Ayuno intermitente y restricción calórica como tratamiento coadyuvante en enfermedad de Alzheimer y esclerosis múltiple / Intermittent Fasting and Caloric Restriction as an Adjunctive Treatment in Alzheimer's Disease and Multiple Sclerosis

Las enfermedades de Alzheimer y esclerosis múltiple son neurodegenerativas, con tratamientos complejos y de costos elevados, orientados a disminuir la progresión de la sintomatología. Sin embargo, a causa de la falta de terapias adecuadas y de los posibles efectos adversos ocasionados por tratamientos de primera línea, es necesario implementar mejores abordajes terapéuticos complementarios que no produzcan mayores efectos secundarios y mejoren la sintomatología de dichas patologías. La restricción calórica y el ayuno intermitente han demostrado ser estrategias novedosas y beneficiosas en enfermedades neurodegenerativas, a través de mecanismos inmunitarios, metabólicos y fisiológicos. Con el objetivo de determinar el uso del ayuno intermitente y la restricción calórica como tratamiento coadyuvante en esclerosis múltiple y enfermedad de Alzheimer, se realizó una revisión narrativa de artículos originales en revistas científicas, en idiomas inglés y español, de 2018 a 2022. El uso de la restricción calórica y ayuno intermitente han generado cambios positivos produciendo disminución de estados proinflamatorios, estrés oxidativo y envejecimiento. Se consideran abordajes que modulan la progresión de la enfermedad y mejoran la función cognitiva por vías de señalización de monofosfato de adenosina cinasa, factor de crecimiento similar a la insulina y la enzima sirtuina, generando un efecto neuroprotector.

Alzheimer's disease and multiple sclerosis are neurodegenerative disorders with expensive and complex treatments aimed at reducing the progression of symptoms. However, due to the lack of adequate therapies and the possible adverse effects caused by first-line treatments, it's necessary to implement better complementary therapeutic approaches that do not produce major side effects and improve symptoms. Caloric restriction and intermittent fasting have been shown to be novel and beneficial strategies in neurodegenerative diseases, through immune, metabolic, and physiological mechanisms. To determine the use of intermittent fasting and caloric restriction as a new treatment in multiple sclerosis and Alzheimer's disease, a narrative review of original articles in both national and international scientific journals, in English and Spanish languages with no greater obsolescence than five years. The use of caloric restriction and intermittent fasting have generated positive changes, producing a decrease in pro-inflammatory states, oxidative stress, and aging. Approaches that modulate disease progression and improve cognitive function of adenosine monophosphate kinase, insulin-like growth factor, and sirtuin enzyme pathways are considered, generating a neuroprotective effect.

Dieta rica em fibra promove efeitos metabólicos, hormonais e de saciedade em mulheres obesas com restrição calórica de curto prazo / High-fiber diet promotes metabolic, hormonal, and satiety effects in obese women on a short-term caloric restriction

ABSTRACT Background: Several mechanisms, including excessive hunger, account for patients' difficulties in maintaining weight loss and dietary changes after caloric restriction. Objective: To evaluate the effect of short-term high-fiber calorie-restricted diet in appetite-regulating hormones, and hunger and satiety sensations in women with obesity. Methds: In a randomized controlled trial study, thirty women with body mass index (BMI) higher than 30 kg/m2, and aged from 20 to 50 years were hospitalized following a calorie-restricted diet (1000 kcal/day) for three days. The experimental group (n=15) received high-fiber diet and the control group (n=15), conventional diet. Body weight, BMI, resting energy expenditure (REE), acylated and total ghrelin, leptin, insulin and glucose, and hunger and satiety sensations were evaluated. Linear regression models with mixed effects (fixed and random effects) helped to assess the variables between the two groups and within the groups. Results: Body weight and BMI decreased in both the experimental and control groups (P<0.001). After the high-fiber diet, postprandial acylated ghrelin (P=0.04), glucose (P<0.001), insulin (P=0.04), and leptin (P=0.03) levels as well as the HOMA-IR index (P=0.01) decreased, whereas satiety improved (P=0.02). Obese women that followed the conventional diet had increased body fat percentage (P=0.04) and lower REE (P=0.02). The two diets did not differ in terms of hunger sensation. Conclusion: A short-term high-fiber diet improves satiety sensations and metabolic parameters while suppressing postprandial acylated ghrelin (60 minutes) and maintaining the resting energy expenditure.

RESUMO Contexto: Vários mecanismos, incluindo a fome excessiva, são responsáveis pelas dificuldades dos pacientes em manter a perda de peso e mudanças na dieta após a restrição calórica. Objetivo: Avaliar o efeito da dieta de curta duração rica em fibras e com restrição calórica nos hormônios reguladores do apetite e nas sensações de fome e saciedade em mulheres com obesidade. Métodos: Em um estudo randomizado controlado, 30 mulheres com índice de massa corporal (IMC) superior a 30 kg/m2 e com idade entre 20 e 50 anos foram hospitalizadas seguindo dieta com restrição calórica (1000 kcal/dia) por 3 dias. O grupo experimental (n=15) recebeu dieta rica em fibras e o grupo controle (n=15), dieta convencional. Foram avaliados peso corporal, IMC, gasto energético de repouso (GER), grelina acilada e total, leptina, insulina e glicose e sensações de fome e saciedade. Modelos de regressão linear com efeitos mistos (efeitos fixos e aleatórios) ajudaram a avaliar as variáveis entre os dois grupos e dentro dos grupos. Resultados: O peso corporal e o IMC diminuíram tanto no grupo experimental quanto no controle (P<0,001). Após a dieta rica em fibras, os níveis de grelina acilada pós-prandial (P=0,04), glicose (P<0,001), insulina (P=0,04) e leptina (P=0,03), bem como o índice HOMA-IR (P=0,01) diminuiu, enquanto a saciedade melhorou (P=0,02). Mulheres obesas que seguiram a dieta convencional apresentaram aumento do percentual de gordura corporal (P=0,04) e menor GER (P=0,02). As duas dietas não diferiram em termos de sensação de fome. Conclusão: Uma dieta rica em fibras de curto prazo melhora as sensações de saciedade e os parâmetros metabólicos, suprimindo a grelina acilada pós-prandial (60 minutos) e mantendo o gasto energético de repouso.

Effect of caloric restriction on myocardial ischemia/reperfusion injury in mice and its mechanism / 中国生物制品学杂志

@#Objective To investigate the effect of caloric restriction(CR)on myocardial ischemia/reperfusion injury(MI/RI)in mice and its mechanism.Methods C57 mice were randomly divided into normal diet group(AL group,free feeding)and CR group(diet decreased by 10% every 2 weeks)for 8 weeks and monitored for weight changes.Each group was divided into sham operation group and MI/RI group,total 4 groups,AL + Sham group,AL + I/R group,CR + Sham group and CR + I/R group).The left anterior descending coronary artery was ligated for 30 minutes and then reperfused for 24 hours in mice of MI/RI group and mice in Sham group were only threaded but not ligated.The mice were determined for myocardial ischemia and infarct size by Evans blue/TTC staining,observed for the pathology of myocardium by HE staining,determined for the activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD)and the contents of creatine kinase-MB(CK-MB)and malondialdehvde(MDA)in myocardium by the corresponding kits,determined for serum levels of IL-1β and IL-18 by ELISA and detected for the expression of pyroptosis-associated proteins in myocardium by Western blot.Results After 8weeks,the weights of mice in CR group[(24.54 ± 0.41)g]were significantly lower than those in AL group[(31.46 ±0.25)g](t = 14.34,P<0.05).Compared with those in AL + I/R group,the area of myocardial ischemia in CR + I/R group showed no significant difference(t = 0.783 0,P>0.05),while the area of myocardial infarction decreased significantly(t = 7.250,P<0.01);The myocardial arrangement was relatively neat,and the degree of pathological changes was obviously reduced;LDH activity,CK-MB and MDA contents decreased significantly(t = 4.331,2.875 and 5.343 respectively,each P<0.05),while SOD activity increased significantly(t = 4.211,P<0.05);Serum levels of IL-1β and IL-18 decreased significantly(t = 3.375 and 4.266 respectively,each P<0.05);The expression levels of nod-like receptor protein 3(NLRP3),gasdermin D(GSDMD),apoptosis-associated speckle-like protein(ASC)and caspase-1 significantly decreased(t = 3.412,3.420,3.480 and 2.585 respectively,each P<0.05).Conclusion CR alleviated MI/RI in mice,and its mechanism was related to the inhibition of cardiac pyroptosis.

Effect of Hypoenergetic Diet Combined With Pumpkin Seed Flour Consumption on Obese Women

Abstract Background Dietary treatment containing fiber-rich foods may contribute to lowering weight in obese women. Objective To investigate the effect of a hypoenergetic diet combined with pumpkin seed flour (PSF) consumption on diet quality, anthropometric indices, and glucose and lipid metabolism in obese women. Methods We conducted a randomized, double-blind, placebo-controlled, 90-day clinical trial with obese women, distributed into the following two groups: hypoenergetic diet + placebo (PG) and hypoenergetic diet + pumpkin seed flour (PSFG). A total of 100 participants were included in the PSFG (n = 47) and PG (n = 53). We evaluated neck circumference (NC); waist to height ratio; conicity index; fat mass (FM); lipid profile; blood concentrations of glucose and insulin; homeostatic model assessment for insulin resistance (HOMA-IR); quantitative insulin sensitivity check index (QUICKI); and blood pressure at baseline, 30, 60, and 90 days. Dietary analysis was determined by differences between diet quality indices before and after prescribing the experimental diet. Chi-squared, Student's t-tests and analysis for repeated measures were used, and values were considered significant at p < 0.05. Results The dietary pattern improved after 90 days in both groups. The PSFG presented lower NC (p < 0.001), FM (p = 0.010), triglycerides (TG) (p = 0.025), insulin (p = 0.003), and HOMA-IR (p = 0.018). The PG presented a lower diastolic blood pressure (p = 0.004) and low-density lipoprotein cholesterol (LDL-c) (p = 0.056). Conclusion A hypoenergetic diet combined with PSF consumption contributes to lowering NC, FM, HOMA-IR, TG, and insulin concentrations.

Efeito da dieta hipocalórica na pressão arterial e demais cofatores da síndrome metabólica / Effect of hypocaloric diet on blood pressure and other cofactors of metabolic syndrome

Introdução: a hipertensão arterial sistêmica (HAS) está associada a fatores de risco metabólicos e pode ser definida como uma doença crônica multifatorial, com valores persistentes de pressão arterial sistólica (PAS) e (ou) pressão arterial diastólica (PAD) maiores ou iguais a 140 mmHg x 90 mmHg, respectivamente. A HAS é um dos fatores que compõem a síndrome metabólica (SM) juntamente com a hiperglicemia, dislipidemia e (ou) obesidade central. Modificações no estilo de vida, como a alimentação e perda de peso, demonstraram melhorar os parâmetros cardiometabólicos nos pacientes com HAS e SM. Objetivo: verificar o efeito de uma dieta hipocalórica na antropometria, na pressão arterial e em outros cofatores da síndrome metabólica. Metodologia: trata-se de um ensaio clínico não randomizado, retrospectivo, com dados secundários, em que o mesmo grupo foi de "intervenção" e "comparador", e cujos dados foram coletados antes (baseline) e após a intervenção. A pesquisa foi realizada com 84 pacientes, adultos, com síndrome metabólica, de ambos os sexos. Os pacientes seguiram dieta com restrição calórica de 200 a 500kcal/dia, com cálculo energético em torno de 20kcal/kg de peso, valor energético total não inferior a 1200kcal, durante um período de dois meses. Foi utilizada estatística descritiva e o teste t pareado ou Wilcoxon-Sign-Rank intragrupo para analisar as variações ao longo do tempo (p < 0,05). Resultado:houve uma redução na antropometria (índice de massa corporal, circunferência da cintura, circunferência do braço e circunferência do quadril), PAS e PAD, glicemia de jejum e triglicerídeos com p< 0,05 dos pacientes após a intervenção, mas não houve melhora no HDL (p > 0,05). Conclusão: a dieta hipocalórica reduziu as medidas antropométricas, a pressão arterial e os demais cofatores da SM nos pacientes avaliados após o acompanhamento de dois meses.

Introduction: systemic arterial hypertension (SAH) is associated with metabolic risk factors and can be defined as a multifactorial chronic disease, with persistent values of systolic blood pressure (SBP) and (or) diastolic blood pressure (DBP) greater than or equal to 140 mmHg x 90 mmHg, respectively. SAH is one of the factors that make up the metabolic syndrome (MS) along with hyperglycemia, dyslipidemia and (or) central obesity. Lifestyle modifications, such as diet and weight loss, have been shown to improve cardiometabolic parameters in patients with SAH and MS. Objective: to verify the effect of a hypocaloric diet on anthropometry, blood pressure and other cofactors of the metabolic syndrome. Methodology: this is a non-randomized, retrospective clinical trial, with secondary data, in which the same group was "intervention" and "comparator", and whose data were collected before (baseline) and after the intervention. Research was carried out with 84 patients, adults, with metabolic syndrome, of both sexes. Patients followed a calorie-restricted diet of 200 to 500kcal/day, with energy calculation around 20kcal/kg of weight, total energy value not less than 1200kcal, during a period of two months. Descriptive statistics and the paired t test or intragroup Wilcoxon-Sign-Rank were used to analyze variations over time (p < 0.05). Result: there was a reduction in anthropometry (body mass index, waist circumference, arm circumference and hip circumference), SBP and DBP, fasting glucose and triglycerides with p<0.05 of patients after the intervention, but there was no improvement in HDL (p > 0.05). Conclusion: the hypocaloric diet reduced anthropometric measurements, blood pressure and other MS cofactors in the patients evaluated after a two-month follow-up.

Body Recomposition: would it be possible to induce fat loss and muscle hypertrophy at the same time? / Recomposição Corporal: seria possível induzir emagrecimento e hipertrofia muscular ao mesmo tempo?

abstract Adipose tissue reduction and lean mass increase are frequent goals in exercise programs aimed at health and aesthetics. In this context, when postulating the need for an energy deficit for weight loss and a caloric surplus for muscle hypertrophy, was developed the idea that it would not be possible for both phenomena to exist simultaneously. Contrarily, the term "Body Recomposition" (BR) emerges in the literature, a phenomenon in which weight loss and muscle hypertrophy occur at the same time. BR has already been observed using different techniques for analyzing body composition, from doubly indirect methods to magnetic resonance imaging, and in different population groups, namely: adolescents, sedentary or physically active adults, the elderly and people with excess weight, as well as practitioners of sports, including bodybuilding. BR occurs with precise nutritional adjustment, with protein consumption above the recommended daily intake (0.8 g/kg), in ranges between 2.4 and 3.4 g/kg of body mass/day. Different types of exercises can lead to BR, from strength training, through high-intensity circuit training, high-intensity interval training, and even concurrent training - most often with a high weekly frequency.

resumo Redução de tecido adiposo e aumento de massa magra se constituem como objetivos frequentes em programas de exercícios voltados à saúde e à estética. Nesse contexto, ao se postular a necessidade de déficit energético para o emagrecimento e superavit calórico para a hipertrofia muscular, desenvolveu-se a ideia de que não seria possível a existência de ambos os fenômenos de forma simultânea. Contrariamente, emerge na literatura o termo "Recomposição Corporal" (RC), fenômeno no qual ocorre emagrecimento e hipertrofia muscular ao mesmo tempo. A RC já foi observada com emprego de diferentes técnicas de análise da composição corporal, desde métodos duplamente indiretos até ressonância nuclear magnética, e em diversos grupos populacionais, a saber: adolescentes, adultos sedentários ou fisicamente ativos, idosos e pessoas com excesso de peso, além de praticantes de modalidades esportivas, inclusive fisiculturismo. A RC ocorre com ajuste nutricional preciso, com consumo de proteínas acima da ingestão diária recomendada (0,8 g/kg), em faixas entre 2,4 e 3,4 g/kg de massa corporal/dia. Diferentes tipos de exercícios físicos podem conduzir à RC, desde o treinamento de força, passando pelo treinamento em circuito em alta intensidade, treinamento intervalado de alta intensidade e, inclusive, treinamento concorrente - na maioria das vezes com elevada frequência semanal.

Restricted feeding modulates peripheral clocks and nutrient sensing pathways in rats

ABSTRACT Objective: Feeding restriction in rats alters the oscillators in suprachiasmatic, paraventricular, and arcuate nuclei, hypothalamic areas involved in food intake. In the present study, using the same animals and experimental protocol, we aimed to analyze if food restriction could reset clock genes ( Clock, Bmal1 ) and genes involved in lipid metabolism ( Pgc1a, Pparg, Ucp2 ) through nutrient-sensing pathways ( Sirt1, Ampk, Nampt ) in peripheral tissues. Materials and methods: Rats were grouped according to food access: Control group (CG, food ad libitum ), Restricted night-fed (RF-n, food access during 2 h at night), Restricted day-fed (RF-d, food access during 2 h in the daytime), and Day-fed (DF, food access during 12 h in the daytime). After 21 days, rats were decapitated at ZT3 (0900-1000 h), ZT11 (1700-1800 h), or ZT17 (2300-2400 h). Blood, liver, brown (BAT) and peri-epididymal (PAT) adipose tissues were collected. Plasma corticosterone and gene expression were evaluated by radioimmunoassay and qPCR, respectively. Results: In the liver, the expression pattern of Clock and Bmal1 shifted when food access was dissociated from rat nocturnal activity; this phenomenon was attenuated in adipose tissues. Daytime feeding also inverted the profile of energy-sensing and lipid metabolism-related genes in the liver, whereas calorie restriction induced a pre-feeding increased expression of these genes. In adipose tissues, Sirt1 expression was modified by daytime feeding and calorie restriction, with concomitant expression of Pgc1a , Pparg , and Ucp2 but not Ampk and Nampt . Conclusion: Feeding restriction reset clock genes and genes involved in lipid metabolism through nutrient-sensing-related genes in rat liver, brown, and peri-epididymal adipose tissues.

Feed restriction since lactation has reduced anxiety in adult Wistar rats / A restrição alimentar desde a lactação reduziu a ansiedade em ratos Wistar adultos

ABSTRACT Objective To evaluate the effects of macronutrients (protein, carbohydrate and/or lipid) in the diet of young adult (72 days) and adult (182 days) Wistar rats treated ad libitum and with 30% restriction from birth on anxiety in the elevated plus-maze. Methods We used 238 rats treated from birth, composing the groups: Control, Protein, Carbohydrate, Lipid, Carbohydrate and Lipid, Control Restriction, Protein Restriction, Carbohydrate Restriction, Lipid Restriction and Carbohydrate and Lipid Restriction. The animals were weighed at the beginning and at the end of the experiment and tested in the elevated plus-maze. Data were submitted to analysis of variance, followed by the Newman-Keuls Test (p<0.05). Results Among the animals treated ad libitum, the Control, Carbohydrate plus Lipid and Lipid gained more weight than the Carbohydrate and Protein; ad libitum animals gained more weight than those on restriction; among the restrictions, Carbohydrate Restriction rats were the ones that gained less weight. Diet-restricted animals exhibited reduced first-entry latency, greater percentage of entries and time spent, frequency of open arm extremity visits, head dipping (protected and unprotected), and length of stay in the central area of the elevated plus-maze. The animals with 182 days presented greater latency for first entry, reduced frequency of false entries and visits to the ends of the open arms and protected head dipping. Conclusion Food restricted animals, regardless of the macronutrient present in the diet, were less anxious and/or increased their impulsivity and those at 182 days were more anxious and/or with reduced impulsivity.

RESUMO Objetivo Este estudo buscou avaliar os efeitos dos macronutrientes (proteína, carboidrato e/ou lipídeos) na alimentação de ratos Wistar adultos jovens (72 dias) e adultos (182 dias) tratados ad libitum e com restrição a 30% desde o nascimento quanto à ansiedade através do labirinto em cruz elevado. Métodos Foram utilizados 238 ratos tratados desde o nascimento, compondo os grupos Controle, Proteína, Carboidrato, Lipídeos, Carboidrato e Lipídeos, Restrição Controle, Restrição Proteína, Restrição Carboidrato, Restrição Lipídeos e Restrição Carboidrato e Lipídeos. Os animais foram pesados no início e no final do experimento e testados no labirinto em cruz elevado. Os dados foram submetidos à análise de variância, seguida do teste de Newman-Keuls (p<0,05). Resultados Entre os animais tratados ad libitum, os dos grupos Controle, Carboidrato e Lipídeos, e Lipídeos ganharam mais peso do que os Carboidrato e Proteína; os ad libitum ganharam mais peso do que os de restrição; os Restrição Carboidrato foram os que ganharam menos peso. Animais alimentados com restrição de dieta apresentaram menor latência de primeira entrada, maior porcentagem de entradas e de tempo gasto, frequência de visitas às extremidades dos braços abertos, de mergulho (protegido e desprotegido) e tempo de permanência na área central do labirinto em cruz elevado. Os animais com 182 dias demonstraram maior latência para primeira entrada, menor frequência de falsas entradas e visitas às extremidades dos braços abertos e mergulho protegido. Conclusão Os animais em restrição alimentar, independentemente do macronutriente presente na dieta, foram menos ansiosos e/ou mais impulsivos, e os com 182 dias foram mais ansiosos e/ou menos impulsivos.

The Effects of Meal Timing and Frequency, Caloric Restriction, and Fasting on Cardiovascular Health: an Overview

Cardiovascular disease (CVD), which is the leading cause of death worldwide, is strongly affected by diet. Diet can affect CVD directly by modulating the composition of vascular plaques, and indirectly by affecting the rate of aging. This review summarizes research on the relationships of fasting, meal timing, and meal frequency with CVD incidence and progression. Relevant basic research studies, epidemiological studies, and clinical studies are highlighted. In particular, we discuss both intermittent and periodic fasting interventions with the potential to prevent and treat CVD.

Adipose tissue is less responsive to food restriction anti-inflammatory effects than liver, muscle, and brain in mice

High caloric intake promotes chronic inflammation, insulin resistance, and chronic diseases such as type-2 diabetes, which may be prevented by food restriction (FR). The effect of FR on expression of pro-inflammatory and anti-inflammatory genes in adipose tissue, liver, muscle, and brain was compared. Male Swiss mice were submitted to FR (FR group) or had free access to food (control group) during 56 days. The liver, gastrocnemius muscle, brain, and epididymal white adipose tissue (WAT) were collected for analysis of gene expressions. FR attenuated inflammation in the liver, brain, and gastrocnemius muscle but did not markedly change inflammatory gene expression in epididymal WAT. We concluded that adipose tissue was less responsive to FR in terms of gene expression of pro-inflammatory and anti-inflammatory genes.

Fasting and caloric restriction in cancer prevention and therapy / 肿瘤

Cancer is the second cause for human death. The incidence of cancer is increasing with the expansion of the elder population and the increase of risk factors such as smoking, obesity and unhealthy life style. The present interventions to prevent and treat cancers are largely ineffective, so the novel strategy for cancer prevention and therapy is needed. Recently, fasting and caloric restriction are found to be beneficial for cancer prevention and therapy. This review aims to summarize the major progresses of fasting and caloric restriction in cancer research, which will shed light on the cancer prevention and therapy.

Effect and mechanism of caloric restriction on early social isolation-induced cognitive impairment in mice / 解剖学报

Objective: To investigate the effect and mechanism of caloric restriction (CR) on early social isolation (SI) induced cognitive dysfunction in mice. Methods: Thirty-six kunming mice (3-weeks old) were randomly divided into group house (GH, n= 12), early socially isolated (SI, n= 12), caloric restriction and socially isolated (SI+CR, n= 12). The GH group (6 mice/cage) and SI group (1 mice/cage) were reared separately under the same conditions, while the SI+CR group (1 mice/cage) were given food every other day. The open field experiment was used to measure the locomotive of mice; The object recognition task was used to evaluate the cognitive function; The expression of microglial marker ionized calcium-binding adapter molecule 1 (IBA-1) in hippocampus was detected by immunohistochemistry. The expression of microglial activation marker CD68 and interleukin-lÎ2 (IL-lÎ2) in hippocampus was detected by Western blotting. Results: In the open field test, there was no difference in the activity of the three groups of mice. Compared with the GH group, the SI group showed significantly reduced discrimination ratio in object recognition task, with remarkably upregulated expression of IL-1Î2 in hippocampus (P<0. 01). In addition, SI group exhibited over-activated microglia in hippocampus indicated by increased number of IBA-1-positive cells and high expression of CD68 (P<0.01). Compared with the SI group, SI+CR group enhanced discrimination ratio in object recognition task, with down-regulated expression of IL-1Î2 in hippocampus (P<0. 01), and the number of IBA-1-positive cells and the expression of CD68 significantly reduced (P<0. 01). Conclusion: Caloric restriction alleviates Si-induced cognitive dysfunction, which might be attributed to the inhibiting of microglia activation in the hippocampus.

Effects of caloric restriction on the expression of lipocalin-2 and its receptor in the brown adipose tissue of high-fat diet-fed mice

Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.

Restricción alimentaria intermitente: repercusiones en la regulación de la homeostasis energética hipotalámica y tejido adiposo / Intermittent food restriction: repercussions in the regulation of hypothalamic energy homeostasis and adipose tissue

La práctica de restricción alimentaria intermitente (RAI) bien como sus variaciones, es utilizada por individuos con intensión de pérdida de masa corporal. Existen evidencias científicas favorables a esta práctica; no obstante, son insuficientes los estudios que muestren las consecuencias a largo plazo y sus repercusiones en el control de la homeostasis energética en el sistema nervioso central (SNC). Considerando su creciente utilización, tanto como su recomendación y además de la controversia existente en la bibliografía, la presente revisión tiene como objetivo mostrar los efectos de la RAI sobre la regulación central de la homeostasis energética registrados en la literatura.

The practice of intermittent food restriction (IFR) along its variations, is used by individuals with an intentional loss of body mass. There is scientific evidence favorable to this practice; however, studies showing the long term consequences and their impact on the control of energy homeostasis at the level of the central nervous system (CNS) are insufficient. Considering the increase in its use, as well as in its recommendation and the great controversy existing in the bibliography, the present review aims to show the effects of RAI on the central regulation of energy homeostasis reported in the literature.

Fasting/Refeeding Cycles Prevent Myocardial Dysfunction and Morphology Damage in the Spontaneously Hypertensive Rats / Ciclos de Jejum/Realimentação Previnem Disfunção Miocárdica e Danos Morfológicos em Ratos Espontaneamente Hipertensos

Abstract Background: Caloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown. Objective: To investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca2+ handling and b-adrenergic system. Methods: Sixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R50) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% (a = 0.05). Results: The RF rats presented lower cardiac atrophy than R50 in relation to C rats. The C rats increased weight gain, R50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R50 rats. In addition, the R50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils. Conclusion: Fasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca2+ handling and b-adrenergic system.

Resumo Fundamento: A restrição calórica compromete a função e a morfologia cardíacas em corações hipertrofiados de ratos espontaneamente hipertensos (SHR). No entanto, a influência de ciclo de jejum/Realimentação é desconhecida. Objetivo: Investigar o efeito de ciclos de jejum/realimentação sobre a remodelação e função miocárdica. Além disso, o presente estudo foi desenhado para avaliar os mecanismos subjacentes à participação do trânsito de cálcio (Ca+2) e sistema beta-adrenérgico. Métodos: Neste estudo, SHR machos de 60 dias de idade foram submetidos a alimento ad libitum (grupo C), 50% de restrição alimentar (grupo R50) ou ciclos de RF (grupo RF) por 90 dias. A remodelação cardíaca foi avaliada por meio da análise ultraestrutural e função do músculo papilar isolado. Adotou-se o nível de significância de 5% (a = 0,05). Resultados: Os ratos do grupo RF apresentaram menor atrofia cardíaca do que os do grupo R50 em relação aos do grupo C. Os ratos do grupo C aumentaram peso corporal, os ratos do grupo R50 mantiveram seu peso corporal inicial e os ratos do grupo RF aumentaram e reduziram seu peso durante o ciclo RF. O ciclo RF não causou comprometimento funcional, pois os parâmetros isotônicos e isométricos apresentaram comportamento similar aos dos ratos do grupo C. Os parâmetros cardíacos isotônicos e isométricos mostraram-se significativamente elevados nos ratos do grupo RF em comparação aos dos ratos do grupo R50. Além disso, os ratos do grupo R50 apresentaram dano cardíaco em comparação aos ratos do grupo C quanto às variáveis isotônicas e isométricas. Os ratos do grupo R50 apresentaram alterações focais em muitas fibras musculares, enquanto os ratos do grupo RF apresentaram leves alterações, como perda ou desorganização de miofibrilas. Conclusão: Ciclos de Jejum/Realimentação promovem efeitos benéficos cardíacos e atenuam o dano miocárdico causado por restrição calórica em SHR, contribuindo para reduzir o risco cardiovascular e os danos morfológicos. Além disso, o ciclo de jejum/realimentação promove leve melhora do trânsito do Ca2+ e do sistema beta-adrenérgico.

The truth about artificial sweeteners – Are they good for diabetics?

Artificial sweeteners are thought to be beneficial for diabetics or obese where refined sugar can be a problem. These low-calorie sweeteners are seemingly safe to use, provide sweetness without calories, and provide a choice of sweet foods to those who otherwise cannot partake them (refined sugars). However, while artificial sweeteners may indeed restrict calories most of them have no beneficial effects on control of diabetes mellitus; rather possibly increase its risk. Additionally, there could be some other safety concerns possibly risk of cancer.

Interleukin-12 as a biomarker of the beneficial effects of food restriction in mice receiving high fat diet or high carbohydrate diet

The impact of food restriction (FR) during 56 days on serum levels of cytokines in mice fed a high-fat diet (HFD) or high-carbohydrate diet (HCD) were evaluated. The amount of food was reduced 50% for HFD-FR and HCD-FR groups compared to mice receiving free access to HFD (HFD group) or HCD (HCD group). We quantified the serum levels of basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, inducible protein 10, interferon γ, interleukin 1α (IL-1α), IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, keratinocyte chemoattractant, macrophage inflammatory protein-1α, monocyte chemotactic protein 1, monokine induced by IFN-γ, and tumor necrosis factor α. Only IL-12 levels were lower (P<0.05), for both HFD-FR (HFD-FR vs HFD) and HCD-FR (HCD-FR vs HCD). Therefore, IL-12 levels could be considered a biological marker of the beneficial effects of FR.

Reactivation of visual cortical plasticity by caloric restriction mediated by AMPK-SIRT1 pathway from monocular deprivation in adult mice / 中华实验眼科杂志

Objective This study was to investigate the effect of caloric restriction on the plasticity of visual cortex in adult monocular deprivation (MD) amblyopic mice,as well as to promote the treatment of amblyopia,and to explore the possible molecular mechanism of this benefical effect.Methods Fifty healthy newborn Kunming mice of clean grade were randomly divided into 3 groups using a random number table method:normal control group (n =14),MD+ ad libitum group (n=18) and MD+ caloric restriction group (n=18).A mouse model of adult MD amblyopia was established,and caloric restriction intervention and ad libitum were performed on MD + caloric restriction group and MD+ ad libitum group,respectively.The visual acuity and flash visual evoked potential (F-VEP) of each group were detected.The synaptic structure of visual cortex neurons was observed by transmission electron microscope,and the expression of phosphorylated AMP-activated protein kinase-α(p-AMPKα) and silent information regulator 1 (SIRT1) in visual cortex were detected by Western blot.The animal feeding and use was in accordance with the standards set by the ARVO.Results The weight of mice in MD+ caloric restriction group increased from the beginning of the first week,and was significantly lower than that in the MD + ad libitum group (P＜0.05).Compared with the MD+ ad libitum group,the visual acuity was restored,the latency was shortened,and the amplitude of F-VEP was increased in the deprived eyes of MD+ caloric restriction group (all at P＜0.05).Transmission electron microscope observation showed that the width of synaptic gap of visual cortical neurons was significantly narrower,and the thickness of postsynaptic density was significantly thicker in MD+ caloric restriction group than that in the MD+ ad libitum group (both at P＜0.05);compared with the normal control group,the synaptic gap was widened and the postsynaptic density was significantly thicker than that in the MD+ ad libitum group (both at P＜0.05).Western blot showed that the expression of p-AMPKα in visual cortex in the normal control group,MD+ caloric restriction group and MD+ ad libitum group was 0.89±0.03,0.94±0.02 and 0.74 ±0.02,and the expression of SIRT1 was 0.97±0.11,0.95±0.14 and 0.58±0.13,respectively,showing significant differences among the three groups (F =14.57,P =0.00;F=23.91,P=0.00),the expressions of p-AMPKα and SIRT1 in visual cortex were increased in MD+ caloric restriction group than those in M D+ ad libitum group (both at P＜0.05).Conclusions Caloric restriction can restore the ultrastructure of synapses and improve the visual cortical plasticity in adult MD mice,so that help to improve visual function.Its mechanism may be related to the activation of AMPK-SIRT1 pathway.