais foram utilizados, dois deles receberam apenas os veículos de diluição da melatonia (n=10) ou luzindole (n=10). O terceiro foi formado por animais não tratados (n=10). Imediatamente após o sacrifício foi coletado sangue para as dosagens plasmáticas...

The metabolic profiles of selected tissues were analyzed in hatchlings of the Amazonian freshwater turtles Podocnemis expansa, P. unifilis and P. sextuberculata. Metabolic design in these species was judged based on the key enzymes of energy metabolism, with special emphasis on carbohydrate, lipid, amino acid and ketone body metabolism. All species showed a high glycolytic potential in all sampled tissues. Based on low levels of hexokinase, glycogen may be an important fuel for these species. The high lactate dehydrogenase activity in the liver may play a significant role in carbohydrate catabolism, possibly during diving. Oxidative metabolism in P. sextuberculata appears to be designed for the use of lipids, amino acids and ketone bodies. The maximal activities of 3-hydroxyacyl-CoA dehydrogenase, malate dehydrogenase, glutamine dehydrogenase, alanine aminotransferase and succinyl-CoA keto transferase display high aerobic potential, especially in muscle and liver tissues of this species. Although amino acids and ketone bodies may be important fuels for oxidative metabolism, carbohydrates and lipids are the major fuels used by P. expansa and P. unifilis. Our results are consistent with the food habits and lifestyle of Amazonian freshwater turtles. The metabolic design...

Inorganic polyphosphate (poly P) is a polymer made from as few as 10 to several hundred phosphate molecules linked by phosphoanhydride bonds similar to ATP. Poly P is ubiquitous in all mammalian organisms, where it plays multiple physiological roles. The metabolism of poly P in mammalian organisms is not well understood. We have examined the mechanism of poly P production and the role of this polymer in cell energy metabolism. Poly P levels in mitochondria and intact cells were estimated using a fluorescent molecular probe, 4′,6-diamidino-2-phenylindole. Poly P levels were dependent on the metabolic state of the mitochondria. Poly P levels were increased by substrates of respiration and in turn reduced by mitochondrial inhibitor (rotenone) or an uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone). Oligomycin, an inhibitor of mitochondrial ATP-synthase, blocked the production of poly P. Enzymatic depletion of poly P from cells significantly altered the rate of ATP metabolism. We propose the existence of a feedback mechanism where poly P production and cell energy metabolism regulate each other.

The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation...

Objective: To investigate the impact of whole body C5a receptor (C5aR) deficiency on energy metabolism and fat storage. Design: Male wildtype (WT) and C5aR knockout (C5aRKO) mice were fed a low fat (CHOW) or a high fat high sucrose diet-induced obesity (DIO) diet for 14 weeks. Body weight and food intake were measured weekly. Indirect calorimetry, dietary fatload clearance, insulin and glucose tolerance tests were also evaluated. Liver, muscle and adipose tissue mRNA gene expression were measured by RT-PCR. Results: At week one and 12, C5aRKO mice on DIO had increased oxygen consumption. After 12 weeks, although food intake was comparable, C5aRKO mice had lower body weight (−7% CHOW, −12% DIO) as well as smaller gonadal (−38% CHOW, −36% DIO) and inguinal (−29% CHOW, −30% DIO) fat pads than their WT counterparts. Conversely, in WT mice, C5aR was upregulated in DIO vs CHOW diets in gonadal adipose tissue, muscle and liver, while C5L2 mRNA expression was lower in C5aRKO on both diet. Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload. Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets...

Leishmaniasis is a neglected tropical disease responsible for physical, economic and social damages. Even though malaria is not classified as a neglected tropical disease, is responsible for high morbidity and mortality, especially in African countries. Current treatments for both diseases face several drawbacks, including the evolution of drugresistant parasites, the high cost of major drugs and the high toxicity of others. For these reasons, there is an urgent need to develop new drugs that minimize these downsides and, consequently, help eradicate these diseases. To overcome these difficulties, both academics and pharmaceutical companies are increasingly employing the so-called “drug repositioning strategy”. Drug repositioning aims to find new applications for drugs approved for other indications, and has proven valuable for decreasing research costs as well as to decrease the time required to market the "new" drug. In the present study, we used bioinformatics to identify and analyze molecular targets of the energy metabolism of Leishmania spp and of the P. falciparum apicoplast. The energy metabolism of Leishmania and the apicoplast metabolism have various enzymes that can be targeted by specific drugs, leading to lower toxicity and more promising therapies for humans. Using the TDR Targets database...

Energy failure is a possible pathogenic component of a number of common blinding disorders, including vascular retinopathies, glaucoma, and age-related macular degeneration. An overarching premise of the bioenergetics-based research from the research group in which I conducted my studies is that if energy failure constitutes a pathogenic component in ocular disease, then provision of energy or the means of the diseased tissue to create its own additional energy may well presented a valid and viable therapeutic solution. One such approach has been to provide an additional supply of glucose to a tissue since this monosaccharide is used by the majority of cells as the primary fuel source for the generation of cellular energy in the form of adenosine triphosphate (ATP). Previous in vivo research from the group has demonstrated that elevated vitreal glucose levels afforded robust neuroprotection to the retina and optic nerve in experimental model of acute and subacute ischaemic retinal injury, and in a rat model of laser-induced glaucoma. The current research focussed on aspects of retinal energy metabolism, and in particular, the mechanisms by which glucose can act as a neuroprotectant under conditions of compromised energy production in the retina. Another aim was to translate this research to the clinic and assess the effect of elevated vitreal glucose levels on visual function in glaucoma patients. The current thesis comprises four original papers and one perspectives paper. The first paper characterised an in vitro model of metabolic impairment to rat retinal cultures...

FUNDAMENTO: Anormalidades do metabolismo miocárdico têm sido observadas em pacientes com insuficiência cardíaca de diferentes etiologias. A espectroscopia por ressonância magnética (ERM) com fósforo 31 é uma técnica não invasiva que permite a detecção de alterações metabólicas miocárdicas. OBJETIVO: Determinar o metabolismo de repouso dos fosfatos de alta energia em pacientes portadores de doença de Chagas (DC) pela ERM com fósforo 31. MÉTODOS: Foram estudados 39 pacientes com DC, sendo 23 com função ventricular preservada (Grupo FP) e 16 com disfunção ventricular (Grupo DV), avaliados pela ecodopplercardiografia. A ERM da região anterosseptal foi realizada nos 39 pacientes e em 8 indivíduos normais (Grupo C), por meio de um aparelho Phillips de 1,5 Tesla, obtendo-se a relação fosfocreatina/trifosfato de adenosina beta (PCr/β-ATP) miocárdicos. RESULTADOS: Os níveis cardíacos de PCr/β-ATP estavam reduzidos no Grupo DV em relação ao Grupo FP, e estes apresentaram níveis reduzidos em relação ao Grupo C (Grupo DV: 0,89 ± 0,31 vs Grupo FP: 1,47 ± 0,34 vs Grupo C: 1,88 ± 0,08, p < 0,001). Houve correlação entre a fração de ejeção do ventrículo esquerdo e a PCr/β-ATP nos 39 pacientes estudados (r = 0...

Contributed to: Joint Meeting of the American Society of Animal Science (ASAS), the American Dairy Science Association (ADSA) & the Poultry Science Association (PSA), St. Louis, Missouri, USA, Jul 25-29, 2004.; Trans-10, cis-12 conjugated linoleic acid (CLA) inhibits milk fat synthesis and reduces milk energy content. Controlled decreases in milk energy secretion could be used to improve energy balance of the dairy cow during early lactation. Twelve multi-parous Holstein-British Friesian cows were used in a randomized block study to evaluate the effects of rumen protected CLA (RCLA) on energy metabolism in early lactation. Supplements were prepared by casein-formaldehyde treatment of CLA methyl esters containing equal amounts of cis-9, trans-11 and trans-10, cis-12. At calving, cows were paired and allocated at random to a control diet (C) or the same diet supplemented with 110 g of RCLA that supplied 14.3 g trans-10, cis-12 CLA/d. Energy balance (MJ/d) was estimated during weeks 3, 7, 11 and 15 of lactation using 6d excreta collection and respiration calorimetry. On average, RCLA reduced milk fat content (34.9 vs. 19.2 g/kg; P<0.001) and milk fat yield (1395 vs. 901 g/d; P<0.001), increased (P<0.05) milk yield (40.3 vs. 47.4 kg/d) and milk protein output (1.25 vs. 1.42 kg/d) and tended to increase DMI (22.2 vs. 24.6 kg/d; P=0.06) and BW (614 vs. 661 kg; P=0.11). The effects on DMI and production occurred within one week of lactation. RCLA increased (P=0.08) energy intake (389 vs. 434...