Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.556
Filtrar
1.
Eur J Endocrinol ; 185(4): 553-563, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34342595

RESUMO

Objective: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. Design: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. Results: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). Conclusion: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.


Assuntos
Tecido Adiposo Marrom/metabolismo , Hipertireoidismo/metabolismo , Hipertireoidismo/reabilitação , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/efeitos dos fármacos , Adulto , Idoso , Antitireóideos/farmacologia , Antitireóideos/uso terapêutico , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Carbimazol/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Fluordesoxiglucose F18 , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Doença de Graves/reabilitação , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Indução de Remissão , Singapura , Termogênese/efeitos dos fármacos , Termogênese/fisiologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologia , Adulto Jovem
2.
J Laryngol Otol ; 135(9): 779-784, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34448687

RESUMO

OBJECTIVE: Cells in the vocal fold of maculae flavae are likely to be tissue stem cells. Energy metabolism of the cells in newborn maculae flavae was investigated from the aspect of mitochondrial microstructure. METHOD: Five normal newborn vocal folds were investigated under transmission electron microscopy. RESULTS: Mitochondria consisted of a double membrane bounded body containing matrices and a system of cristae. However, these membranes were ambiguous. In each mitochondrion, the lamellar cristae were sparse. Intercristal space was occupied by a mitochondrial matrix. Some mitochondria had fused to lipid droplets and rough endoplasmic reticulum, and both the mitochondrial outer and inner membranes had incarcerated and disappeared. CONCLUSION: The features of the mitochondria of the cells in the newborn maculae flavae showed that their metabolic activity and oxidative phosphorylation were low. The metabolism of the cells in the newborn maculae flavae seems to be favourable to maintain the stemness and undifferentiation of the cells.


Assuntos
Metabolismo Energético/fisiologia , Mucosa Laríngea/metabolismo , Mitocôndrias/ultraestrutura , Prega Vocal/citologia , Humanos , Recém-Nascido
3.
Nat Commun ; 12(1): 4773, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362885

RESUMO

The relationship between the age-associated decline in mitochondrial function and its effect on skeletal muscle physiology and function remain unclear. In the current study, we examined to what extent physical activity contributes to the decline in mitochondrial function and muscle health during aging and compared mitochondrial function in young and older adults, with similar habitual physical activity levels. We also studied exercise-trained older adults and physically impaired older adults. Aging was associated with a decline in mitochondrial capacity, exercise capacity and efficiency, gait stability, muscle function, and insulin sensitivity, even when maintaining an adequate daily physical activity level. Our data also suggest that a further increase in physical activity level, achieved through regular exercise training, can largely negate the effects of aging. Finally, mitochondrial capacity correlated with exercise efficiency and insulin sensitivity. Together, our data support a link between mitochondrial function and age-associated deterioration of skeletal muscle.


Assuntos
Envelhecimento/fisiologia , Metabolismo Energético/fisiologia , Exercício Físico/psicologia , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Am J Health Behav ; 45(4): 756-770, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34340742

RESUMO

Objectives: Cross-sectional reports on weight gain during the COVID-19 shelter-at-home have raised concerns for weight increases as the pandemic continues. We examined behaviors that impact energy intake and/or energy expenditure among adults in the United States during shelter-at-home. Methods: Cross-sectional data (N=1779; April 24 - May4, 2020) were collected on demographics, diet, physical activity, sleep, and food purchasing behaviors. Percent of participants reporting increase/ decrease/no change in these behaviors during the COVID-19 shelter-at-home were assessed. Each analysis was followed by comparing whether increases or decreases were more likely for each health behavior, in all participants and across sex (43.38% males). Results: Increased consumption of healthy foods, energy-dense unhealthy foods, and snacks, and increased sedentary activities (p < .001) was reported. Physical activity and alcohol intake declined (p < .001). Females were more likely than males (p < .001) to report ultra-processed foods/high-calorie snack intake, fruit/vegetable intake (p < .001) and increase (p < .01) sleep and sedentary behavior. Conclusion: Acute behavioral changes supporting greater energy intake and less energy expenditure, especially in females, underscore the significance of COVID-19-related increase in unstructured time. Longitudinal assessment of body weight and health behaviors is warranted to understand the impact of pandemic.


Assuntos
COVID-19/prevenção & controle , Ingestão de Energia , Metabolismo Energético , Comportamento Alimentar , Comportamentos Relacionados com a Saúde , Distanciamento Físico , Comportamento Sedentário , Adulto , Estudos Transversais , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Comportamento Alimentar/fisiologia , Feminino , Comportamentos Relacionados com a Saúde/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Estados Unidos
5.
Clin Nutr ESPEN ; 44: 211-217, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34330468

RESUMO

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can rapidly progress into acute respiratory distress syndrome accompanied by multi-organ failure requiring invasive mechanical ventilation and critical care treatment. Nutritional therapy is a fundamental pillar in the management of hospitalized patients. It is broadly acknowledged that overfeeding and underfeeding of intensive care unit (ICU) patients are associated with increased morbidity and mortality. This study aimed to assess the energy demands of long-term ventilated COVID-19 patients using indirect calorimetry and to evaluate the applicability of established predictive equations to estimate their energy expenditure. METHODS: We performed a retrospective, single-center study in 26 mechanically ventilated COVID-19 patients with resolved SARS-CoV-2 infection in three independent intensive care units. Resting energy expenditure (REE) was evaluated by repetitive indirect calorimetry (IC) measurements. Simultaneously the performance of 12 predictive equations was examined. Patient's clinical data were retrieved from electronic medical charts. Bland-Altman plots were used to assess agreement between measured and calculated REE. RESULTS: Mean mREE was 1687 kcal/day and 20.0 kcal relative to actual body weight (ABW) per day (kcal/kg/day). Longitudinal mean mREE did not change significantly over time, although mREE values had a high dispersion (SD of mREE ±487). Obese individuals were found to have significantly increased mREE, but lower energy expenditure relative to their body mass. Calculated REE showed poor agreement with mREE ranging from 33 to 54%. CONCLUSION: Resolution of SARS-CoV-2 infection confirmed by negative PCR leads to stabilization of energy demands at an average 20 kcal/kg in ventilated critically ill patients. Due to high variations in mREE and low agreement with calculated energy expenditure IC remains the gold standard for the guidance of nutritional therapy.


Assuntos
COVID-19/fisiopatologia , Cuidados Críticos/métodos , Metabolismo Energético/fisiologia , Necessidades Nutricionais/fisiologia , Respiração Artificial/métodos , Calorimetria Indireta , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Tempo
6.
Nat Commun ; 12(1): 4312, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257310

RESUMO

Physical inactivity is the fourth leading cause of global mortality. Health organizations have requested a tool to objectively measure physical activity. Respirometry and doubly labeled water accurately estimate energy expenditure, but are infeasible for everyday use. Smartwatches are portable, but have significant errors. Existing wearable methods poorly estimate time-varying activity, which comprises 40% of daily steps. Here, we present a Wearable System that estimates metabolic energy expenditure in real-time during common steady-state and time-varying activities with substantially lower error than state-of-the-art methods. We perform experiments to select sensors, collect training data, and validate the Wearable System with new subjects and new conditions for walking, running, stair climbing, and biking. The Wearable System uses inertial measurement units worn on the shank and thigh as they distinguish lower-limb activity better than wrist or trunk kinematics and converge more quickly than physiological signals. When evaluated with a diverse group of new subjects, the Wearable System has a cumulative error of 13% across common activities, significantly less than 42% for a smartwatch and 44% for an activity-specific smartwatch. This approach enables accurate physical activity monitoring which could enable new energy balance systems for weight management or large-scale activity monitoring.


Assuntos
Metabolismo Energético/fisiologia , Perna (Membro)/fisiologia , Caminhada/fisiologia , Dispositivos Eletrônicos Vestíveis , Exercício Físico/fisiologia , Humanos
7.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203322

RESUMO

BACKGROUND: In space, the reduction or loss of the gravity vector greatly affects the interaction between cells. Since the beginning of the space age, microgravity has been identified as an informative tool in biomedicine, including cancer research. The A549 cell line is a hypotriploid human alveolar basal epithelial cell line widely used as a model for lung adenocarcinoma. Microgravity has been reported to interfere with mitochondrial activity, energy metabolism, cell vitality and proliferation, chemosensitivity, invasion and morphology of cells and organelles in various biological systems. Concerning lung cancer, several studies have reported the ability of microgravity to modulate the carcinogenic and metastatic process. To investigate these processes, A549 cells were exposed to simulated microgravity (µG) for different time points. METHODS: We performed cell cycle and proliferation assays, ultrastructural analysis of mitochondria architecture, as well as a global analysis of miRNA modulated under µG conditions. RESULTS: The exposure of A549 cells to microgravity is accompanied by the generation of polynucleated cells, cell cycle imbalance, growth inhibition, and gross morphological abnormalities, the most evident are highly damaged mitochondria. Global miRNA analysis defined a pool of miRNAs associated with µG solicitation mainly involved in cell cycle regulation, apoptosis, and stress response. To our knowledge, this is the first global miRNA analysis of A549 exposed to microgravity reported. Despite these results, it is not possible to draw any conclusion concerning the ability of µG to interfere with the cancerogenic or the metastatic processes in A549 cells. CONCLUSIONS: Our results provide evidence that mitochondria are strongly sensitive to µG. We suggest that mitochondria damage might in turn trigger miRNA modulation related to cell cycle imbalance.


Assuntos
MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Células A549 , Células Epiteliais Alveolares/citologia , Células Epiteliais Alveolares/metabolismo , Ciclo Celular/genética , Ciclo Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Metabolismo Energético/fisiologia , Humanos
8.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299261

RESUMO

Many approaches have been used in the effective management of type 2 diabetes mellitus. A recent paradigm shift has focused on the role of adipose tissues in the development and treatment of the disease. Brown adipose tissues (BAT) and white adipose tissues (WAT) are the two main types of adipose tissues with beige subsets more recently identified. They play key roles in communication and insulin sensitivity. However, WAT has been shown to contribute significantly to endocrine function. WAT produces hormones and cytokines, collectively called adipocytokines, such as leptin and adiponectin. These adipocytokines have been proven to vary in conditions, such as metabolic dysfunction, type 2 diabetes, or inflammation. The regulation of fat storage, energy metabolism, satiety, and insulin release are all features of adipose tissues. As such, they are indicators that may provide insights on the development of metabolic dysfunction or type 2 diabetes and can be considered routes for therapeutic considerations. The essential roles of adipocytokines vis-a-vis satiety, appetite, regulation of fat storage and energy, glucose tolerance, and insulin release, solidifies adipose tissue role in the development and pathogenesis of diabetes mellitus and the complications associated with the disease.


Assuntos
Tecido Adiposo/metabolismo , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Adipocinas/metabolismo , Adiponectina/metabolismo , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Metabolismo Energético/fisiologia , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Leptina/metabolismo , Obesidade/metabolismo
9.
Int J Mol Sci ; 22(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34299350

RESUMO

Leptin is a cytokine that regulates appetite and energy expenditure, where in fishes it is primarily produced in the liver and acts to mobilize carbohydrates. Most fishes have only one leptin receptor (LepR/LepRA1), however, paralogs have recently been documented in a few species. Here we reveal a second leptin receptor (LepRA2) in rainbow trout that is 77% similar to trout LepRA1. Phylogenetic analyses show a salmonid specific genome duplication event as the probable origin of the second LepR in trout. Tissues distributions showed tissue specific expression of these receptors, with lepra1 highest in the ovaries, nearly 50-fold higher than lepra2. Interestingly, lepra2 was most highly expressed in the liver while hepatic lepra1 levels were low. Feed deprivation elicited a decline in plasma leptin, an increase in hepatic lepra2 by one week and remained elevated at two weeks, while liver expression of lepra1 remained low. By contrast, muscle lepra1 mRNA increased at one and two weeks of fasting, while adipose lepra1 was concordantly lower in fasted fish. lepra2 transcript levels were not affected in muscle and fat. These data show lepra1 and lepra2 are differentially expressed across tissues and during feed deprivation, suggesting paralog- and tissue-specific functions for these leptin receptors.


Assuntos
Oncorhynchus mykiss/metabolismo , Receptores para Leptina/metabolismo , Tecido Adiposo/metabolismo , Sequência de Aminoácidos , Animais , Apetite/fisiologia , Metabolismo Energético/fisiologia , Jejum/metabolismo , Proteínas de Peixes/metabolismo , Leptina/metabolismo , Fígado/metabolismo , Músculos/metabolismo , Filogenia , RNA Mensageiro/metabolismo , Alinhamento de Sequência
10.
Theranostics ; 11(14): 6682-6702, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093847

RESUMO

Cancers in animals present a large, underutilized reservoir of biomedical information with critical implication for human oncology and medicine in general. Discussing two distinct areas of tumour biology in non-human hosts, we highlight the importance of these findings for our current understanding of cancer, before proposing a coordinated strategy to harvest biomedical information from non-human resources and translate it into a clinical setting. First, infectious cancers that can be transmitted as allografts between individual hosts, have been identified in four distinct, unrelated groups, dogs, Tasmanian devils, Syrian hamsters and, surprisingly, marine bivalves. These malignancies might hold the key to improving our understanding of the interaction between tumour cell and immune system and, thus, allow us to devise novel treatment strategies that enhance anti-cancer immunosurveillance, as well as suggesting more effective organ and stem cell transplantation strategies. The existence of these malignancies also highlights the need for increased scrutiny when considering the existence of infectious cancers in humans. Second, it has long been understood that no linear relationship exists between the number of cells within an organism and the cancer incidence rate. To resolve what is known as Peto's Paradox, additional anticancer strategies within different species have to be postulated. These naturally occurring idiosyncrasies to avoid carcinogenesis represent novel potential therapeutic strategies.


Assuntos
Transmissão de Doença Infecciosa , Metabolismo Energético/fisiologia , Neoplasias/etiologia , Neoplasias/virologia , Animais , Bivalves , Carcinogênese , Cricetinae , Modelos Animais de Doenças , Cães , Humanos , Marsupiais , Neoplasias/prevenção & controle , Espécies Reativas de Oxigênio/metabolismo , Tumores Venéreos Veterinários
11.
Am J Physiol Endocrinol Metab ; 321(1): E146-E155, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34097543

RESUMO

Cannabinoid 1 receptor (CB1R) inverse agonists reduce body weight and improve several parameters of glucose homeostasis. However, these drugs have also been associated with deleterious side effects. CB1R expression is widespread in the brain and in peripheral tissues, but whether specific sites of expression can mediate the beneficial metabolic effects of CB1R drugs, while avoiding the untoward side effects, remains unclear. Evidence suggests inverse agonists may act on key sites within the central nervous system to improve metabolism. The ventromedial hypothalamus (VMH) is a critical node regulating energy balance and glucose homeostasis. To determine the contributions of CB1Rs expressed in VMH neurons in regulating metabolic homeostasis, we generated mice lacking CB1Rs in the VMH. We found that the deletion of CB1Rs in the VMH did not affect body weight in chow- and high-fat diet-fed male and female mice. We also found that deletion of CB1Rs in the VMH did not alter weight loss responses induced by the CB1R inverse agonist SR141716. However, we did find that CB1Rs of the VMH regulate parameters of glucose homeostasis independent of body weight in diet-induced obese male mice.NEW & NOTEWORTHY Cannabinoid 1 receptors (CB1Rs) regulate metabolic homeostasis, and CB1R inverse agonists reduce body weight and improve parameters of glucose metabolism. However, the cell populations expressing CB1Rs that regulate metabolic homeostasis remain unclear. CB1Rs are highly expressed in the ventromedial hypothalamic nucleus (VMH), which is a crucial node that regulates metabolism. With CRISPR/Cas9, we generated mice lacking CB1Rs specifically in VMH neurons and found that CB1Rs in VMH neurons are essential for the regulation of glucose metabolism independent of body weight regulation.


Assuntos
Peso Corporal/fisiologia , Glucose/metabolismo , Homeostase/fisiologia , Neurônios/metabolismo , Receptor CB1 de Canabinoide/fisiologia , Núcleo Hipotalâmico Ventromedial/metabolismo , Animais , Composição Corporal/fisiologia , Proteína 9 Associada à CRISPR , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Dieta Hiperlipídica , Metabolismo Energético/fisiologia , Feminino , Edição de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/etiologia , Obesidade/metabolismo , Receptor CB1 de Canabinoide/deficiência , Receptor CB1 de Canabinoide/genética
12.
FASEB J ; 35(7): e21708, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34169549

RESUMO

Metabolic reprogramming occurs in cancer cells and is regulated partly by the opposing actions of tyrosine kinases and tyrosine phosphatases. Several members of the protein tyrosine phosphatase (PTP) superfamily have been linked to cancer as either pro-oncogenic or tumor-suppressive enzymes. In order to investigate which PTPs can modulate the metabolic state of cancer cells, we performed an shRNA screen of PTPs in HCT116 human colorectal cancer cells. Among the 72 PTPs efficiently targeted, 24 were found to regulate mitochondrial respiration, 8 as negative and 16 as positive regulators. Of the latter, we selected TC-PTP (PTPN2) for further characterization since inhibition of this PTP resulted in major functional defects in oxidative metabolism without affecting glycolytic flux. Transmission electron microscopy revealed an increase in the number of damaged mitochondria in TC-PTP-null cells, demonstrating the potential role of this PTP in regulating mitochondrial homeostasis. Downregulation of STAT3 by siRNA-mediated silencing partially rescued the mitochondrial respiration defect observed in TC-PTP-deficient cells, supporting the role of this signaling axis in regulating mitochondrial activity. In addition, mitochondrial stress prevented an increased expression of electron transport chain-related genes in cells with TC-PTP silencing, correlating with decreased ATP production, cellular proliferation, and migration. Our shRNA-based metabolic screen revealed that PTPs can serve as either positive or negative regulators of cancer cell metabolism. Taken together, our findings uncover a new role for TC-PTP as an activator of mitochondrial metabolism, validating this PTP as a key target for cancer therapeutics.


Assuntos
Metabolismo Energético/fisiologia , Dinâmica Mitocondrial/fisiologia , Proteína Tirosina Fosfatase não Receptora Tipo 2/metabolismo , Tirosina/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Células HCT116 , Células HEK293 , Humanos , Fosforilação/fisiologia , Proteínas Tirosina Quinases/metabolismo , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/fisiologia
13.
Nutrients ; 13(6)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063868

RESUMO

The recent identification of brown adipose tissue in adult humans offers a new strategy to increase energy expenditure to treat obesity and associated metabolic disease. While white adipose tissue (WAT) is primarily for energy storage, brown adipose tissue (BAT) is a thermogenic organ that increases energy expenditure to generate heat. BAT is activated upon cold exposure and improves insulin sensitivity and lipid clearance, highlighting its beneficial role in metabolic health in humans. This review provides an overview of BAT physiology in conditions of overnutrition (obesity and associated metabolic disease), undernutrition and in conditions of altered fat distribution such as lipodystrophy. We review the impact of exercise, dietary macronutrients and bioactive compounds on BAT activity. Finally, we discuss the therapeutic potential of dietary manipulations or supplementation to increase energy expenditure and BAT thermogenesis. We conclude that chronic nutritional interventions may represent a useful nonpharmacological means to enhance BAT mass and activity to aid weight loss and/or improve metabolic health.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Metabolismo Energético/fisiologia , Desnutrição/fisiopatologia , Estado Nutricional/fisiologia , Hipernutrição/fisiopatologia , Exercício Físico/fisiologia , Humanos , Resistência à Insulina/fisiologia , Termogênese/fisiologia , Perda de Peso/fisiologia
14.
Nat Commun ; 12(1): 3525, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112797

RESUMO

Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons integrate pre-synaptic AgRP signaling, thereby modulating the post-synaptic serotonergic pathway. Specifically, the MC4RdlDRN signaling elicits profound, bi-directional, regulation of body weight mainly through sympathetic outflow that reprograms mitochondrial bioenergetics within brown and beige fat while feeding remains intact. Together, we suggest that this AgRP neural circuit plays a unique role in persistent control of energy expenditure and body weight, hinting next-generation therapeutic approaches for obesity and metabolic disorders.


Assuntos
Proteína Relacionada com Agouti/metabolismo , Metabolismo Energético/fisiologia , Hipotálamo/metabolismo , Condução Nervosa/fisiologia , Neurônios Serotoninérgicos/fisiologia , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Peso Corporal , Cromatografia Líquida , Ingestão de Alimentos/fisiologia , Metabolismo Energético/genética , Masculino , Camundongos , Condução Nervosa/efeitos dos fármacos , Condução Nervosa/efeitos da radiação , Obesidade/metabolismo , Optogenética , Receptor Tipo 4 de Melanocortina/genética , Receptor Tipo 4 de Melanocortina/metabolismo , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/efeitos da radiação , Serotonina/metabolismo , Serotonina/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Espectrometria de Massas em Tandem , Temperatura
15.
Nutrients ; 13(5)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066330

RESUMO

Consumption of fructose has been associated with a higher risk of developing obesity and metabolic syndrome (MetS). The aim of this study was to examine the long-term effects of fructose compared to starch from high-amylose maize starch (HiMaize) at ad libitum feeding in a juvenile Göttingen Minipig model with 20% of the diet provided as fructose as a high-risk diet (HR, n = 15) and 20% as HiMaize as a lower-risk control diet (LR, n = 15). The intake of metabolizable energy was on average similar (p = 0.11) among diets despite increased levels of the satiety hormone PYY measured in plasma (p = 0.0005) of the LR pigs. However, after over 20 weeks of ad libitum feeding, no difference between diets was observed in daily weight gain (p = 0.103), and a difference in BW was observed only at the end of the experiment. The ad libitum feeding promoted an obese phenotype over time in both groups with increased plasma levels of glucose (p = 0.005), fructosamine (p < 0.001), insulin (p = 0.03), and HOMA-IR (p = 0.02), whereas the clinical markers of dyslipidemia were unaffected. When compared to the LR diet, fructose did not accelerate the progression of MetS associated parameters and largely failed to change markers that indicate a stimulated de novo lipogenesis.


Assuntos
Dieta da Carga de Carboidratos/efeitos adversos , Ingestão de Energia/fisiologia , Frutose/administração & dosagem , Síndrome Metabólica/etiologia , Obesidade/etiologia , Animais , Biomarcadores/sangue , Dieta da Carga de Carboidratos/métodos , Modelos Animais de Doenças , Dislipidemias/sangue , Metabolismo Energético/fisiologia , Amido/administração & dosagem , Suínos , Porco Miniatura , Ganho de Peso/efeitos dos fármacos , Zea mays
16.
Int J Mol Sci ; 22(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069652

RESUMO

Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of obesity because it negatively modulates the hypothalamic control of food intake due to metaflammation and lipotoxicity. The use of animal models, such as rodents, in conjunction with in vitro models of hypothalamic cells, can enhance the understanding of hypothalamic functions related to the control of energy balance, thereby providing knowledge about the impact of diet on the hypothalamus, in addition to targets for the development of new drugs that can be used in humans to decrease body weight. Recently, sphingolipids were described as having a lipotoxic effect in peripheral tissues and the central nervous system. Specifically, lipid overload, mainly from long-chain saturated fatty acids, such as palmitate, leads to excessive ceramide levels that can be sensed by the hypothalamus, triggering the dysregulation of energy balance control. However, no systematic review has been undertaken regarding studies of sphingolipids, particularly ceramide and sphingosine-1-phosphate (S1P), the hypothalamus, and obesity. This review confirms that ceramides are associated with hypothalamic dysfunction in response to metaflammation, endoplasmic reticulum (ER) stress, and lipotoxicity, leading to insulin/leptin resistance. However, in contrast to ceramide, S1P appears to be a central satiety factor in the hypothalamus. Thus, our work describes current evidence related to sphingolipids and their role in hypothalamic energy balance control. Hypothetically, the manipulation of sphingolipid levels could be useful in enabling clinicians to treat obesity, particularly by decreasing ceramide levels and the inflammation/endoplasmic reticulum stress induced in response to overfeeding with saturated fatty acids.


Assuntos
Ceramidas/metabolismo , Metabolismo Energético/fisiologia , Ácidos Graxos/fisiologia , Animais , Ceramidas/fisiologia , Dieta Hiperlipídica/efeitos adversos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácidos Graxos/metabolismo , Humanos , Hipotálamo/metabolismo , Hipotálamo/fisiologia , Resistência à Insulina/fisiologia , Leptina/metabolismo , Lisofosfolipídeos/metabolismo , Obesidade/metabolismo , Transdução de Sinais/fisiologia , Esfingolipídeos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo
17.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065168

RESUMO

Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer's disease (AD). Late AD is associated with amyloid (Aß) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD/5xFAD), heterozygous (Tg5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aß plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD/- and Tg5xFAD/5xFAD mice and increased expression of IL-1ß in Tg5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD/- and Tg5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.


Assuntos
Doença de Alzheimer/metabolismo , Metabolismo Energético/fisiologia , Hipotálamo/metabolismo , Doenças Metabólicas/metabolismo , Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas Amiloidogênicas/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Polipeptídeo Inibidor Gástrico/metabolismo , Grelina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Insulina/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Placa Amiloide/metabolismo , Resistina/metabolismo
18.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065474

RESUMO

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/-) mice were constructed. Zfp217+/- mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/- mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/- mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/- mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/- mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.


Assuntos
Metabolismo Energético/fisiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Transativadores/metabolismo , Adipócitos Brancos/metabolismo , Adipócitos Brancos/fisiologia , Adipogenia/fisiologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/fisiopatologia , Animais , Dieta Hiperlipídica , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Termogênese/fisiologia , Ganho de Peso/fisiologia
19.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065591

RESUMO

Central and peripheral serotonin (5HT) have opposing functions in the regulation of energy homeostasis. Both increasing 5HT signaling in the brain and decreasing 5HT signaling in the periphery have been proposed as potential treatments for obesity. This study investigates the relationship between constitutionally high or low 5HT activity and systemic net energy balance. Two sublines of rats with high and low whole-body 5HT tone, obtained by selective breeding for platelet 5HT parameters, were examined for fat accumulation in different white adipose tissue (WAT) depots, glucose/insulin tolerance, blood metabolic parameters, and expression of various metabolic genes. High-5HT animals, unlike their low-5HT counterparts, developed widespread intra-abdominal obesity associated with glucose and insulin intolerance, which worsened with age. They also had elevated blood glucose and lipid parameters but showed no significant changes in circulating leptin, resistin, and adipsin levels. Surprisingly, adiponectin levels were increased in plasma but reduced in the WAT of high-5HT rats. A limited number of metabolic genes belonging to different functional classes showed differential expression in WAT of high-5HT compared to low-5HT rats. Overall, a constitutive increase in 5HT tone is associated with a positive energy balance acting through subtle dysregulation of a broad spectrum of metabolic pathways.


Assuntos
Homeostase/fisiologia , Serotonina/metabolismo , Adiponectina/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Encéfalo/metabolismo , Metabolismo Energético/fisiologia , Feminino , Insulina/metabolismo , Leptina/metabolismo , Lipídeos/fisiologia , Masculino , Obesidade/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia
20.
J Endocrinol ; 250(2): 67-79, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34014835

RESUMO

Bariatric surgery is still the most effective long-term weight-loss therapy. Recent data indicate that surgical outcomes may be affected by diurnal food intake patterns. In this study, we aimed to investigate how surgery-induced metabolic adaptations (i.e. weight loss) interact with circadian clock function. For that reason, vertical sleeve gastrectomy (VSG) was performed in obese mice and rhythms in behavior, tissue rhythmicity, and white adipose tissue transcriptome were evaluated. VSG under constant darkness conditions led to a maximum weight loss of 18% compared to a loss of 3% after sham surgery. Post-surgical weight development was characterized by two distinct intervals of catabolic and subsequent anabolic metabolic state. Locomotor activity was not affected. However, VSG significantly increased active phase meal frequency in the anabolic state. No significant effects on clock gene rhythmicity were detected in adrenal and white adipose tissue (WAT) explant cultures. Transcriptome rhythm analyses of subcutaneous WAT revealed a reduction of cycling genes after VSG (sham: 2493 vs VSG: 1013) independent of sustained rhythms in core clock gene expression. This may be a consequence of weight loss-induced morphological reconstruction of WAT that overwrites the direct influence of the local clock machinery on the transcriptome. However, VSG altered rhythmic transcriptional regulation of WAT lipid metabolism pathways. Thus, our data suggest a reorganization of diurnal metabolic rhythms after VSG downstream of the molecular clock machinery.


Assuntos
Cirurgia Bariátrica , Ritmo Circadiano/fisiologia , Obesidade/cirurgia , Perda de Peso , Animais , Comportamento Animal , Ritmo Circadiano/genética , Metabolismo Energético/fisiologia , Gastrectomia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Núcleo Supraquiasmático/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...