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1.
Nat Commun ; 12(1): 565, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495474

RESUMO

Accumulating evidence indicates that obesity with its associated metabolic dysregulation, including hyperinsulinemia and aberrant circadian rhythms, increases the risk for a variety of cancers including postmenopausal breast cancer. Caloric restriction can ameliorate the harmful metabolic effects of obesity and inhibit cancer progression but is difficult to implement and maintain outside of the clinic. In this study, we aim to test a time-restricted feeding (TRF) approach on mouse models of obesity-driven postmenopausal breast cancer. We show that TRF abrogates the obesity-enhanced mammary tumor growth in two orthotopic models in the absence of calorie restriction or weight loss. TRF also reduces breast cancer metastasis to the lung. Furthermore, TRF delays tumor initiation in a transgenic model of mammary tumorigenesis prior to the onset of obesity. Notably, TRF increases whole-body insulin sensitivity, reduces hyperinsulinemia, restores diurnal gene expression rhythms in the tumor, and attenuates tumor growth and insulin signaling. Importantly, inhibition of insulin secretion with diazoxide mimics TRF whereas artificial elevation of insulin through insulin pumps implantation reverses the effect of TRF, suggesting that TRF acts through modulating hyperinsulinemia. Our data suggest that TRF is likely to be effective in breast cancer prevention and therapy.


Assuntos
Neoplasias da Mama/prevenção & controle , Modelos Animais de Doenças , Jejum , Hiperinsulinismo/prevenção & controle , Obesidade/prevenção & controle , Pós-Menopausa/fisiologia , Animais , Neoplasias da Mama/sangue , Neoplasias da Mama/fisiopatologia , Restrição Calórica/métodos , Linhagem Celular Tumoral , Dieta Hiperlipídica , Feminino , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/fisiopatologia , Resistência à Insulina/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/sangue , Obesidade/fisiopatologia , Ovariectomia , Pós-Menopausa/sangue
2.
Cochrane Database Syst Rev ; 1: CD013496, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33512717

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. Lifestyle changes are at the forefront of preventing the disease. This includes advice such as increasing physical activity and having a healthy balanced diet to reduce risk factors. Intermittent fasting (IF) is a popular dietary plan involving restricting caloric intake to certain days in the week such as alternate day fasting and periodic fasting, and restricting intake to a number of hours in a given day, otherwise known as time-restricted feeding. IF is being researched for its benefits and many randomised controlled trials have looked at its benefits in preventing CVD. OBJECTIVES: To determine the role of IF in preventing and reducing the risk of CVD in people with or without prior documented CVD. SEARCH METHODS: We conducted our search on 12 December 2019; we searched CENTRAL, MEDLINE and Embase. We also searched three trials registers and searched the reference lists of included papers. Systematic reviews were also viewed for additional studies. There was no language restriction applied. SELECTION CRITERIA: We included randomised controlled trials comparing IF to ad libitum feeding (eating at any time with no specific caloric restriction) or continuous energy restriction (CER). Participants had to be over the age of 18 and included those with and without cardiometabolic risk factors. Intermittent fasting was categorised into alternate-day fasting, modified alternate-day fasting, periodic fasting and time-restricted feeding. DATA COLLECTION AND ANALYSIS: Five review authors independently selected studies for inclusion and extraction. Primary outcomes included all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure. Secondary outcomes include the absolute change in body weight, and glucose. Furthermore, side effects such as headaches and changes to the quality of life were also noted. For continuous data, pooled mean differences (MD) (with 95% confidence intervals (CIs)) were calculated. We contacted trial authors to obtain missing data. We used GRADE to assess the certainty of the evidence.  MAIN RESULTS: Our search yielded 39,165 records after the removal of duplicates. From this, 26 studies met our criteria, and 18 were included in the pooled analysis. The 18 studies included 1125 participants and observed outcomes ranging from four weeks to six months. No studies included data on all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure at any point during follow-up. Of quantitatively analysed data, seven studies compared IF with ab libitum feeding, eight studies compared IF with CER, and three studies compared IF with both ad libitum feeding and CER. Outcomes were reported at short term (≤ 3 months) and medium term (> 3 months to 12 months) follow-up. Body weight was reduced with IF compared to ad libitum feeding in the short term (MD -2.88 kg, 95% CI -3.96 to -1.80; 224 participants; 7 studies; low-certainty evidence). We are uncertain of the effect of IF when compared to CER in the short term (MD -0.88 kg, 95% CI -1.76 to 0.00; 719 participants; 10 studies; very low-certainty evidence) and there may be no effect in the medium term (MD -0.56 kg, 95% CI -1.68 to 0.56; 279 participants; 4 studies; low-certainty evidence). We are uncertain about the effect of IF on glucose when compared to ad libitum feeding in the short term (MD -0.03 mmol/L, 95% CI -0.26 to 0.19; 95 participants; 3 studies; very-low-certainty of evidence) and when compared to CER  in the short term: MD -0.02 mmol/L, 95% CI -0.16 to 0.12; 582 participants; 9 studies; very low-certainty; medium term: MD 0.01, 95% CI -0.10 to 0.11; 279 participants; 4 studies; low-certainty evidence). The changes in body weight and glucose were not deemed to be clinically significant. Four studies reported data on side effects, with some participants complaining of mild headaches. One study reported on the quality of life using the RAND SF-36 score. There was a modest increase in the physical component summary score. AUTHORS' CONCLUSIONS: Intermittent fasting was seen to be superior to ad libitum feeding in reducing weight. However, this was not clinically significant. There was no significant clinical difference between IF and CER in improving cardiometabolic risk factors to reduce the risk of CVD. Further research is needed to understand the safety and risk-benefit analysis of IF in specific patient groups (e.g. patients with diabetes or eating disorders) as well as the effect on longer-term outcomes such as all-cause mortality and myocardial infarction.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Jejum , Adulto , Viés , Glicemia/metabolismo , Peso Corporal , Restrição Calórica/métodos , Jejum/efeitos adversos , Comportamento Alimentar , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Fatores de Tempo
3.
Rev Med Suisse ; 17(720-1): 59-62, 2021 Jan 13.
Artigo em Francês | MEDLINE | ID: mdl-33443833

RESUMO

The management of obesity comprises lifestyle changes targeting nutrient content, eating behavior and regular physical activity. Medication (orlistat, liraglutide) and bariatric surgery can later be used, but they require a clear indication and a close follow-up. Studies in chronobiology are now exploring the metabolic benefits of intermittent fasting, which restricts food intake and calorie-containing beverages to a certain window of the 24h cycle, or to certain days of the week/month, thus reinstating the alternance between anabolism and catabolism. However, the current scientific evidence is limited by the sample size and duration of the studies. It is therefore too early for a blanket strategy based on intermittent fasting in all patients with metabolic disorders.


Assuntos
Restrição Calórica/métodos , Jejum/fisiologia , Doenças Metabólicas/dietoterapia , Programas de Redução de Peso/métodos , Humanos , Obesidade/dietoterapia , Perda de Peso
5.
Life Sci ; 256: 117978, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32553927

RESUMO

AIMS: The mechanism of physical activity and calorie restriction remedying non-alcoholic fatty liver disease (NAFLD) remains elusive. The purpose of this study is to explore the effects of eccentric exercise and dietary regulation allied or alone on high-fat diet (HFD) induced NAFLD and its potential mechanism. MATERIALS AND METHODS: Mice were fed with HFD for 12 weeks and subsequently treated with chronic downhill running and caloric restriction for 8 weeks. Related biochemical index were examined both before and during intervention to evaluate the liver injury and dyslipidemia. Levels of MCP1, TNFα, IL-1ß, IL-6 and IL-10 were detected by ELISA. Liver morphology was observed by H&E and oil red O staining. Protein contents of iNOS, Arg-1, IL-1ß and IL-10 were determined by Western blot. CD86 and CD206 fluorescence were determined by Immunofluorescence. KEY FINDING: (1) 12 weeks' HFD induced hyperlipemia and hepatic steatosis by activating M1 macrophages phenotype and inhibiting M2 macrophages. (2) Chronic downhill running and caloric restriction promoted liver M2 macrophages phenotype, and inhibited M1 macrophages, to attenuate chronic inflammation and ameliorate hepatic steatosis. (3) The effects of downhill running and dietary regulation allied were more effective on improving NAFLD compared with downhill running or caloric restriction alone. SIGNIFICANCE: Eccentric exercise accompanied by caloric restriction attenuates HFD-related NAFLD by promoting M2 macrophages phenotype and inhibiting M1 macrophages in liver. These findings may be help to designing better non-pharmacological intervention programs for NAFLD patients.


Assuntos
Restrição Calórica/métodos , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Macrófagos/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Fígado/patologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/terapia , Condicionamento Físico Animal/métodos
6.
Rev Assoc Med Bras (1992) ; 66(2): 222-226, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32428159

RESUMO

OBJECTIVE: To verify the relationship of intermittent fasting in the bodyweight of overweight and obese individuals through a systematic literature review. METHODS: This is a systematic review based on randomized controlled trials. The articles were consulted in the databases: Science Direct, PubMed e BVS. This review was evaluated through the PRISMA recommendation. RESULTS: After the selection process, four articles were included in this review, comparing intermittent fasting (IF) with calorie restriction diet (CRD) as a control group. In 2 studies using similar protocols, there was no significant reduction in body weight of overweight or obese subjects. In the other two studies using different protocols, weight loss was significant in the IF group compared to the CRD group. CONCLUSIONS: Results did not provide evidence of the effect of intermittent fasting on weight loss in overweight or obese individuals.


Assuntos
Peso Corporal/fisiologia , Jejum/fisiologia , Obesidade/dietoterapia , Sobrepeso/dietoterapia , Perda de Peso/fisiologia , Restrição Calórica/métodos , Dieta Redutora/métodos , Humanos , Obesidade/metabolismo , Sobrepeso/metabolismo , Resultado do Tratamento
7.
Medicine (Baltimore) ; 99(17): e19769, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332617

RESUMO

INTRODUCTION: High blood pressure is the leading modifiable risk factor for cardiovascular disease, and is associated with high morbidity and mortality and with significant health care costs for individuals and society. However, fewer than half of the patients with hypertension receiving pharmacological treatment have adequate blood pressure control. The main reasons for this are therapeutic inertia, lack of adherence to treatment, and unhealthy lifestyle (i.e., excess dietary fat and salt, sedentary lifestyle, and overweight). Cardiovascular risk and mortality are greater in hypertensive patients who are receiving treatment but have suboptimal control of blood pressure. METHODS/DESIGN: This is a multicentre, parallel, 2-arm, single-blind (outcome assessor), controled, cluster-randomized clinical trial. General practitioners and nurses will be randomly allocated to the intervention group (self-management of antihypertensive medication, self-measurement of blood pressure, hypocaloric and low sodium diet, and physical exercise) or the control group (regular clinical practice). A total of 424 patients in primary care centers who use 2 or more antihypertensive drugs and blood pressure of at least 130/80 during 24-hambulatory blood pressure monitoring will be recruited. The primary outcome is systolic blood pressure at 12 months. The secondary outcomes are blood pressure control (<140/90 mm Hg); quality of life (EuroQol 5D); direct health care costs; adherence to use of antihypertensive medication; and cardiovascular risk (REGICOR and SCORE scales). DISCUSSION: This trial will be conducted in the primary care setting and will evaluate the impact of a multifactorial intervention consisting of self-management of blood pressure, antihypertensive medications, and lifestyle modifications (hypocaloric and low sodium diet and physical exercise).


Assuntos
Anti-Hipertensivos/normas , Determinação da Pressão Arterial/normas , Hipertensão/tratamento farmacológico , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Determinação da Pressão Arterial/métodos , Restrição Calórica/métodos , Análise por Conglomerados , Dieta Hipossódica/métodos , Exercício Físico/fisiologia , Feminino , Humanos , Hipertensão/psicologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Autogestão/métodos , Autogestão/psicologia , Cooperação e Adesão ao Tratamento/psicologia , Resultado do Tratamento
8.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32073608

RESUMO

BACKGROUND: The question of whether there is daytime time variation in diet-induced thermogenesis (DIT) has not been clearly answered. Moreover, it is unclear whether a potential diurnal variation in DIT is preserved during hypocaloric nutrition. OBJECTIVE: We hypothesized that DIT varies depending on the time of day and explored whether this physiological regulation is preserved after low-calorie compared with high-calorie intake. DESIGN: Under blinded conditions, 16 normal-weight men twice underwent a 3-day in-laboratory, randomized, crossover study. Volunteers consumed a predetermined low-calorie breakfast (11% of individual daily kilocalorie requirement) and high-calorie dinner (69%) in one condition and vice versa in the other. DIT was measured by indirect calorimetry, parameters of glucose metabolism were determined, and hunger and appetite for sweets were rated on a scale. RESULTS: Identical calorie consumption led to a 2.5-times higher DIT increase in the morning than in the evening after high-calorie and low-calorie meals (P < .001). The food-induced increase of blood glucose and insulin concentrations was diminished after breakfast compared with dinner (P < .001). Low-calorie breakfast increased feelings of hunger (P < .001), specifically appetite for sweets (P = .007), in the course of the day. CONCLUSIONS: DIT is clearly higher in the morning than in the evening, irrespective of the consumed calorie amount; that is, this physiological rhythmicity is preserved during hypocaloric nutrition. Extensive breakfasting should therefore be preferred over large dinner meals to prevent obesity and high blood glucose peaks even under conditions of a hypocaloric diet.


Assuntos
Restrição Calórica/efeitos adversos , Dieta/efeitos adversos , Refeições/fisiologia , Período Pós-Prandial/fisiologia , Termogênese/fisiologia , Adulto , Apetite/fisiologia , Glicemia/metabolismo , Desjejum/fisiologia , Restrição Calórica/métodos , Calorimetria Indireta , Estudos Cross-Over , Dieta/métodos , Método Duplo-Cego , Ingestão de Energia , Metabolismo Energético , Humanos , Insulina/sangue , Masculino , Fatores de Tempo
9.
FASEB J ; 34(1): 1846-1858, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914635

RESUMO

P53 has been implicated in the pathogenesis of obesity and diabetes; however, the mechanisms and tissue sites of action are incompletely defined. Therefore, we investigated the role of hepatocyte p53 in metabolic homeostasis using a hepatocyte-specific p53 knockout mouse model. To gain further mechanistic insight, we studied mice under two complementary conditions of restricted weight gain: vertical sleeve gastrectomy (VSG) or food restriction. VSG or sham surgery was performed in high-fat diet-fed male hepatocyte-specific p53 wild-type and knockout littermates. Sham-operated mice were fed ad libitum or food restricted to match their body weight to VSG-operated mice. Hepatocyte-specific p53 ablation in sham-operated ad libitum-fed mice impaired glucose homeostasis, increased body weight, and decreased energy expenditure without changing food intake. The metabolic deficits induced by hepatocyte-specific p53 ablation were corrected, in part by food restriction, and completely by VSG. Unlike food restriction, VSG corrected the effect of hepatocyte p53 ablation to lower energy expenditure, resulting in a greater improvement in glucose homeostasis compared with food restricted mice. These data reveal an important new role for hepatocyte p53 in the regulation of energy expenditure and body weight and suggest that VSG can improve alterations in energetics associated with p53 dysregulation.


Assuntos
Hepatócitos/metabolismo , Doenças Metabólicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/fisiologia , Restrição Calórica/métodos , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Alimentos , Gastrectomia/métodos , Homeostase/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Ganho de Peso/fisiologia , Perda de Peso
10.
Nutrients ; 12(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906264

RESUMO

: Colorectal cancer has the second highest cancer-related mortality rate, with an estimated 881,000 deaths worldwide in 2018. The urgent need to reduce the incidence and mortality rate requires innovative strategies to improve prevention, early diagnosis, prognostic biomarkers, and treatment effectiveness. Caloric restriction (CR) is known as the most robust nutritional intervention that extends lifespan and delays the progression of age-related diseases, with remarkable results for cancer protection. Other forms of energy restriction, such as periodic fasting, intermittent fasting, or fasting-mimicking diets, with or without reduction of total calorie intake, recapitulate the effects of chronic CR and confer a wide range of beneficial effects towards health and survival, including anti-cancer properties. In this review, the known molecular, cellular, and organismal effects of energy restriction in oncology will be discussed. Energy-restriction-based strategies implemented in colorectal models and clinical trials will be also revised. While energy restriction constitutes a promising intervention for the prevention and treatment of several malignant neoplasms, further investigations are essential to dissect the interplay between fundamental aspects of energy intake, such as feeding patterns, fasting length, or diet composition, with all of them influencing health and disease or cancer effects. Currently, effectiveness, safety, and practicability of different forms of fasting to fight cancer, particularly colorectal cancer, should still be contemplated with caution.


Assuntos
Restrição Calórica/métodos , Neoplasias Colorretais/prevenção & controle , Dieta/métodos , Neoplasias Colorretais/mortalidade , Ingestão de Energia , Jejum , Humanos
11.
J Phys Act Health ; 17(2): 204-210, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31899888

RESUMO

BACKGROUND: The benefits of weight loss programs on mood, cognitive, and motor behavior are largely limited to those of calorie restriction or exercise alone. Our aim was to investigate the effect of combined calorie restriction and aerobic exercise intervention on mood, brain activity, and cognitive and motor behavior in overweight and obese women. METHODS: Participants aged 36-56 years were randomized to either a control or an experimental group (aerobic exercise + 12.5% energy intake reduction) for a 6-month period. Changes in brain-derived neurotrophic factor levels, mood, prefrontal cortex activity, cognitive and motor performance were assessed. RESULTS: Confusion and depression increased in the control group (P < .05), whereas tension decreased in the experimental group (P < .05). Brain-derived neurotrophic factor level and learning of a speed-accuracy task remained unchanged. Although prefrontal cortex activity and executive functions were not affected, the reaction time of visual scanning and associative learning were improved in the experimental group (P < .05). An improvement in reaction time during the speed-accuracy task was observed (P < .05). CONCLUSION: Combined calorie restriction and aerobic exercise intervention improved the psychosocial state, had little impact on cognition, and no effect on brain activity and learning of the speed-accuracy task.


Assuntos
Afeto/fisiologia , Restrição Calórica/métodos , Cognição/fisiologia , Exercício Físico/fisiologia , Atividade Motora/fisiologia , Obesidade/terapia , Sobrepeso/terapia , Adulto , Feminino , Humanos , Estudos Prospectivos
12.
Obes Surg ; 30(1): 119-126, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31529393

RESUMO

BACKGROUND: Fatty liver in obese patients increases the technical difficulty of bariatric surgery. Pre-operative weight loss with a very-low-calorie diet (VLCD) is commonly used to facilitate surgery. Few studies have quantified the systemic effect of rapid pre-operative weight loss on body composition. The objective of this study is to evaluate body composition changes in bariatric surgery patients undergoing a VLCD. METHODS: Body composition assessments were performed between August 2017 and January 2019 using dual-energy X-ray absorptiometry immediately before and after a 2-week VLCD at St Vincent's Hospital Melbourne. Data collected prospectively pre- and post-VLCD included total body weight, excess body weight, body mass index (BMI), lean body mass (LBM), fat mass (FM) and bone mineral content (BMC). The pre- and post-operative results were compared. RESULTS: Forty-four patients completed both the 2-week VLCD and body composition assessments. Following a 2-week VLCD, patients lost a mean of 4.5 kg (range - 0.3 to 9.5) in a total body weight and 8.8% (range - 0.9 to 17.1) of excess body weight, with a mean reduction in body mass index of 1.6 kg/m2 (range - 0.2 to 3.1). Loss of LBM was 2.8 kg and was significantly greater than loss of FM, 1.7 kg (p < 0.05). BMC changes were insignificant. CONCLUSION: A VLCD is an effective tool for pre-operative weight reduction. In this cohort, a large amount of the total weight loss was attributed to a loss of lean body mass. The impact of significant lean body mass loss and its relationship to short- and long-term health outcomes warrants further assessment.


Assuntos
Cirurgia Bariátrica , Composição Corporal/fisiologia , Restrição Calórica , Dieta Redutora , Obesidade Mórbida/dietoterapia , Obesidade Mórbida/cirurgia , Cuidados Pré-Operatórios/métodos , Absorciometria de Fóton , Adulto , Índice de Massa Corporal , Restrição Calórica/métodos , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/metabolismo , Perda de Peso/fisiologia , Adulto Jovem
13.
J Gerontol A Biol Sci Med Sci ; 75(1): 4-13, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30854544

RESUMO

Since the initial suggestion that rapamycin, an inhibitor of target of rapamycin (TOR) nutrient signaling, increased lifespan comparable to dietary restriction, investigators have viewed rapamycin as a potential dietary restriction mimetic. Both dietary restriction and rapamycin increase lifespan across a wide range of evolutionarily diverse species (including yeast, Caenorhabditis elegans, Drosophila, and mice) as well as reducing pathology and improving physiological functions that decline with age in mice. The purpose of this article is to review the research comparing the effect of dietary restriction and rapamycin in mice. The current data show that dietary restriction and rapamycin have different effects on many pathways and molecular processes. In addition, these interventions affect the lifespan of many genetically manipulated mouse models differently. In other words, while dietary restriction and rapamycin may have similar effects on some pathways and processes; overall, they affect many pathways/processes quite differently. Therefore, rapamycin is likely not a true dietary restriction mimetic. Rather dietary restriction and rapamycin appear to be increasing lifespan and retarding aging largely through different mechanisms/pathways, suggesting that a combination of dietary restriction and rapamycin will have a greater effect on lifespan than either manipulation alone.


Assuntos
Envelhecimento/fisiologia , Restrição Calórica/métodos , Longevidade/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Animais , Humanos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
14.
J Gerontol A Biol Sci Med Sci ; 75(1): 24-31, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30891588

RESUMO

Branched-chain amino acids (BCAAs) have been suggested to be particularly potent activators of Target of Rapamycin (TOR) signaling. Moreover, increased circulating BCAAs are associated with higher risk of insulin resistance and diabetes in both mice and humans, and with increased mortality in mice. However, it remains unknown if BCAAs play a more prominent role in longevity than do other essential amino acids (EAAs). To test for a more prominent role of BCAAs in lifespan and related traits in Drosophila, we restricted either BCAAs or a control group of three other EAAs, threonine, histidine and lysine (THK). BCAA restriction induced compensatory feeding, lipid accumulation, stress resistance and amelioration of age-related gut pathology. It also extended lifespan in a dietary-nitrogen-dependent manner. Importantly, the control restriction of THK had similar effects on these phenotypes. Our control diet was designed to have every EAA equally limiting for growth and reproduction, and our findings therefore suggest that the level of the most limiting EAAs in the diet, rather than the specific EAAs that are limiting, determines the response of these phenotypes to EAA restriction.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Aminoácidos Essenciais/metabolismo , Restrição Calórica/métodos , Diabetes Mellitus Experimental/metabolismo , Resistência à Insulina/fisiologia , Longevidade/fisiologia , Animais , Western Blotting , Drosophila , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Fenótipo , Transdução de Sinais
15.
Chin J Integr Med ; 26(1): 62-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30328570

RESUMO

Traditional glucose-lowering chemical agents, including various types of insulin and insulin secretagogues, insulin sensitizers, gliptins, etc., are based on diabetic pathogenesis of insulin resistance (IR) and islet insufficiency. Numerous evidence-based medical studies have shown that these traditional hypoglycemic chemical agents do not provide cardiovascular benefit to patients with type 2 diabetes mellitus (T2DM) and may even increase the risk of all-cause mortality. Based on research evidence published to date, these studies show that overload of energy could increase the incidence and prevalence of T2DM, and reduction in the heat load can significantly reduce the incidence of T2DM. Therefore, the essence of T2DM is heat overload, meaning heat overload is the etiology of obese T2DM. At the same time, results of numerous studies show that heat overloading is the cause of IR. IR and islet dysfunction are protective factors in intervening with heat overload. These drugs, which are based on the mechanisms of IR and islet insufficiency, increase caloric reserve and cause or worsen obesity, which is equivalent to exacerbating the basic etiology and the cardiovascular risk factor of T2DM. Thus, a reasonable strategy for prevention and treatment of obese T2DM appears to promote the negative balance of calories and the elimination of caloric reserves. Chinese herbal medicines can promote negative balance of heat in many aspects, which can bring new hope for prevention and treatment of T2DM.


Assuntos
Restrição Calórica/métodos , Diabetes Mellitus Tipo 2/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Hipoglicemiantes/uso terapêutico , Obesidade/terapia , Humanos
16.
Autophagy ; 16(1): 188-189, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31690168

RESUMO

The age-related decline in organismal fitness results in vulnerability to pathologies and eventual lethal decay. One way to counteract cellular aging and to delay and/or prevent the onset of age-related maladies is the reduction of calorie intake or the institution of fasting regimens. Caloric restriction mimetics (CRMs) have the ability to imitate the health-promoting and lifespan-extending effects of caloric restriction without the need for dietary restriction. CRMs induce an increase in autophagic flux in response to the deacetylation of cellular proteins in the absence of cytotoxicity. Here we report the development of a high-throughput discovery platform for novel CRMs that uses systems biology approaches, in vitro validation and functional tests employing in vivo disease models. This workflow led to the identification of 3,4-dimethoxychalcone (3,4-DC) as a novel CRM that stimulated TFEB (transcription factor EB)- and TFE3 (transcription factor E3)-dependent macroautophagy/autophagy. 3,4-DC showed cardioprotective effects and stimulated anticancer immunosurveillance in the context of immunogenic chemotherapy.


Assuntos
Acetilcoenzima A/metabolismo , Autofagia/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Fatores de Transcrição/metabolismo , Animais , Autofagia/fisiologia , Restrição Calórica/métodos , Senescência Celular/fisiologia , Humanos
17.
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
18.
Appl Physiol Nutr Metab ; 45(3): 340-343, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31751150

RESUMO

This study compared the weight loss efficacy of alternate-day fasting (ADF) versus daily calorie restriction (CR) in adults with subclinical hypothyroidism. After 6 months, body weight decreased (P < 0.001) similarly by ADF (-7% ± 1%) and CR (-8% ± 2%). Insulin resistance decreased (P < 0.05) more by ADF versus CR. Free thyroxin and thyroid-stimulating hormone remained unchanged. Thus, ADF and CR produce similar weight loss in this population, without affecting thyroid hormone levels. Novelty Intermittent fasting and daily restriction produce similar reductions in body weight in subjects with subclinical hypothyroidism.


Assuntos
Restrição Calórica/métodos , Jejum/fisiologia , Hipotireoidismo/complicações , Obesidade/complicações , Obesidade/dietoterapia , Perda de Peso/fisiologia , Adolescente , Adulto , Idoso , Dieta Redutora/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Br J Nutr ; 123(5): 553-563, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-31813388

RESUMO

We assessed the effects of increased Ca consumption from fat-free milk in an energy-restricted diet and educational activities in the metabolic control of overweight type 2 diabetes mellitus (T2DM) patients. Fourteen subjects with T2DM (BMI 29·4 (sd 4·5) kg/m2, low habitual Ca consumption (<600 mg/d)) were included in this randomised, crossover clinical trial. Subjects were randomly allocated to one of the two interventions: drink containing 700 mg of Ca (DAIR) or drink containing 0 mg of Ca (CONT) for ninety consecutive days each. Energy-restricted diets (-500 kcal/d; -2092 kJ/d), containing 800 mg of Ca from dietary sources/d, were prescribed for both groups. Questionnaires were applied at baseline and at the end of the study to assess the subjects' knowledge on the disease and on self-care, biochemical variables and physical activity. Blood pressure, food intake, body composition and anthropometry were assessed at baseline, days 45 and 90. There was a higher reduction of body fat %, waist circumference, hip circumference, neck circumference, waist:hip ratio, sagittal abdominal diameter, diastolic/systolic blood pressure and an increase in fat-free mass % in DAIR than in CONT. Uric acid, fasting glucose, Hb1Ac, parathyroid hormone and alanine aminotransferase concentrations reduced and vitamin D concentration increased after 90 d in DAIR compared with CONT. The consumption of energy-restricted diet containing 1200 mg Ca/d seems to favour metabolic control in subjects with T2DM. The educational activities increased the knowledge on the disease care.


Assuntos
Cálcio na Dieta/administração & dosagem , Restrição Calórica/métodos , Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos/métodos , Sobrepeso/dietoterapia , Educação de Pacientes como Assunto/métodos , Adulto , Animais , Glicemia/análise , Composição Corporal , Peso Corporal , Estudos Cross-Over , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Leite/química , Sobrepeso/complicações , Sobrepeso/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Autocuidado/métodos , Autocuidado/psicologia , Resultado do Tratamento , Circunferência da Cintura , Relação Cintura-Quadril
20.
Biochim Biophys Acta Mol Basis Dis ; 1866(3): 165612, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816437

RESUMO

Aging is the main risk factor for chronic diseases and disablement in human societies with a great impact in social and health care expenditures. So far, aging and, eventually, death are unavoidable. Nevertheless, research efforts on aging-associated diseases with the aim not only to extend life span but also to increment health span in an attempt to delay, stop and even reverse the aging process have not stopped growing. Caloric restriction extends both health and life span in several short-lived experimental models and has brought to light the role of different molecular effectors involved in nutrient sensing pathways and longevity. This opens the possibility of modulating these molecular effectors also in humans to increase longevity and health span. The difficulty to implement caloric restricted diets in humans has led to the development of new bearable diets such as time-restricted feeding, intermittent fasting or diets with limited amounts of some nutrients and to the search of pharmacological agents, targeted to the effectors that mediate the extension of life and health span in response to these anti-aging diets. Pharmacological approaches that eliminate senescent cells or prevent primary causes of aging such as telomere attrition also emerge as potential anti-aging strategies. In the present article, we review these possible nutritional and pharmacological interventions designed to mitigate and/or delay the aging process and to increase health and life span.


Assuntos
Envelhecimento/fisiologia , Animais , Restrição Calórica/métodos , Doença Crônica , Dieta/métodos , Jejum/fisiologia , Humanos , Longevidade/fisiologia
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