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1.
Life Sci ; 242: 117182, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31863770

RESUMO

AIMS: The present study was designed to compare the effects of a low-fat diet (LF), calorie restriction (CR), quercetin (Que) and exercise (Ex) on hepatic steatosis in a high-fat (HF) diet-induced obesity prone (OP) model in the perspective of microRNA (miR)-dependent thyroid hormone (TH) synthesis and action. MAIN METHODS: Male C57BL/6J mice were administered a HF diet for 10 weeks to induce OP phenotype and then divided into 5 groups, HF diet (OP-HF), LF diet (OP-LF), 70% CR (OP-CR), 0.05% Que (OP-Que) and a treadmill exercise regimen (OP-Ex); one additional group fed LF diet served as control (LF). 7 weeks later, serum indexes, metabolic alterations, redox status and histological appearance in the thyroid and liver, and TH related miRs with their targets expressions were determined. KEY FINDINGS: No significance on T3 levels was observed among the six groups. LF, CR, Que and Ex significantly ameliorated HF-induced hepatic steatosis to varying degrees, inhibited T4 production via differentially elevating miR-339, miR-383 and miR-146b to decrease NIS expression and regulating miR-200a/Nrf2 to maintain redox status in the thyroid. Furthermore, these four interventions differentially and significantly decreased miR-383 and miR-146b to elevate TRb and DIO1 expression, and subsequent TH responsive lipid metabolism genes regulation. Among them, the effects of CR on hepatic steatosis were the most prominent. SIGNIFICANCE: Our data indicated that amelioration of hepatic steatosis by LF, CR, Que and Ex resulted in many shared, but also many differential changes in the miR-dependent TH production and action.


Assuntos
Dieta com Restrição de Gorduras , Fígado Gorduroso/terapia , MicroRNAs/fisiologia , Obesidade/complicações , Condicionamento Físico Animal , Hormônios Tireóideos/metabolismo , Animais , Restrição Calórica , Fígado Gorduroso/dietoterapia , Fígado Gorduroso/etiologia , Hipolipemiantes/uso terapêutico , Lipídeos/análise , Fígado/química , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Estresse Oxidativo , Quercetina/uso terapêutico
2.
Gene ; 725: 144191, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31654705

RESUMO

Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decrease mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. However, the detailed mechanisms of immunomodulation by CR remain unclear. In this study, we established a mouse model for CR and analyzed the changes of immune cells in these mice. The CR mice fed a calorie-restricted diet for 4 weeks had lower body weight and fat mass compared with control mice. The proportions of CD4+, CD8+, and naïve CD4+ T cells in spleen cells from CR mice were higher than those in of control mice. Additionally, the proportion of CD8+ T cells was significantly decreased and the mRNA expression of proinflammatory cytokines in the colon of CR mice was significantly decreased compared with those of control mice. To determine the effect of CR on microRNA (miRNA) expression, serum and tissues were collected from mice and the expression level of miRNA was analyzed by real-time RT-PCR. As a result, the expressions of miR-16-5p, miR-196b-5p, and miR-218-5p in serum from CR mice were higher than those in control mice. The expression of miR-16-5p increased in the spleen, thymus, colon, and stomach of CR mice compared with expression in control mice. Furthermore, RAW264 cells transfected with a miR-16-5p mimic significantly decreased the mRNA expression of IL-1ß, IL-6, and TNF-α under LPS stimulation. These results suggested that miR-16-5p might be a critical factor involving the anti-inflammatory effects of calorie-restricted feeding.


Assuntos
Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Envelhecimento/metabolismo , Animais , Restrição Calórica/métodos , Citocinas/genética , Citocinas/metabolismo , Dietoterapia , Inflamação/metabolismo , Interleucina-1beta/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Células RAW 264.7 , Ativação Transcricional , Fator de Necrose Tumoral alfa/genética , Regulação para Cima
3.
JAMA ; 322(15): 1486-1499, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613346

RESUMO

Importance: High-quality dietary patterns may help prevent chronic disease, but limited data exist from randomized trials about the effects of nutritional and behavioral interventions on dietary changes. Objective: To assess the effect of a nutritional and physical activity education program on dietary quality. Design, Setting, and Participants: Preliminary exploratory interim analysis of an ongoing randomized trial. In 23 research centers in Spain, 6874 men and women aged 55 to 75 years with metabolic syndrome and no cardiovascular disease were enrolled in the trial between September 2013 and December 2016, with final data collection in March 2019. Interventions: Participants were randomized to an intervention group that encouraged an energy-reduced Mediterranean diet, promoted physical activity, and provided behavioral support (n = 3406) or to a control group that encouraged an energy-unrestricted Mediterranean diet (n = 3468). All participants received allotments of extra-virgin olive oil (1 L/mo) and nuts (125 g/mo) for free. Main Outcomes and Measures: The primary outcome was 12-month change in adherence based on the energy-reduced Mediterranean diet (er-MedDiet) score (range, 0-17; higher scores indicate greater adherence; minimal clinically important difference, 1 point). Results: Among 6874 randomized participants (mean [SD] age, 65.0 [4.9] years; 3406 [52%] men), 6583 (96%) completed the 12-month follow-up and were included in the main analysis. The mean (SD) er-MedDiet score was 8.5 (2.6) at baseline and 13.2 (2.7) at 12 months in the intervention group (increase, 4.7 [95% CI, 4.6-4.8]) and 8.6 (2.7) at baseline and 11.1 (2.8) at 12 months in the control group (increase, 2.5 [95% CI, 2.3-2.6]) (between-group difference, 2.2 [95% CI, 2.1-2.4]; P < .001). Conclusions and Relevance: In this preliminary analysis of an ongoing trial, an intervention that encouraged an energy-reduced Mediterranean diet and physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significantly greater increase in diet adherence after 12 months. Further evaluation of long-term cardiovascular effects is needed. Trial Registration: isrctn.com Identifier: ISRCTN89898870.


Assuntos
Restrição Calórica , Dieta Mediterrânea , Exercício , Síndrome Metabólica/dietoterapia , Cooperação do Paciente , Idoso , Doenças Cardiovasculares/prevenção & controle , Inquéritos sobre Dietas , Feminino , Educação em Saúde , Humanos , Modelos Lineares , Lipídeos/sangue , Masculino , Síndrome Metabólica/terapia , Pessoa de Meia-Idade , Obesidade/dietoterapia , Fatores de Risco , Espanha
4.
J Int Soc Sports Nutr ; 16(1): 36, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477138

RESUMO

BACKGROUND: Variations in the fat mass and obesity-associated gene (FTO) are associated with obesity; however, it is unclear if changes in energy intake affect the adaptive response to caloric restriction in those with risk variants. The three FTO single nucleotide polymorphisms (SNPs), rs1421085, rs17817449 and rs9939609, are in strong linkage disequilibrium. Thus, the purpose of this investigation was to determine the role of these FTO SNPs vis-à-vis the effects of a 4-week hypocaloric diet on body composition in exercise-trained men and women. Two salivary biomarkers that associate with energy expenditure were also assessed (cortisol and salivary alpha-amylase, sAA). METHODS: Forty-seven exercise-trained men (n = 11) and women (n = 36) (mean ± SD: age 32 ± 9 years; height 169 ± 8 cm, body mass index 24.5 ± 2.9 kg/m2, hours of aerobic training per week 4.9 ± 3.8, hours of weight training per week 3.9 ± 2.4, years of training experience 13.4 ± 7.0) completed a 4-week hypocaloric diet (i.e., decrease total calories by ~ 20-25% while maintaining a protein intake of ~ 2.0 g/kg/d). Subjects were instructed to maintain the same training regimen and to decrease energy intake via carbohydrate and/or fat restriction during the treatment period. Body composition was assessed via dual-energy X-ray absorptiometry (DXA) (Model: Hologic Horizon W; Hologic Inc., Danbury CT USA). Total body water was determined via a multifrequency bioelectrical impedance (BIA) device (InBody 770). Saliva samples were collected pre and post intervention in order to genotype the participants as well as to determine the concentrations of cortisol and sAA. RESULTS: Of the 47 subjects, 15 were of normal risk for obesity whereas 32 were carriers of the FTO gene risk alleles. Subjects were grouped based on their genotype for the three FTO SNPs (i.e., rs1421085, rs17817449 and rs9939609) due to their strong linkage disequilibrium. We have classified those with the normal obesity risk as "non-risk allele" versus those that carry the "risk allele" (i.e., both heterozygous and homozygous). Both groups experienced a significant decrease in total energy intake (p < 0.01); non-risk allele: pre kcal 2081 ± 618, post kcal 1703 ± 495; risk allele: pre kcal 1886 ± 515, post kcal 1502 ± 366). Both groups lost a significant amount of body weight (p < 0.01); however, there was no difference between groups for the change (post minus pre) in each group (risk allele change: - 1.0 ± 1.2 kg, non-risk allele change: - 1.2 ± 1.4 kg). Additionally, both groups lost a significant amount of fat mass (p < 0.01) with no differences between groups for the change in fat mass (risk allele change for fat mass: 1.1 ± 0.7 kg, non-risk allele change - 0.9 ± 0.4 kg). There were no significant changes in either group for fat free mass or total body water. The change in salivary alpha-amylase or cortisol was not different between groups. CONCLUSIONS: In the short-term (i.e., 4 weeks), exercise-trained men and women consuming a hypocaloric diet that is relatively high in protein experience similar changes in body composition due exclusively to a decrement in fat mass and independent of FTO allele status. Therefore, weight and fat loss on a hypocaloric diet is, at least in the short-term, unaffected by the FTO gene.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Restrição Calórica , Exercício , Adulto , Alelos , Composição Corporal , Ingestão de Energia , Feminino , Humanos , Desequilíbrio de Ligação , Masculino , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adulto Jovem
5.
Adv Exp Med Biol ; 1178: 113-127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493225

RESUMO

Both morbidity and mortality due to cardiovascular diseases (CVDs) elevate with age. The elevated prevalence of cardiovascular risk factors with age and cardiovascular aging contribute to the relationship between aging and CVDs. Dietary restriction (DR) consisting of calorie restriction (CR) and alternate-day fasting (ADF) is an approved nutritional intervention and shows anti-aging impacts. Recent studies demonstrate that DR makes an active defense response in stressful states. At the core of this response are cardiovascular protective signals, which consist of the mammalian target of rapamycin (mTOR), AMP-activated kinase, sirtuins and endothelial nitric oxide synthase. These make a network with positive and negative feedback regulation. Hence, DR is a hopeful intervention for controlling cardiovascular aging and managing individuals with CVDs.


Assuntos
Restrição Calórica , Doenças Cardiovasculares , Jejum , Envelhecimento/fisiologia , Doenças Cardiovasculares/dietoterapia , Humanos
6.
World J Gastroenterol ; 25(27): 3590-3606, 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31367159

RESUMO

BACKGROUND: Obesity is a major risk factor for a variety of diseases such as diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction (CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction (LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear. AIM: To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota. METHODS: We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet (ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57BL/6 mice received fecal microbiota transplantation (FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet (HFD) ad libitum for 16 wk. Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing. RESULTS: We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND (28.71 ± 0.29 vs 28.05 ± 0.15, P < 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFD-fed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight (44.95 ± 1.02 vs 40.53 ± 0.97, P < 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota. CONCLUSION: Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.


Assuntos
Restrição Calórica , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/terapia , Extratos Vegetais/administração & dosagem , Animais , Terapia Combinada/métodos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Microbioma Gastrointestinal/fisiologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Obesidade/etiologia , Obesidade/microbiologia , Resultado do Tratamento
7.
Radiat Res ; 192(4): 451-455, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31390311

RESUMO

Calorie restriction is known to influence several physiological processes and to alleviate the late effects of radiation exposure such as neoplasm induction and life shortening. However, earlier related studies were limited to acute radiation exposure. Therefore, in this study we examined the influence of chronic low-dose-rate irradiation on lifespan. Young male B6C3F1/Jcl mice were divided randomly into two groups, which were fed either a low-calorie (65 kcal/ week) or high-calorie (95 kcal/week) diet. The latter is comparable to ad libitum feeding. The animals in the irradiated group were continuously exposed to gamma rays for 400 days at 20 mGy/day, resulting in a total dose of 8 Gy. Exposure and calorie restriction were initiated at 8 weeks of age and the diets were maintained for life. The life-shortening effects from chronic whole-body irradiation were compared between the groups. Body weights were reduced in calorie-restricted mice irrespective of radiation treatment. Radiation induced a shortened median lifespan in both groups, but to a greater extent in the calorie-restricted mice. These results suggest that calorie restriction may sensitize mice to chronic low-dose-rate radiation exposure to produce a life-shortening effect rather than alleviating the effects of radiation.


Assuntos
Restrição Calórica , Longevidade/efeitos da radiação , Doses de Radiação , Animais , Raios gama/efeitos adversos , Masculino , Camundongos , Modelos de Riscos Proporcionais , Fatores de Tempo
8.
Eat Behav ; 34: 101309, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31325801

RESUMO

Restrained eaters tend to sustain a restriction in caloric intake to lose or maintain body weight; however, only a few restrained eaters can achieve the goal of restricting their caloric intake to lose or maintain body weight. Those who are effective restrained eaters habitually adhere to their intentions to avoid eating certain palatable foods, whereas those who are ineffective restrained eaters are generally unable to translate their intentions into behavior. To restrain eating regardless of temptation, an individual must first identify potential conflicts between achieving restrained eating and temptation to eat. Regarding food selections, the association between a lack of conflict between temptation, eating enjoyment, and weight loss or maintenance goals and the failure of restriction of caloric intake remains unknown. The present study used an eye-tracking technique to assess the degree of conflict experienced by effective and ineffective restrained eaters during food choice. Participants were required to choose between pairs of high- and low-calorie foods. The results showed that choosing the low-calorie food was associated with the experience of more conflict, measured by longer response times and more gaze switches, than choosing the high-calorie food. Ineffective restrained eaters experienced less conflict, exhibiting shorter response times and fewer gaze switches, than did effective restrained eaters, which suggests that a failure to restrain eating might be associated with a lack of experience of conflict.


Assuntos
Dieta/psicologia , Ingestão de Alimentos/psicologia , Ingestão de Energia/fisiologia , Comportamento Alimentar/psicologia , Adulto , Peso Corporal , Restrição Calórica/psicologia , Emoções , Feminino , Alimentos , Preferências Alimentares/psicologia , Humanos , Motivação , Tempo de Reação , Perda de Peso/fisiologia , Adulto Jovem
9.
J Immunol Res ; 2019: 2015892, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31321243

RESUMO

Caloric restriction mimetics (CRMs), compounds that mimic the biochemical effects of nutrient deprivation, administered via systemic route promote antitumor effects through the induction of autophagy and the modulation of the immune microenvironment; however, collateral effects due to metabolic changes and the possible weight loss might potentially limit their administration at long term. Here, we investigated in mice local administration of CRMs via aerosol to reduce metastasis implantation in the lung, whose physiologic immunosuppressive status favors tumor growth. Hydroxycitrate, spermidine, and alpha-lipoic acid, CRMs that target different metabolic enzymes, administered by aerosol, strongly reduced implantation of intravenously injected B16 melanoma cells without overt signs of toxicity, such as weight loss and changes in lung structure. Cytofluorimetric analysis of lung immune infiltrates revealed a significant increase of alveolar macrophages and CD103+ dendritic cells in mice treated with CRMs that paralleled an increased recruitment and activation of both CD3 T lymphocytes and NK cells. These effects were associated with the upregulation of genes related to M1 phenotype, as IL-12 and STAT-1, and to the decrease of M2 genes, as IL-10 and STAT-6, in adherent fraction of lung immune infiltrate, as revealed by real-time PCR analysis. Thus, in this proof-of-principle study, we highlight the antitumor effect of CRM aerosol delivery as a new and noninvasive therapeutic approach to locally modulate immunosurveillance at the tumor site in the lung.


Assuntos
Restrição Calórica , Citratos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Espermidina/uso terapêutico , Ácido Tióctico/uso terapêutico , Animais , Antígenos CD/imunologia , Células Dendríticas/imunologia , Cadeias alfa de Integrinas/imunologia , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Monitorização Imunológica , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT6/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Microambiente Tumoral/imunologia
10.
Fish Shellfish Immunol ; 92: 637-648, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271836

RESUMO

This study investigated the effects of restricted feeding on the growth performance, oxidative stress and inflammation of Megalobrama amblycephala fed high-carbohydrate (HC) diets. Fish (46.94 ±â€¯0.04 g) were randomly assigned to four groups containing the satiation of a control diet (30% carbohydrate) and three satiate levels (100% (HC1), 80% (HC2) and 60% (HC3)) of the HC diets (43% carbohydrate) for 8 weeks. Results showed that HC1 diet remarkably decreased final weight (FW), weight gain rate (WGR), specific growth rate (SGR), feed conversion ratio (FCR), hepatic activities of total anti-oxidation capacity (T-AOC), superoxide dismutase (SOD) and catalase (CAT), the AMP/ATP ratio, the p-AMPKα/t-AMPKα ratio, sirtuin-1 (SIRT1) protein expression and hepatic transcriptions of AMPKα2, SIRT1, nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT), manganese superoxide dismutase (Mn-SOD), glutathione peroxidase 1 (GPx1) and interleukin10 (IL 10) compared to the control group, whereas the opposite was true for protein efficiency ratio (PER), nitrogen retention efficiency (NRE), energy retention efficiency (ERE), plasma glucose levels, alanine transaminase (AST) and aspartate aminotransferase (ALT) activities, hepatic contents of malondialdehyde (MDA), tumour necrosis factor α (TNF α) and interleukin 1ß (IL 1ß), ATP and AMP contents and hepatic transcriptions of kelch-like ECH associating protein 1 (Keap1), IkB kinase α (IKK α), nuclear factor kappa B (NF-κB), TNF α, IL 1ß, interleukin 6 (IL 6) and transforming growth factor ß (TGF ß). As for the HC groups, fish fed the HC2 diet obtained relatively high values of SGR, PER, NRE, ERE, hepatic activities of T-AOC, SOD and CAT, the AMP/ATP ratio, the p-AMPKα/t-AMPKα ratio, SIRT1 protein expression and hepatic transcriptions of AMPKα2, Nrf2, CAT, copper/zinc superoxide dismutase (Cu/Zn-SOD), Mn-SOD, GPx1, glutathione S-transferase (GST) and interleukin10 (IL 10), while the opposite was true for hepatic content of IL 6 and transcription of IKK α. Overall, an 80% satiation improved the growth performance and alleviated the oxidative stress and inflammation of blunt snout bream fed HC diets via the activation of the AMPK-SIRT1 pathway and the up-regulation of the activities and transcriptions of Nrf2-modulated antioxidant enzymes coupled with the depression of the levels and transcriptions of the NF-κB-mediated pro-inflammatory cytokines.


Assuntos
Restrição Calórica/veterinária , Cyprinidae/imunologia , Carboidratos da Dieta/metabolismo , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Ração Animal/análise , Animais , Cyprinidae/metabolismo , Dieta/veterinária , Distribuição Aleatória , Sirtuína 1/metabolismo
11.
Nutrients ; 11(7)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277506

RESUMO

The reversion of diabetes and the treatment of long-term obesity are difficult challenges. The failure mechanisms of rapid weight loss are mainly related to the wasting of lean mass. This single-arm study aims to evaluate the effects of a very low-calorie ketogenic diet (VLCKD) on body composition and resting energy expenditure in the short term reversal of diabetes mellitus Type 2. For eight weeks, subjects were administered a personalized VLCKD with protein intake based on lean mass and synthetic amino acidic protein supplementation. Each subject was assessed by anthropometry, Dual-energy X-ray Absorptiometry(DXA), bioimpedentiometric analysis (BIA), indirect calorimetry, and biochemical analysis. The main findings were the saving of lean mass, the reduction of abdominal fat mass, restored metabolic flexibility, the maintenance of resting energy expenditure, and the reversion of diabetes. These results highlight how the application of preventive, predictive, personalized, and participative medicine to nutrition may be promising for the prevention of diabetes and enhancement of obesity treatment.


Assuntos
Gordura Abdominal/fisiopatologia , Adiposidade , Restrição Calórica , Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos , Dieta Cetogênica , Metabolismo Energético , Gordura Abdominal/diagnóstico por imagem , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Ingestão de Energia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Perda de Peso
12.
Curr Sports Med Rep ; 18(7): 258-265, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31283626

RESUMO

A significant percentage of the population is classified as obese, and there is a growing need to develop novel therapy to reduce body weight. It has long been appreciated that caloric restriction and exercise are the cornerstones of any weight loss method. This review outlines the challenges faced when attempting to achieve weight loss and the metabolic adaptations that ensue upon reductions in body weight which make sustaining weight loss extremely difficult. We discuss the need for novel approaches to weight loss that would increase basal metabolic rate and counter the biological adaptations that provide barriers for maintaining weight reduction. We introduce two metabolic processes, hypobaric hypoxia and cold exposure, which, when activated, cause increased metabolic rate even in the presence of reduced caloric intake. While we do not suggest that these are long-term viable options for methods to achieve weight loss, we are introducing these as pathways that may be targeted to eventually develop novel therapies to achieve sustainable weight loss.


Assuntos
Metabolismo Basal , Obesidade/terapia , Perda de Peso , Tecido Adiposo Bege/fisiologia , Restrição Calórica , Temperatura Baixa , Homeostase , Humanos , Hipóxia , Músculo Esquelético/fisiologia , Termogênese
13.
PLoS Comput Biol ; 15(7): e1007162, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31269015

RESUMO

The evolutionarily conserved nature of the few well-known anti-aging interventions that affect lifespan, such as caloric restriction, suggests that aging-related research in model organisms is directly relevant to human aging. Since human lifespan is a complex trait, a systems-level approach will contribute to a more comprehensive understanding of the underlying aging landscape. Here, we integrate evolutionary and functional information of normal aging across human and model organisms at three levels: gene-level, process-level, and network-level. We identify evolutionarily conserved modules of normal aging across diverse taxa, and notably show proteostasis to be conserved in normal aging. Additionally, we find that mechanisms related to protein quality control network are enriched for genes harboring genetic variants associated with 22 age-related human traits and associated to caloric restriction. These results demonstrate that a systems-level approach, combined with evolutionary conservation, allows the detection of candidate aging genes and pathways relevant to human normal aging.


Assuntos
Envelhecimento/metabolismo , Proteostase , Adulto , Idoso , Envelhecimento/genética , Animais , Caenorhabditis elegans , Restrição Calórica , Biologia Computacional , Drosophila melanogaster , Evolução Molecular , Feminino , Perfilação da Expressão Gênica , Marcadores Genéticos , Humanos , Longevidade/genética , Longevidade/fisiologia , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Biológicos , Proteostase/genética , Especificidade da Espécie , Adulto Jovem
14.
Nutrients ; 11(8)2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31357685

RESUMO

Here we aimed at determining the therapeutic effect of a very low-calorie diet in overweight episodic migraine patients during a weight-loss intervention in which subjects alternated randomly between a very low-calorie ketogenic diet (VLCKD) and a very low-calorie non-ketogenic diet (VLCnKD) each for one month. In a nutritional program, 35 overweight obese migraine sufferers were allocated blindly to 1-month successive VLCKD or VLCnKD in random order (VLCKD-VLCnKD or VLCnKD-VLCD). The primary outcome measure was the reduction of migraine days each month compared to a 1-month pre-diet baseline. Secondary outcome measures were 50% responder rate for migraine days, reduction of monthly migraine attacks, abortive drug intake and body mass index (BMI) change. Only data from the intention-to-treat cohort (n = 35) will be presented. Patients who dropped out (n = 6) were considered as treatment failures. Regarding the primary outcome, during the VLCKD patients experienced -3.73 (95% CI: -5.31, -2.15) migraine days respect to VLCnKD (p < 0.0001). The 50% responder rate for migraine days was 74.28% (26/35 patients) during the VLCKD period, but only 8.57% (3/35 patients) during VLCnKD. Migraine attacks decreased by -3.02 (95% CI: -4.15, -1.88) during VLCKD respect to VLCnKD (p < 0.00001). There were no differences in the change of acute anti-migraine drug consumption (p = 0.112) and BMI (p = 0.354) between the 2 diets. A VLCKD has a preventive effect in overweight episodic migraine patients that appears within 1 month, suggesting that ketogenesis may be a useful therapeutic strategy for migraines.


Assuntos
Restrição Calórica , Dieta Cetogênica , Transtornos de Enxaqueca/dietoterapia , Sobrepeso/dietoterapia , Adulto , Analgésicos/uso terapêutico , Índice de Massa Corporal , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/fisiopatologia , Sobrepeso/diagnóstico , Sobrepeso/fisiopatologia , Roma , Fatores de Tempo , Resultado do Tratamento , Perda de Peso
15.
Nutrients ; 11(7)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252598

RESUMO

OBJECTIVE: The aim of the study was to compare the impact of 6 weeks of reducing daily caloric intake by 20% of total daily energy expenditure (TDEE)-CRI vs. reducing daily caloric intake by 30% of TDEE-CRII on body mass reduction and insulin metabolism in former athletes. METHODS: 94 males aged 35.7 ± 5.3 years, height 180.5 ± 4.1 cm, and body mass 96.82 ± 6.2 kg were randomly assigned to the CRI (n = 49) or CRII (n = 45) group. Thirty-one participants (18 subjects from CRI and 13 from CRII) resigned from the study. The effects of both diets on the body composition variables (body mass-BM; body fat-BF; fat free mass-FFM; muscle mass-MM; total body water-TBW), lipid profile (total lipids-TL; total cholesterol-TCh; HDL cholesterol-HDL; LDL cholesterol-LDL; triglycerides-TG), and glucose control variables (glucose-GL, insulin-I, HOMA-IR, insulin-like growth factor-1-IGF-1, leptin and adiponectin) were measured. RESULTS: After adhering to the CR I diet, significant differences were observed in FFM, MM and TG. After adhering to the CR II diet, significant differences were registered in tCh, TL and LDL. Both diets had a significant influence on leptin and adiponectin concentrations. Significant differences in FFM, MM, and tCh were observed between the CR I and CR II groups. At the end of the dietary intervention, significant differences in BF, FFM, MM and TBW were observed between the CR I and CR II groups. CONCLUSION: The 6 weeks of CR II diet appeared to be more effective in reducing BF and lipid profile and proved to be especially suitable for subjects with high body fat content and an elevated level of lipoproteins and cholesterol. Both reductive diets were effective in improving the levels of leptin and adiponectin in obese former athletes.


Assuntos
Atletas , Composição Corporal , Restrição Calórica , Lipídeos/sangue , Obesidade/dietoterapia , Perda de Peso , Adiponectina/sangue , Adiposidade , Adulto , Biomarcadores/sangue , Humanos , Leptina/sangue , Masculino , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
16.
Life Sci Alliance ; 2(4)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31253655

RESUMO

Dietary restriction (DR) increases life span through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of Caenorhabditis elegans subjected to DR. Transcription of muscle regulatory and structural genes increased, whereas increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level of translation. Evaluation of posttranscriptional regulation identified putative roles for RNA-binding proteins, RNA editing, miRNA, alternative splicing, and nonsense-mediated decay in response to nutrient limitation. Using RNA interference, we discovered several differentially expressed genes that regulate life span. We also found a compensatory role for translational regulation, which offsets dampened expression of a large subset of transcriptionally down-regulated genes. Furthermore, 3' UTR editing and intron retention increase under DR and correlate with diminished translation, whereas trans-spliced genes are refractory to reduced translation efficiency compared with messages with the native 5' UTR. Finally, we find that smg-6 and smg-7, which are genes governing selection and turnover of nonsense-mediated decay targets, are required for increased life span under DR.


Assuntos
Caenorhabditis elegans/genética , Restrição Calórica , Longevidade/genética , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas , Processamento Alternativo , Aminoácidos/metabolismo , Animais , Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica , Íntrons/genética , MicroRNAs/metabolismo , Proteínas Musculares/metabolismo , Neuropeptídeos/metabolismo , Biossíntese de Proteínas/genética , Interferência de RNA , RNA Mensageiro/metabolismo , Motivos de Ligação ao RNA , Telomerase/metabolismo , Transcriptoma
17.
Eat Weight Disord ; 24(4): 705-714, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165446

RESUMO

PURPOSE: A growing body of literature has established that food and alcohol disturbance (FAD: decreasing one's caloric intake in preparation for alcohol consumption) is a specific health risk that endangers health and wellbeing. Recent research on trends in FAD has revealed ethno-racial disparities. A sociological analysis is helpful to center race and examine the role of ethnic identity in reproducing health disparities. The current study is guided by theories of socialization into ideal body types by race. METHODS: Study uses data from a cross-sectional survey conducted among college students. The sample includes White and Black American college students, ages 18-25, and uses ordinal logistic regression to test for the impact of race and ethnic identity on engagement in FAD using the Compensatory Eating and Behaviors in Response to Alcohol Consumption Scale (CEBRACS). RESULTS: FAD prevalence was lower among Black Americans than among White Americans in the sample. Results from ordered logistic regression models indicate that stronger ethnic ties reduce likelihood of FAD among Black Americans but have the opposite effect among White Americans. This modification effect provides evidence that ethnic identity belonging protects against FAD for Black Americans but acts as a risk factor for FAD among White Americans. CONCLUSIONS: Findings shed light on the documented racial disparities in FAD and weight control behavior more broadly. Ethnic identity modifies the relationship between race and FAD in our sample. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Adolescente , Adulto , Afro-Americanos , Restrição Calórica , Estudos Transversais , Grupo com Ancestrais do Continente Europeu , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Masculino , Prevalência , Adulto Jovem
18.
Food Funct ; 10(6): 3581-3588, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31161182

RESUMO

The prevalence of obesity and its related metabolic syndrome (MetS) has shown an upsurge in recent years due to modified lifestyle patterns. The present study was designed to investigate the impact of a nutritionally balanced conventional meal replacement diet with modified macromolecular composition (rich in soy/pea protein and soluble fibers) and caloric restriction on Taiwanese obese subjects. Obese subjects (BMI > 27; n = 50, male 23, female 27) were recruited and requested to replace two meals per day (breakfast and lunch or dinner) with the balanced nutritional meal replacement diet (equal to 240 kcal) for 8 weeks with one regular meal and make sure that the daily target calorie limit (caloric restriction) was less than 1500 kcal day-1 for men and 1200 kcal day-1 for women. After eight weeks of intervention with a calorie-restricted balanced partial meal replacement diet, the levels of body weight, body fat, and waist circumference were significantly reduced by 4.1 kg, 2.38%, and 5.06 cm, respectively. The levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-c) were significantly decreased (p < 0.05) with a significant increase (p < 0.05) in high-density lipoprotein cholesterol (HDL-c) levels after 8 weeks of intervention with the meal replacement diet. Moreover, the levels of insulin, homeostatic model assessment-insulin resistance (HOMA-IR), leptin, thiobarbituric acid reactive substances (TBARS) and cardiovascular risk factors were significantly attenuated (p < 0.05). To conclude, the present intervention with meal replacement and caloric restriction on obese subjects could concomitantly decrease the body weight and glycemic and cardiovascular risk factors and thereby lower the risk of various metabolic disorders.


Assuntos
Obesidade/dietoterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Restrição Calórica , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Dieta Redutora , Ingestão de Energia , Feminino , Humanos , Insulina/metabolismo , Resistência à Insulina , Leptina/metabolismo , Masculino , Refeições , Pessoa de Meia-Idade , Obesidade/metabolismo , Adulto Jovem
19.
Genet Sel Evol ; 51(1): 27, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31195962

RESUMO

BACKGROUND: Selection of mice for decreased environmental variability of birth weight has achieved higher survivability and larger litter size as a correlated response to canalized selection, which suggests higher welfare and robustness, and animals that are more homogeneous. However, in these studies, animals were not exposed to an environmental challenge. To demonstrate the advantages of this mouse line with a low environmental variability of birth weight, animals from two divergent lines (high and low variability of birth weight) were subjected to feed restriction. The objective of this study was to use these divergent lines to compare their response in terms of robustness against an environmental challenge. At weaning, 120 females, i.e. four full-sib females from 10 random litters of three consecutive generations of selection, were chosen from these divergent lines. The total number of females was divided into four groups, which were subjected to a feeding regimen by imposing different levels of feed restriction (i.e. 75, 90 and 85% of full ad libitum feed across three generations, respectively) in different combinations during the growth and reproduction periods. RESULTS: Animals from the "low" line were less sensitive to a change in feed level than those from the "high" line. Regarding reproduction, the "low" line performed better in terms of number of females having parturitions, number of parturitions, and litter size. Imposing a feed restriction on female mice during their growth period did not affect the birth weight of their pups. The "low" line was preferred because of its higher reproductive efficiency and survival under an environmental challenge. CONCLUSIONS: Selection for decreased environmental variability of birth weight produces animals that are less sensitive to environmental conditions, which can be interpreted as having greater robustness.


Assuntos
Variação Biológica da População , Peso ao Nascer , Restrição Calórica , Seleção Genética , Animais , Meio Ambiente , Feminino , Especiação Genética , Masculino , Camundongos , Seleção Artificial
20.
Vasc Endovascular Surg ; 53(6): 470-476, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31216949

RESUMO

BACKGROUND: Open vascular surgery interventions are not infrequently hampered by complication rates and durability. Preclinical surgical models show promising beneficial effects in modulating the host response to surgical injury via short-term dietary preconditioning. Here, we explore short-term protein-calorie restriction preconditioning in patients undergoing elective carotid endarterectomy to understand patient participation dynamics and practicalities of robust research approaches around nutritional/surgical interventions. METHODS: We designed a pilot prospective, multicenter, randomized controlled study in patients undergoing carotid endarterectomy. After a 3:2 randomization to a 3-day preoperative protein-calorie restriction regimen (30% calorie/70% protein restriction) or ad libitum group, blood, clinical parameters, and stool samples were collected at baseline, pre-op, and post-op days 1 and 30. Subcutaneous and perivascular adipose tissues were harvested periprocedurally. Samples were analyzed for standard chemistries and cell counts, adipokines. Bacterial DNA isolation and 16S rRNA sequencing were performed on stool samples and the relative abundance of bacterial species was measured. RESULTS: Fifty-one patients were screened, 9 patients consented to the study, 5 were randomized, and 4 completed the trial. The main reason for non-consent was a 3-day in-hospital stay. All 4 participants were randomized to the protein-calorie restriction group, underwent successful endarterectomy, reported no compliance difficulties, nor were there adverse events. Stool analysis trended toward increased abundance of the sulfide-producing bacterial species Bilophila wadsworthia after dietary intervention (P = .08). CONCLUSIONS: Although carotid endarterectomy patients held low enthusiasm for a 3-day preoperative inpatient stay, there were no adverse effects in this small cohort. Multidisciplinary longitudinal research processes were successfully executed throughout the nutritional/surgical intervention. Future translational endeavors into dietary preconditioning of vascular surgery patients should focus on outpatient approaches.


Assuntos
Restrição Calórica , Estenose das Carótidas/cirurgia , Dieta com Restrição de Proteínas , Endarterectomia das Carótidas , Cuidados Pré-Operatórios/métodos , Idoso , Bilophila/crescimento & desenvolvimento , Boston , Restrição Calórica/efeitos adversos , Estenose das Carótidas/diagnóstico por imagem , Dieta com Restrição de Proteínas/efeitos adversos , Procedimentos Cirúrgicos Eletivos , Endarterectomia das Carótidas/efeitos adversos , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Estado Nutricional , Projetos Piloto , Cuidados Pré-Operatórios/efeitos adversos , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
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