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Resumen Introducción: la obesidad representa una importante problemática a nivel mundial, esto genera la necesidad de encontrar nuevas estrategias terapéuticas que contribuyan a tratar dicha enfermedad. En los últimos años, ha surgido el ayuno intermitente (AI) como una posible alternativa dietoterápica en el descenso de peso y en la mejora de variables cardiometabólicas, aunque la evidencia científica es controvertida. Objetivos: evaluar la evidencia científica disponible respecto a la efectividad del ayuno intermitente en el descenso de peso y en la mejora de las variables cardiometabólicas en comparación con la restricción energética continua. Materiales y Método: se ha llevado a cabo una búsqueda sistemática de ensayos clínicos aleatorizados (ECA) en las bases de datos PUBMED y Cochrane Library. Se incluyeron 11 ECA, que compararan AI con restricción energética continua (REC) con un rango de duración de 4 a 48 semanas, en mujeres y hombres con un índice de masa corporal (IMC) ≥25 kg/m2 y que hayan evaluado descenso de peso y variables cardiometabólicas. Resultados: el AI presentó una mediana de descenso de peso de 5,5 kg (RIQ: 4,7;6,86 kg), mientras que para la REC fue de 4,8 kg (RIQ: 3,8;6,6 kg). El IMC, la masa grasa, la masa libre de grasa y circunferencia de cintura, se redujeron de manera significativa tanto para la intervención como para el comparador. Asimismo, las variables cardiometabólicas presentaron mejoras respecto a los valores iniciales, sin embargo, evidenciaron resultados heterogéneos. Conclusiones: tanto el AI como la REC resultaron ser efectivas para la mejora de las variables estudiadas. La intervención no demostró ser mejor que el comparador.

Abstract Introduction: obesity represents a major problem worldwide, and this generates the need to find new therapeutic tools that contribute to the treatment of this disease. In recent years, intermittent fasting (IF) has emerged as a possible dietary alternative in weight loss and improvement of cardiometabolic variables, although the scientific evidence is controversial. Objectives: to evaluate the available scientific evidence regarding the effectiveness of intermittent fasting in weight loss and in the improvement of cardiometabolic variables in comparison with continuous energy restriction. Materials and Method: a systematic search of PUBMED and Cochrane Library databases for randomized clinical trials (RCTs) has been conducted. Eleven RCTs were included, comparing IF with continuous energy restriction (CER) with a duration range of 4 to 48 weeks, in women and men with a body mass index (BMI) ≥25 kg/m2 and who assessed weight loss and cardio metabolic variables. Results: the IF presented a median weight loss of 5.5 kg (IQR:4.7; 6.86 kg), while for CER it was 4.8 kg (IQR: 3.8; 6.6 kg). BMI, fat mass, fat-free mass, and waist circumference were significantly reduced for both the intervention and the comparator. Likewise, the cardiometabolic variables presented improvements with respect to the initial values, however, they showed heterogeneous results. Conclusions: both IF and CER proved to be effective in improving the variables studied; the intervention did not prove to be better than the comparator.

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BACKGROUND & AIMS: Time-restricted feeding (TRF) studies usually are of short-term, involving heterogeneous populations, without a control group with similar energy restriction. Besides, it seldom assess vital signs such as body temperature and heart rate, which may be influenced by the fasting state. In this investigation, we assessed the long-term effects of TRF on body weight, body composition and vital signs of low-income women with obesity undergoing diets with the same energy deficit. METHODS: Low-income women with obesity were randomly allocated to a group with a hypoenergetic diet and 12 h of TRF or to a group with only a hypoenergetic diet, for 12 months. Body fat and waist circumference were estimated using a tetrapolar electrical bioimpedance and an inelastic measuring tape, respectively, at baseline and after 4, 6 and 12 months of intervention. Systolic and diastolic blood pressure, heart rate, and axillary temperature were measured at baseline and 12 months of intervention. The energy content of the diets was determined based on the women's resting metabolic rate (by indirect calorimetry) and level of physical activity (by triaxial accelerometers). Effects were analyzed using an intention-to-treat approach. RESULTS: Fifty-eight women were randomized and 31 (53.44%) were lost to follow-up at 12 months. Dropout rates were similar between groups. In the intention-to-treat analysis, there were no significant changes in the body weight after 12 months (Differences in changes from baseline between groups: -0.05 95%CI [-2.34; 2.24] Kg; p = 0.96). An increase in axillary temperature (0.40 °C, 95% CI [-0.14; 0.67]°C, p < 0.01), a reduction in the percentage of body fat (-1.64%, 95% CI [-3.08; -0.19]%, p = 0.02) and waist circumference (-2.57 cm, 95% CI [-5.73; 0.58] cm, p = 0.03 in the mixed model involving 4 measurements) were observed in the intervention group, when compared to the control group. CONCLUSIONS: TRF showed no effects on weight loss. Nevertheless the findings on waist circumference and body fat, although not clinically meaningful, suggest that this strategy may help in the long-term management of obesity in this population, since it is an easy to apply intervention. Axillary temperature findings warrants further investigation. Registered under www.ensaiosclinicos.gov.br Identifier no. RBR-387v6v. TRIAL REGISTRATION: http://www.ensaiosclinicos.gov.br/rg/RBR-387v6v/.

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PURPOSE OF REVIEW: Diet is a pillar of type 2 diabetes mellitus (T2DM) management. Intermittent fasting (IF) is postulated as a novel approach, able to improve glucose control and potentially capable of reversing some of the pathophysiological alterations of this condition. In this review, the molecular and clinical evidence of diets based on intermittent energy restriction (IER) in laboratory animal models and subjects with type 2 diabetes is discussed. The mechanisms through which IF are thought to improve glucose homeostasis and reverse ß cell failure are also reviewed. RECENT FINDINGS: Studies derived from murine models suggest that IER is associated with improvements in ß cell function and insulin resistance. Two main mechanisms have been demonstrated, one derived from the autophagy-lysosome pathway and, the other from an increase in neurogenin3 (Ngn3) levels (a marker for endocrine progenitor cells like ß cells during development). Notably, IER also promotes reconstruction of gut microbiota. In mice, all effects were independent of weight loss. By contrast, in human studies, outcomes are widely attributable to weight loss. The more consistent results are reductions in body weight, visceral fat, and glucose and insulin levels. Increases in HDL cholesterol levels are also frequently reported. The decrease in insulin levels observed in humans is in opposition with the increase reported in mice, suggesting that the main mechanism in humans is an improvement in peripheral insulin action. Recommending diets based on intermittent fasting in humans is based on the promising results found in animal models where an improvement in ß cell function has been recorded. ß cell function after IF has not been assessed in human subjects with T2DM. This review provides information regarding different protocols for the implementation of IF in diabetic persons and also provides important safety advice in order to avoid adverse effects. Clinical studies do not show an increased risk of hypoglycemia, and a recent case series reported reversal of T2DM.

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Abstract Aim: To investigate the effect of moderate-intensity swimming training on bone mineral density under a 20% food restriction (FR) schedule for 12 weeks in female rats. Methods: Forty female Wistar rats were distributed into four groups: control (CG), exercised (EG), food restriction (FRG), and food restriction/exercised (FREG). At 95 days. the animals were subjected to aquatic adaptation and then performed the critical load test to individually determine the critical load intensity (CLi, % of body mass). Exercised groups swam 5 days a week, 30 minutes daily with weekly adjustment of the load equivalent to 80% of the CLi. The FR schedule was 20% in relation to CG and started concomitantly with physical training (PT). After 12 weeks, visceral fat weight was recorded and the femur was collected for biophysical and biomechanical analysis. Results: FR and exercise training promoted visceral fat reduction (p<0.01). FR reduced bone mineral density (p<0.01), while exercise training prevented such reduction. On the other hand, FR and exercise training did not promote significant changes in biomechanical parameters of the femur. Conclusion: Exercise training at moderate intensity was efficient in preserving bone mineral density despite long term of FR at 20%.

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Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of an array of enzymes with important detoxifying and antioxidant functions. Current findings support the role of high levels of oxidative stress in the pathogenesis of neurological disorders. Given the central role played by Nrf2 in counteracting oxidative damage, a number of studies have targeted the modulation of this transcription factor in order to confer neuroprotection. Nrf2 activity is tightly regulated by oxidative stress and energy-based stimuli. Thus, many dietary interventions based on energy intake regulation, such as dietary energy restriction (DER) or high-fat diet (HFD), modulate Nrf2 with consequences for a variety of cellular processes that affect brain health. DER, by either restricting calorie intake or meal frequency, activates Nrf2 thereby triggering its protective effects, whilst HFD inhibit this pathway, thereby exacerbating oxidative stress. Consequently, DER protocols can be valuable strategies in the management of central nervous system (CNS) disorders. Herein, we review current knowledge of the role of Nrf2 signaling in neurological diseases, namely Alzheimer's disease, Parkinson's disease, multiple sclerosis and cerebral ischemia, as well as the potential of energy intake regulation in the management of Nrf2 signaling.

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Surveys report that 25-57 % of cats are overweight or obese. The most evinced cause is neutering. Weight loss often fails; thus, new strategies are needed. Obesity has been associated with altered gut bacterial populations and increases in microbial dietary energy extraction, body weight and adiposity. This study aimed to determine whether alterations in intestinal bacteria were associated with obesity, energy restriction and neutering by characterising faecal microbiota using 16S rRNA gene sequencing in eight lean intact, eight lean neutered and eight obese neutered cats before and after 6 weeks of energy restriction. Lean neutered cats had a bacterial profile similar to obese rodents and humans, with a greater abundance (P<0·05) of Firmicutes and lower abundance (P<0·05) of Bacteroidetes compared with the other groups. The greater abundance of Firmicutes in lean neutered cats was due to a bloom in Peptostreptococcaceae. Obese cats had an 18 % reduction in fat mass after energy restriction (P<0·05). Energy reduction was concurrent with significant shifts in two low-abundance bacterial genera and trends in four additional genera. The greatest change was a reduction in the Firmicutes genus, Sarcina, from 4·54 to 0·65 % abundance after energy restriction. The short duration of energy restriction may explain why few bacterial changes were observed in the obese cats. Additional work is needed to understand how neutering, obesity and weight loss are related to changes in feline microbiota and how these microbial shifts affect host physiology.

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Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance. 1356 proteins were identified and 348 quantified while 127 metabolites were quantified. The restricted hypothalamus showed down-regulation of 36 proteins and 5 metabolites and up-regulation of 21 proteins and 9 metabolites. Integrated pathway analysis of the proteomics and metabolomics data indicated impairment of hypothalamic glucose metabolism, increased flux through the hexosamine pathway, deregulation of TCA cycle and the respiratory chain, and alterations in glutathione metabolism. The data suggest IUGR modulation of energy metabolism and redox homeostasis in the hypothalamus of male adult rats. The present results indicated deleterious consequences of IUGR on hypothalamic pathways involved in pivotal physiological functions. These results provide guidance for future mechanistic studies assessing the role of intrauterine malnutrition in the development of metabolic diseases later in life.

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Steroid hormones, such as sex hormones and glucocorticoids, have been demonstrated to play a role in different cellular processes in the central nervous system, ranging from neurodevelopment to neurodegeneration. Environmental factors, such as calorie intake or fasting frequency, may also impact on such processes, indicating the importance of external factors in the development and preservation of a healthy brain. The hypothalamic-pituitary-adrenal axis and glucocorticoid activity play a role in neurodegenerative processes, including in disorders such as in Alzheimer's and Parkinson's diseases. Sex hormones have also been shown to modulate cognitive functioning. Inflammation is a common feature in neurodegenerative disorders, and sex hormones/glucocorticoids can act to regulate inflammatory processes. Intermittent fasting can protect the brain against cognitive decline that is induced by an inflammatory stimulus. On the other hand, obesity increases susceptibility to inflammation, while metabolic syndromes, such as diabetes, are associated with neurodegeneration. Consequently, given that gonadal and/or adrenal steroids may significantly impact the pathophysiology of neurodegeneration, via their effect on inflammatory processes, this review focuses on how environmental factors, such as calorie intake and intermittent fasting, acting through their modulation of steroid hormones, impact on inflammation that contributes to cognitive and neurodegenerative processes.

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Nutritional intervention for weight loss is one of the treatment options for obstructive sleep apnoea (OSA) in patients with overweight or obesity. However, the effects of moderate energy restriction on OSA severity are not yet known. The present study aimed to evaluate the effects of moderate energy restriction on OSA severity and CVD risk factors in obese patients with OSA. In this 16-week randomised clinical trial, twenty-one obese subjects aged 20-55 years and presenting an apnoea/hypopnoea index (AHI)≥5 events/h were randomised into two groups: the energy restriction group (ERG) and the control group (CG). The ERG was instructed to follow an energy-restricted diet -3347·2 kJ/d (-800 kcal/d) and the CG was advised not to change their food intake. At the beginning and at the end of the study, participants underwent evaluation of the following: OSA (Watch-PAT200®), nutritional parameters, blood pressure, sympathetic activity, inflammatory biomarkers, metabolic profile and endothelial function. The ERG (n 11), compared with the CG (n 10), had a significantly greater reduction in body weight (Cohen's d=-1·19; P<0·001), in AHI (Cohen's d=-0·95; P=0·04) and in plasma concentrations of adrenaline (Cohen's d=-1·02; P=0·04) as well as a significantly greater increase in minimum O2 saturation (Cohen's d=1·08; P=0·03). Although energy restriction was not associated with significant improvements in CVD risk factors, medium-to-large effect sizes were observed, suggesting that the statistically non-significant difference between groups may be due to the small sample size. This study suggests that in obese patients with OSA, moderate energy restriction is able to reduce the parameters of OSA severity and sympathetic activity.

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BACKGROUND: Lack of weight gain throughout adult life could mimic the beneficial effects of energy restriction in humans. The present study aimed to assess the effects of weight stability or gain, over a period of 10 years, on telomere length, sirtuin 1 and 6 expression, and carotid intima media thickness. METHODS: We studied 148 healthy adults (age range 20-59 years; 101 females) who had an objective record of their weight 10 years before. They were classified as weight losers, weight maintainers, weight gainers and extreme weight gainers. A fasting blood sample was obtained for routine laboratory and isolation of peripheral blood mononuclear cells, to extract DNA and RNA, and to measure telomere length and sirtuin 1 and 6 expression, respectively. Carotid intima media thickness was measured by ultrasound. Body composition was measured by Dual-energy X-ray absorptiometry. RESULTS: In the 10-year period, 24 participants lost weight (17 females), 65 maintained weight (41 females), 25 gained weight (15 females) and 34 were extreme weight gainers (28 females). Female weight gainers had a higher body mass index, waist circumference, total body fat and homeostatic model assessment insulin resistance. Male weight gainers had a higher hip circumference and total body fat. No differences in telomere length, sirtuin 1 expression and carotid intima media thickness were observed between weight gainers and maintainers. CONCLUSIONS: No effect of weight maintenance or gain was observed on metabolic and vascular markers of ageing.

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