Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.619
Filtrar
1.
FASEB J ; 35(10): e21891, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34569666

RESUMO

In humans, insulin resistance has been linked to an impaired metabolic transition from fasting to feeding (metabolic flexibility; MetFlex). Previous studies suggest that mitochondrial dynamics response is a putative determinant of MetFlex; however, this has not been studied in humans. Thus, the aim of this study was to investigate the mitochondrial dynamics response in the metabolic transition from fasting to feeding in human peripheral blood mononuclear cells (PBMCs). Six male subjects fasted for 16 h (fasting), immediately after which they consumed a 75-g oral glucose load (glucose). In both fasting and glucose conditions, blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images. We exposed in vitro acetoacetate-treated PBMCs to the specific IP3R inhibitor Xestospongin B (XeB) to reduce IP3R-mediated mitochondrial Ca2+ accumulation. This allowed us to evaluate the role of ER-mitochondria Ca2+ exchange in the mitochondrial dynamic response to substrate availability. To determine whether PBMCs could be used in obesity context (low MetFlex), we measured mitochondrial dynamics in mouse spleen-derived lymphocytes from WT and ob/ob mice. We demonstrated that the transition from fasting to feeding reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs. In addition, we demonstrated that IP3R activity is key in the mitochondrial dynamics response when PBMCs are treated with a fasting-substrate in vitro. In murine mononuclear-cells, we confirmed that mitochondria-ER interactions are regulated in the fasted-fed transition and we further highlight mitochondria-ER miscommunication in PBMCs of diabetic mice. In conclusion, our results demonstrate that the fasting/feeding transition reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs, and that IP3R activity may potentially play a central role.


Assuntos
Sinalização do Cálcio , Ingestão de Alimentos , Jejum/metabolismo , Leucócitos Mononucleares/metabolismo , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Adulto , Animais , Glucose/administração & dosagem , Humanos , Masculino , Camundongos
2.
Nat Commun ; 12(1): 5058, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433808

RESUMO

Dietary interventions such as intermittent fasting (IF) have emerged as an attractive strategy for cancer therapies; therefore, understanding the underlying molecular mechanisms is pivotal. Here, we find SIRT7 decline markedly attenuates the anti-tumor effect of IF. Mechanistically, AMP-activated protein kinase (AMPK) phosphorylating SIRT7 at T263 triggers further phosphorylation at T255/S259 by glycogen synthase kinase 3ß (GSK3ß), which stabilizes SIRT7 by decoupling E3 ligase UBR5. SIRT7 hyperphosphorylation achieves anti-tumor activity by disrupting the SKP2-SCF E3 ligase, thus preventing SKP2-mediated K63-linked AKT polyubiquitination and subsequent activation. In contrast, GSK3ß-SIRT7 axis is inhibited by EGF/ERK2 signaling, with ERK2 inactivating GSK3ß, thus accelerating SIRT7 degradation. Unfavorably, glucose deprivation or chemotherapy hijacks the GSK3ß-SIRT7 axis via ERK2, thus activating AKT and ensuring survival. Notably, Trametinib, an FDA-approved MEK inhibitor, enhances the efficacy of combination therapy with doxorubicin and IF. Overall, we have revealed the GSK3ß-SIRT7 axis that must be fine-tuned in the face of the energetic and oncogenic stresses in malignancy.


Assuntos
Jejum/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Sirtuínas/metabolismo , Animais , Terapia Combinada , Doxorrubicina/administração & dosagem , Feminino , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Fosforilação , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteólise , Sirtuínas/genética
3.
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
4.
Am J Physiol Regul Integr Comp Physiol ; 321(3): R413-R428, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34260302

RESUMO

Elephant seals experience natural periods of prolonged food deprivation while breeding, molting, and undergoing postnatal development. Prolonged food deprivation in elephant seals increases circulating glucocorticoids without inducing muscle atrophy, but the cellular mechanisms that allow elephant seals to cope with such conditions remain elusive. We generated a cellular model and conducted transcriptomic, metabolic, and morphological analyses to study how seal cells adapt to sustained glucocorticoid exposure. Seal muscle progenitor cells differentiate into contractile myotubes with a distinctive morphology, gene expression profile, and metabolic phenotype. Exposure to dexamethasone at three ascending concentrations for 48 h modulated the expression of six clusters of genes related to structural constituents of muscle and pathways associated with energy metabolism and cell survival. Knockdown of the glucocorticoid receptor (GR) and downstream expression analyses corroborated that GR mediates the observed effects. Dexamethasone also decreased cellular respiration, shifted the metabolic phenotype toward glycolysis, and induced mitochondrial fission and dissociation of mitochondria-endoplasmic reticulum (ER) interactions without decreasing cell viability. Knockdown of DNA damage-inducible transcript 4 (DDIT4), a GR target involved in the dissociation of mitochondria-ER membranes, recovered respiration and modulated antioxidant gene expression in myotubes treated with dexamethasone. These results show that adaptation to sustained glucocorticoid exposure in elephant seal myotubes involves a metabolic shift toward glycolysis, which is supported by alterations in mitochondrial morphology and a reduction in mitochondria-ER interactions, resulting in decreased respiration without compromising cell survival.


Assuntos
Metabolismo Energético/fisiologia , Glucocorticoides/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Adaptação Fisiológica , Animais , Antioxidantes/metabolismo , Jejum/metabolismo , Privação de Alimentos/fisiologia , Fenótipo , Receptores de Glucocorticoides/genética , Focas Verdadeiras/metabolismo , Transcriptoma/fisiologia
5.
Neurology ; 97(9): e953-e963, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34233941

RESUMO

OBJECTIVE: To examine the feasibility, safety, systemic biological activity, and cerebral activity of a ketogenic dietary intervention in patients with glioma. METHODS: Twenty-five patients with biopsy-confirmed World Health Organization grade 2 to 4 astrocytoma with stable disease after adjuvant chemotherapy were enrolled in an 8-week Glioma Atkins-Based Diet (GLAD). GLAD consisted of 2 fasting days (calories <20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates ≤20 g/d) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, insulin-like growth factor-1, and magnetic resonance spectroscopy at baseline and week 8. RESULTS: Twenty-one patients (84%) completed the study. Eighty percent of patients reached ≥40 mg/dL urine acetoacetate during the study. Forty-eight percent of patients were adherent by food record. The diet was well tolerated, with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity, including hemoglobin A1c, insulin, and fat body mass, decreased significantly, while lean body mass increased. Magnetic resonance spectroscopy demonstrated increased ketone concentrations (ß-hydroxybutyrate [bHB] and acetone) in both lesional and contralateral brain compared to baseline. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB R s = 0.52, p = 0.05). Subgroup analysis of isocitrate dehydrogenase-mutant glioma showed no differences in cerebral metabolites after controlling for ketonuria. CONCLUSION: The GLAD dietary intervention, while demanding, produced meaningful ketonuria and significant systemic and cerebral metabolic changes in participants. Ketonuria in participants correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02286167.


Assuntos
Neoplasias Encefálicas/dietoterapia , Encéfalo/metabolismo , Dieta Rica em Proteínas e Pobre em Carboidratos/métodos , Dieta Cetogênica/métodos , Glioma/dietoterapia , Adulto , Idoso , Jejum/metabolismo , Estudos de Viabilidade , Feminino , Humanos , Cetose/metabolismo , Masculino , Pessoa de Meia-Idade
6.
J Biol Chem ; 297(1): 100884, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34146544

RESUMO

The mechanistic target of rapamycin (mTOR) is often referred to as a master regulator of the cellular metabolism that can integrate the growth factor and nutrient signaling. Fasting suppresses hepatic mTORC1 activity via the activity of the tuberous sclerosis complex (TSC), a negative regulator of mTORC1, to suppress anabolic metabolism. The loss of TSC1 in the liver locks the liver in a constitutively anabolic state even during fasting, which was suggested to regulate peroxisome proliferator-activated receptor alpha (PPARα) signaling and ketogenesis, but the molecular determinants of this regulation are unknown. Here, we examined if the activation of the mTORC1 complex in mice by the liver-specific deletion of TSC1 (TSC1L-/-) is sufficient to suppress PPARα signaling and therefore ketogenesis in the fasted state. We found that the activation of mTORC1 in the fasted state is not sufficient to repress PPARα-responsive genes or ketogenesis. Furthermore, we examined whether the activation of the anabolic program mediated by mTORC1 complex activation in the fasted state could suppress the robust catabolic programming and enhanced PPARα transcriptional response of mice with a liver-specific defect in mitochondrial long-chain fatty acid oxidation using carnitine palmitoyltransferase 2 (Cpt2L-/-) mice. We generated Cpt2L-/-; Tsc1L-/- double-KO mice and showed that the activation of mTORC1 by deletion of TSC1 could not suppress the catabolic PPARα-mediated phenotype of Cpt2L-/- mice. These data demonstrate that the activation of mTORC1 by the deletion of TSC1 is not sufficient to suppress a PPARα transcriptional program or ketogenesis after fasting.


Assuntos
Jejum/metabolismo , Fígado/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais , Proteína 1 do Complexo Esclerose Tuberosa/genética , Animais , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Deleção de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Proteína 1 do Complexo Esclerose Tuberosa/metabolismo
7.
Nutrients ; 13(5)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068302

RESUMO

BACKGROUND: research exploring the effects of food timing and frequency on health and disease is currently ongoing. While there is an increasing body of scientific literature showing the potential health benefits of intermittent fasting (IF) in laboratory settings and in animals, studies regarding IF on humans are limited. Therefore, the objective of this research was to evaluate the relationship between the feeding/fasting time window and metabolic outcomes among adult individuals. METHODS: dietary and demographic data of 1936 adult subjects living in the south of Italy were examined. Food frequency questionnaires (FFQ) were administered to determine the period of time between the first and the last meal of a typical day. Subjects were then divided into those with a time feeding window lasting more than 10 h, within 8 h (TRF-8) and within 10 h. RESULTS: after adjustment for potential confounding factors related to eating habits (such as adherence to the Mediterranean diet, having breakfast/dinner), TRF-10 was inversely associated with being overweight/obese (OR = 0.05, 95% CI: 0.01, 0.07), hypertension (OR = 0.24, 95% CI: 0.13, 0.45), and dyslipidemias (OR = 0.26, 95% CI: 0.10, 0.63), while TRF-8 only with being overweight/obese (OR = 0.08, 95% CI: 0.04, 0.15) and hypertension (OR = 0.33, 95% CI: 0.17, 0.60). No associations were found with type-2 diabetes. CONCLUSIONS: individuals with a restricted feeding time window were less likely to be overweight, obese and hypertensive. Further studies are needed to clearly validate the results of the present study.


Assuntos
Jejum/metabolismo , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Dieta Mediterrânea , Dislipidemias/epidemiologia , Comportamento Alimentar , Feminino , Humanos , Hipertensão/epidemiologia , Itália , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Obesidade/epidemiologia , Fatores de Tempo
8.
Nat Commun ; 12(1): 3660, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135321

RESUMO

The mechanistic target of rapamycin complex 1 (mTORC1) integrates cellular nutrient signaling and hormonal cues to control metabolism. We have previously shown that constitutive nutrient signaling to mTORC1 by means of genetic activation of RagA (expression of GTP-locked RagA, or RagAGTP) in mice resulted in a fatal energetic crisis at birth. Herein, we rescue neonatal lethality in RagAGTP mice and find morphometric and metabolic alterations that span glucose, lipid, ketone, bile acid and amino acid homeostasis in adults, and a median lifespan of nine months. Proteomic and metabolomic analyses of livers from RagAGTP mice reveal a failed metabolic adaptation to fasting due to a global impairment in PPARα transcriptional program. These metabolic defects are partially recapitulated by restricting activation of RagA to hepatocytes, and revert by pharmacological inhibition of mTORC1. Constitutive hepatic nutrient signaling does not cause hepatocellular damage and carcinomas, unlike genetic activation of growth factor signaling upstream of mTORC1. In summary, RagA signaling dictates dynamic responses to feeding-fasting cycles to tune metabolism so as to match the nutritional state.


Assuntos
Jejum/metabolismo , Fígado/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Transdução de Sinais , Animais , Modelos Animais de Doenças , Glucose/metabolismo , Homeostase , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Proteínas Monoméricas de Ligação ao GTP/genética , Nutrientes/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Fenótipo , Proteômica , Transdução de Sinais/efeitos dos fármacos , Sirolimo/administração & dosagem , Sirolimo/farmacologia , Transcrição Genética/efeitos dos fármacos , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa/metabolismo
9.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067001

RESUMO

Investigations into the mechanisms regulating obesity are frantic and novel translational approaches are needed. The raccoon dog (Nyctereutes procyonoides) is a canid species representing a promising model to study metabolic regulation in a species undergoing cycles of seasonal obesity and fasting. To understand the molecular mechanisms of metabolic regulation in seasonal adaptation, we analyzed key central nervous system and peripheral signals regulating food intake and metabolism from raccoon dogs after autumnal fattening and winter fasting. Expressions of neuropeptide Y (NPY), orexin-2 receptor (OX2R), pro-opiomelanocortin (POMC) and leptin receptor (ObRb) were analyzed as examples of orexigenic and anorexigenic signals using qRT-PCR from raccoon dog hypothalamus samples. Plasma metabolic profiles were measured with 1H NMR-spectroscopy and LC-MS. Circulating hormones and cytokines were determined with canine specific antibody assays. Surprisingly, NPY and POMC were not affected by the winter fasting nor autumn fattening and the metabolic profiles showed a remarkable equilibrium, indicating conserved homeostasis. However, OX2R and ObRb expression changes suggested seasonal regulation. Circulating cytokine levels were not increased, demonstrating that the autumn fattening did not induce subacute inflammation. Thus, the raccoon dog developed seasonal regulatory mechanisms to accommodate the autumnal fattening and prolonged fasting making the species unique in coping with the extreme environmental challenges.


Assuntos
Adiposidade , Jejum/metabolismo , Metaboloma , Cães Guaxinins/metabolismo , Estações do Ano , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal , Análise Discriminante , Feminino , Hormônios/sangue , Hipotálamo/metabolismo , Inflamação/patologia , Análise dos Mínimos Quadrados , Limite de Detecção , Análise Multivariada , Peptídeos/genética , Peptídeos/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Cães Guaxinins/sangue , Receptores de Peptídeos/metabolismo
10.
Fish Physiol Biochem ; 47(4): 1119-1132, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34057672

RESUMO

This study was conducted to assess the impacts of prolonged fasting (70 and 120 days) on the morphological, biochemical, oxidative stress responses, immune-related gene expression, histopathology, and DNA damage in rainbow trout. Final weight (FW), hepatosomatic index (HSI), and condition factor (CF) significantly decreased in both 70 and 120 days of fasting compared to the pre-fasting group (p < 0.05). Fasting led to a significant reduction in serum blood metabolites (glucose, total protein, triglyceride, T. cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)) and endogenous reserves (protein and lipid). However, plasma acetylcholinesterase (AChE) activity, aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin (IL1), tumor necrosis factor (TNF1α), and transferrin (TF) increased significantly (p < 0.05). While malondialdehyde (MDA) levels compared to the pre-fasting group increased in the liver and muscle tissues (70 and 120 days), glutathione (GSH) enzyme activities decreased significantly in both tissues (p < 0.05). Histopathologically, both fasting groups (70 and 120 days) when compared to the pre-fasting group led to steatosis, necrosis and degeneration in hepatocytes, inflammation and hyperemia in the liver tissue and hyaline degeneration, atrophy, and inflammation in muscle tissue. Additionally, 8-OHdG levels of the liver and muscle tissues at 120 days' fasting were more severe according to 70 days' fasting. Finally, blood, the liver, and muscle tissues may be helpful to assess the impacts of fasting and fasting stress in rainbow trout.


Assuntos
Jejum/metabolismo , Oncorhynchus mykiss , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Acetilcolinesterase/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Dano ao DNA , Proteínas de Peixes/genética , Expressão Gênica , Glutationa/metabolismo , Interleucina-1/genética , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Músculos/metabolismo , Músculos/patologia , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/crescimento & desenvolvimento , Oncorhynchus mykiss/imunologia , Oncorhynchus mykiss/metabolismo , Estresse Oxidativo , Transferrina/genética , Fator de Necrose Tumoral alfa/genética
11.
Online braz. j. nurs. (Online) ; 20: e20216480, 05 maio 2021. ilus
Artigo em Inglês, Espanhol, Português | LILACS, BDENF - Enfermagem | ID: biblio-1224134

RESUMO

OBJETIVO: Identificar na produção científica a ocorrência de alterações metabólicas no pós-operatório de cirurgias eletivas e sua relação com o tempo de jejum no pré-operatório. MÉTODO: Revisão integrativa, realizada de junho a julho de 2020 nas bases de dados LILACS, MEDLINE, CINAHL, COCHRANE, SCOPUS e EMBASE. Foram selecionados artigos de 2015 a 2020. Para a análise dos níveis de evidência seguiu-se a categorização de Oxford Centre for Evidence-Based Medicine. RESULTADOS: Foram selecionados 10 artigos científicos. As alterações metabólicas encontradas foram hiperglicemia, elevação dos níveis séricos de IL-6, cortisol e valina, aumento da resistência insulínica, queda dos níveis plasmáticos de ácido glutâmico e elevação dos níveis de IGF-1 com a redução de IGFBP-3. A abreviação do tempo de jejum minimiza o estresse orgânico ao paciente, com a redução das alterações metabólicas, tempo de internação e morbidade. CONCLUSÃO: O tempo de jejum pré-operatório superior a oito horas está relacionado a ocorrência de alterações metabólicas no pós-operatório. As cirurgias de grande porte apresentam as maiores alterações metabólicas.


OBJECTIVE: To identify in the scientific production the occurrence of metabolic changes in the postoperative period of elective surgeries and their relation with preoperative fasting time. METHOD: An integrative review carried out from June to July 2020 in the LILACS, MEDLINE, CINAHL, COCHRANE, SCOPUS, and EMBASE databases. Articles from 2015 to 2020 were selected. For the analysis of the evidence levels, the Oxford Centre for Evidence-Based Medicine categorization was followed. RESULTS: A total of 10 scientific articles were selected. The metabolic changes found were hyperglycemia, elevated serum levels of IL-6, cortisol, and valine, increased insulin resistance, decreased glutamic acid plasma levels, and increased IGF-1 levels with a reduction of IGFBP-3. Shortening the fasting time minimizes the patient's organic stress, with a reduction of metabolic changes, hospitalization time and morbidity. CONCLUSION: Preoperative fasting time longer than eight hours is related to metabolic changes in the postoperative period. Major surgeries present the greatest metabolic changes.


OBJETIVO: Identificar en la producción científica la existencia de cambios metabólicos en el postoperatorio de cirugías electivas y su relación con el tiempo de ayuno en el período preoperatorio. MÉTODO: Revisión integradora, realizada de junio a julio de 2020 de las bases de datos LILACS, MEDLINE, CINAHL, COCHRANE, SCOPUS y EMBASE. Se seleccionaron artículos de 2015 a 2020. Para el análisis de los niveles de evidencia se siguió la categorización del Oxford Center for Evidence-Based Medicine. RESULTADOS: Se seleccionaron 10 artículos científicos. Las alteraciones metabólicas encontradas fueron hiperglucemia, niveles séricos elevados de IL-6, cortisol y valina, aumento de la resistencia a la insulina, reducción de los niveles plasmáticos de ácido glutámico y aumento de los niveles de IGF-1 con disminución de IGFBP-3. La disminución del tiempo de ayuno minimiza el estrés orgánico del paciente, con una reducción de los cambios metabólicos, la duración de la estancia hospitalaria y la morbilidad. CONCLUSIÓN: Existe una relación entre un tiempo de ayuno preoperatorio mayor a ocho horas y la presencia de cambios metabólicos en el postoperatorio. Las cirugías mayores muestran los mayores cambios metabólicos.


Assuntos
Humanos , Período Pós-Operatório , Jejum/metabolismo , Procedimentos Cirúrgicos Eletivos , Período Pré-Operatório , Pacientes Internados
12.
Diabetes Res Clin Pract ; 175: 108835, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33901626

RESUMO

The IDF-DAR guidance was most recently updated this year. The most notable change is the moving to a scoring system from a tabulated risk categorization to determine and classify the risk of harm from fasting derived from an online survey. This change may be appealing and is welcomed. However, such a system and the methodology underpinning it is not without limitations. This commentary highlights some of these limitations and the associated limited safe options available to individuals with diabetes desiring to fast during Ramadan. Overlooked clinical considerations that deserve formal recognition include the role of technology (aspects relating to glucose monitoring and/or insulin delivery) and previous experience of safe Ramadan fasting. Further, duration of fast (which can almost double in temperate regions from winter to summer) needs greater emphasis. We also advocate separate scoring systems for people with type 1 diabetes and complex type 2 diabetes. The guidance acknowledges fasting is an individual's decision, however the general message needs to be more person-centred and currently only presents a binary approach to fasting - all or nothing choices. We propose and discuss addition options including, trial fasting of voluntary fasts, starting the fast and terminating due to health and/or safety, intermittent fasting and winter fasting.


Assuntos
Automonitorização da Glicemia/métodos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Jejum/metabolismo , Hipoglicemiantes/uso terapêutico , Feminino , Humanos , Hipoglicemiantes/farmacologia , Islamismo , Masculino
13.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806756

RESUMO

The popularity of fasting and restricted food intake is increasing. While the body's adaptability to dietary insufficiency is crucial for health, molecular mechanisms of adaptive changes are not well understood. Here, we compared the effects of fasting and exercise on the expression of leukocyte genes and proteins involved in the storage, export, and acquisition of iron, an essential element with physiological roles. Healthy men participated in the study (age, 30-70 years; body weight, 60-100 kg; body mass index, 20-29.9 kg/m2). The participants performed an exercise test with a gradually increasing intensity until the individual maximum exercise capacity was reached, before and after 8-d fast. Blood samples were collected before, immediately after, and 3 h after exercise. Gene expression was analyzed by reverse-transcription quantitative polymerase chain reaction and protein levels were analyzed by immunobloting. Eight days of total starvation diet affected the body composition and decreased exercise capacity. Further, fasting decreased the expression of genes associated with iron storage and export, and increased the expression of genes involved in iron acquisition. Conversely, only PCBP2 protein increased after fasting; however, an upward trend was apparent for all proteins. In conclusion, the body adapts to starvation by adjusting iron economy.


Assuntos
Proteínas de Transporte de Cátions/genética , Jejum , Regulação da Expressão Gênica , Ferro/metabolismo , Leucócitos/metabolismo , Adulto , Proteínas de Transporte de Cátions/metabolismo , Jejum/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Fatores Sexuais , Fatores de Tempo
14.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806354

RESUMO

The loss of skeletal muscle mass (muscle atrophy or wasting) caused by aging, diseases, and injury decreases quality of life, survival rates, and healthy life expectancy in humans. Although long non-coding RNAs (lncRNAs) have been implicated in skeletal muscle formation and differentiation, their precise roles in muscle atrophy remain unclear. In this study, we used RNA-sequencing (RNA-Seq) to examine changes in the expression of lncRNAs in four muscle atrophy conditions (denervation, casting, fasting, and cancer cachexia) in mice. We successfully identified 33 annotated lncRNAs and 18 novel lncRNAs with common expression changes in all four muscle atrophy conditions. Furthermore, an analysis of lncRNA-mRNA correlations revealed that several lncRNAs affected small molecule biosynthetic processes during muscle atrophy. These results provide novel insights into the lncRNA-mediated regulatory mechanism underlying muscle atrophy and may be useful for the identification of promising therapeutic targets.


Assuntos
Atrofia Muscular/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Animais , Caquexia/genética , Modelos Animais de Doenças , Regulação para Baixo , Jejum/metabolismo , Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Denervação Muscular , Músculo Esquelético/metabolismo , Atrofia Muscular/etiologia , RNA-Seq , Restrição Física , Regulação para Cima
15.
Nutrients ; 13(5)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33924911

RESUMO

Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects' blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4+ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4+ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4+ T cell immune responsiveness.


Assuntos
Proteínas Sanguíneas/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Jejum/metabolismo , Inflamação/sangue , Nutrientes/sangue , Obesidade/sangue , Adulto , Idoso , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Adulto Jovem
16.
Biochim Biophys Acta Mol Cell Res ; 1868(6): 119017, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33741434

RESUMO

BACKGROUND: Fasting changes mitochondrial function, and mTOR acts as a major regulator of mitochondrial energy production ensuring the survival under reduced supply of nutrition. This study assessed the role of protein arginine methyltransferase 1 (PRMT1), which regulates mitochondrial function, in the context of fasting. METHODS: The effect of fasting on mTOR signaling and mTOR-regulated mitochondrial mass was assessed in LO2 cells (in vitro) and C57BL/6J mice (in vivo). Biochemical parameters of fasting were determined in blood samples of mice. PRMT1 expression was investigated by transfecting LO2 cells with an expression vector. Gene expression was determined by real-time quantitative PCR, protein interaction by chromatin immunoprecipitation, protein expression by Western blotting and immunofluorescence microscopy, and the mitochondrial mass by MitoTracker staining. RESULTS: After 48 h of fasting, mTOR and PRMT1 expression, as well as mitochondrial mass, were significantly reduced in LO2 cells, and in liver tissue sections. Fasting downregulated the expression of miR-21 and upregulated the expression of its target phosphatase and tensin homolog (PTEN), which was responsible for reduced mTOR expression. Inhibition of mTOR reduced phosphorylation of STAT1, and thereby PRMT1 expression in LO2 cells. Low PRMT1 down-regulated the expression of peroxisome proliferator-activated receptor (PPAR)-γ and thereby decreased mitochondrial mass. Supplementation of insulin contracted the effect of fasting on all mentioned parameters. CONCLUSIONS: Fasting downregulates miR-21 and increases its target PTEN, thereby inhibiting mTOR signaling, p-STAT1, PRMT1, and mitochondrial mass. These findings highlight the role of mTOR and PRMT1 in the regulation of cellular energy availability.


Assuntos
Jejum/sangue , Hepatócitos/citologia , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT1/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular , Jejum/metabolismo , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Mitocôndrias Hepáticas/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação
17.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33723074

RESUMO

Fasting in mammals promotes increases in circulating glucagon and decreases in circulating insulin that stimulate catabolic programs and facilitate a transition from glucose to lipid burning. The second messenger cAMP mediates effects of glucagon on fasting metabolism, in part by promoting the phosphorylation of CREB and the dephosphorylation of the cAMP-regulated transcriptional coactivators (CRTCs) in hepatocytes. In Drosophila, fasting also triggers activation of the single Crtc homolog in neurons, via the PKA-mediated phosphorylation and inhibition of salt-inducible kinases. Crtc mutant flies are more sensitive to starvation and oxidative stress, although the underlying mechanism remains unclear. Here we use RNA sequencing to identify Crtc target genes that are up-regulated in response to starvation. We found that Crtc stimulates a subset of fasting-inducible genes that have conserved CREB binding sites. In keeping with its role in the starvation response, Crtc was found to induce the expression of genes that inhibit insulin secretion (Lst) and insulin signaling (Impl2). In parallel, Crtc also promoted the expression of genes involved in one-carbon (1-C) metabolism. Within the 1-C pathway, Crtc stimulated the expression of enzymes that encode modulators of S-adenosyl-methionine metabolism (Gnmt and Sardh) and purine synthesis (ade2 and AdSl) Collectively, our results point to an important role for the CREB/CRTC pathway in promoting energy balance in the context of nutrient stress.


Assuntos
Proteínas de Drosophila/genética , Metabolismo Energético , Jejum/metabolismo , Insulina/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Animais , Carbono/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas de Drosophila/metabolismo , Regulação Enzimológica da Expressão Gênica , Ligação Proteica , Estresse Fisiológico , Fatores de Transcrição/metabolismo
18.
Endocrinology ; 162(8)2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33720335

RESUMO

Deiodinases modify the biological activity of thyroid hormone (TH) molecules, ie, they may activate thyroxine (T4) to 3,5,3'-triiodothyronine (T3), or they may inactivate T3 to 3,3'-diiodo-L-thyronine (T2) or T4 to reverse triiodothyronine (rT3). Although evidence of deiodination of T4 to T3 has been available since the 1950s, objective evidence of TH metabolism was not established until the 1970s. The modern paradigm considers that the deiodinases not only play a role in the homeostasis of circulating T3, but they also provide dynamic control of TH signaling: cells that express the activating type 2 deiodinase (D2) have enhanced TH signaling due to intracellular build-up of T3; the opposite is seen in cells that express type 3 deiodinase (D3), the inactivating deiodinase. D2 and D3 are expressed in metabolically relevant tissues such as brown adipose tissue, skeletal muscle and liver, and their roles have been investigated using cell, animal, and human models. During development, D2 and D3 expression customize for each tissue/organ the timing and intensity of TH signaling. In adult cells, D2 is induced by cyclic adenosine monophosphate (cAMP), and its expression is invariably associated with enhanced T3 signaling, expression of PGC1 and accelerated energy expenditure. In contrast, D3 expression is induced by hypoxia-inducible factor 1α (HIF-1a), dampening T3 signaling and the metabolic rate. The coordinated expression of these enzymes adjusts TH signaling in a time- and tissue-specific fashion, affecting metabolic pathways in health and disease states.


Assuntos
Iodeto Peroxidase/metabolismo , Hormônios Tireóideos/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Jejum/metabolismo , Humanos
19.
Nutrients ; 13(2)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33673009

RESUMO

Asprosin is a recently discovered protein released during fasting conditions mainly by adipocytes from white adipose tissue. As a glucogenic peptide, it stimulates the release of glucose from hepatic cells by binding to the OLFR734 receptor and leading to the activation of the G protein-cAMP-PKA pathway. As it crosses the blood-brain barrier, it also acts as an orexigenic peptide that stimulates food intake through activation of AgRP neurons in the hypothalamus; thus, asprosin participates in maintaining the body's energy homeostasis. Moreover, studies have shown that asprosin levels are pathologically elevated in obesity and related diseases. However, the administration of anti-asprosin antibodies can both normalize its concentration and reduce food intake in obese mice, which makes it an interesting factor to combat obesity and related diseases. Current research also draws attention to the relationship between asprosin and fertility, especially in men. Asprosin improves age- and obesity-related decrease in fertility potential by improving sperm motility. It should also be mentioned that plasma asprosin levels can be differentially modulated by physical activity; intense anaerobic exercise increases asprosin level, while aerobic exercise decreases it. However, further research is necessary to confirm the exact mechanisms of asprosin activity and its potential as a therapeutic target.


Assuntos
Adipocinas/fisiologia , Diabetes Mellitus/metabolismo , Fibrilina-1/fisiologia , Infertilidade/metabolismo , Obesidade/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Jejum/metabolismo , Feminino , Glucose/metabolismo , Homeostase/fisiologia , Humanos , Masculino , Camundongos , Camundongos Obesos , Transdução de Sinais/fisiologia , Motilidade Espermática/fisiologia
20.
AAPS PharmSciTech ; 22(3): 84, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649887

RESUMO

Prediction of performance of traditional, reformulated, and novel oral formulations in adults and pediatrics is of great importance. This study was conducted to assess solubility of celecoxib in age-appropriate fasted- and fed-state gastric and intestinal biorelevant media, classify celecoxib into biopharmaceutical classification system (BCS), and assess the effects of age-related developmental changes in the composition and volume of gastrointestinal fluids on the solubility and performance of oral formulations containing celecoxib. Solubility of celecoxib was assessed at 37°C in the pH range specified by the BCS-based criteria in 13 age-appropriate biorelevant media reflective of the gastric and proximal small intestinal environment in both fasted and fed states in adults and different pediatric subpopulations. A validated HPLC-UV method was used to quantify celecoxib. Experimental and computational molecular descriptors and in vivo pharmacokinetic data were used to assign the permeability class of celecoxib. Celecoxib belonged to BCS class 2. The pediatric to adult solubility ratios were outside the 80-125% boundaries in 3 and borderline in 1 biorelevant media. Significant age-related variability could be predicted for oral formulations containing celecoxib intended for pediatric use. Findings of this study indicated that the criteria used in the adult BCS might not be directly applied to pediatric subpopulations.


Assuntos
Produtos Biológicos/classificação , Produtos Biológicos/farmacocinética , Celecoxib/classificação , Celecoxib/farmacocinética , Jejum/metabolismo , Absorção Gastrointestinal/fisiologia , Administração Oral , Adulto , Anti-Inflamatórios não Esteroides/classificação , Anti-Inflamatórios não Esteroides/farmacocinética , Líquidos Corporais/química , Líquidos Corporais/metabolismo , Criança , Pré-Escolar , Avaliação Pré-Clínica de Medicamentos/métodos , Previsões , Absorção Gastrointestinal/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Permeabilidade , Solubilidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...