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The relationship between protein and energy and their appropriate proportions in hyperphenylalaninemia (HPA) or phenylketonuria (PKU) patients in terms of growth have been poorly studied, especially in those diagnosed late. We aimed to describe the protein energy ratio (P:E) and its association with body mass index (BMI) in 638 dietetic and anthropometric assessments from 54 early- or late-diagnosed HPA/PKU patients. Dietetic and anthropometric data were analyzed and classified according to BMI Z-Score and type of diagnosis, early by newborn screening (NBS) or late. Correlation between BMI Z-Score and P:E ratio was established. Percent of dietary protein from Phe-free metabolic formula was analyzed. According to the BMI Z-Score, the majority of assessments were eutrophic (69.4%). The median P:E ratio was >4 in most of the overweight assessments. Remarkably, the underweight group consumed the highest proportion of Phe-free metabolic formula (74.5%). A positive correlation between BMI Z-Score and P:E ratio was found. The highest proportion of underweight was found in the late-diagnosed patients. Our findings might be related to their nutritional history previous to the HPA/PKU treatment. Thus, complex nutritional outcome of the late-diagnosed HPA/PKU patients deserves actions to guarantee the early diagnosis, closer nutritional follow-up and alternative therapeutic approaches.

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GPR139 is an orphan G-protein-coupled receptor that is expressed in restricted areas of the nervous system, including the hypothalamus. In this study, we hypothesized that GPR139 could be involved in the regulation of energy balance and metabolism. In the first part of the study, we confirmed that GPR139 is expressed in the hypothalamus and particularly in proopiomelanocortin and agouti-related peptide neurons of the mediobasal hypothalamus. Using a lentivirus with a short-hairpin RNA, we inhibited the expression of GPR139 bilaterally in the mediobasal hypothalamus of mice. The intervention promoted a 40% reduction in the hypothalamic expression of GPR139, which was accompanied by an increase in body mass, a reduction in fasting blood glucose levels, and an increase in insulin levels. In the hypothalamus, inhibition of GPR139 was accompanied by a reduction in the expression of orexin. As previous studies using a pharmacological antagonist of orexin showed a beneficial impact on type 2 diabetes and glucose metabolism, we propose that the inhibition of hypothalamic GPR139 could be acting indirectly through the orexin system to control systemic glucose and insulin. In conclusion, this study advances the characterization of GPR139 in the hypothalamus, demonstrating its involvement in the regulation of body mass, blood insulin, and glycemia.

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Few studies have investigated which types of food are least reported among underreporters of energy intake (EI). This study assessed the association between the underreporting of EI and the consumption report of food groups according to NOVA classification in women in social vulnerability. EI was measured through three 24-h dietary recalls administered by the research team. Total energy expenditure (TEE) was evaluated using the doubly labelled water method. The percentage of EI arising from each NOVA group food classification (unprocessed/minimally processed foods, culinary ingredients, processed foods and ultra-processed foods [UPF]) was calculated. The agreement between the EI and the TEE was assessed using the ratio EI:TEE. Associations were assessed with Pearson's correlation and multivariable linear regression, adjusted for age, education and body fat. The sample (63 women, age: 30.8 years, Body Mass Index: 27.6 kg/m2 ) reported an EI of 1849 kcal and a TEE of 2223 kcal, with a mean EI:TEE of 0.85. There were no significant correlations between the EI:TEE and the reported food intake according to NOVA classifications. Multivariable linear regression also did not show any significant associations (UPF: 8.47, 95% CI: [-3.65; 20.60] %kcal; Processed: -6.85, [-19.21; 7.71] %kcal; Culinary ingredients: 1.30 [-5.10; 7.71] %kcal; Unprocessed/minimally processed: -2.92 [-10.98; 5.13] %kcal). In conclusion, socially vulnerable women that underreport their EI do not report a lower intake of any specific group of foods according to NOVA classification.

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Currently, up to 35% off all drugs approved for the treatment of human diseases belong to the G-protein-coupled receptor (GPCR) family. Out of the almost 800 existing GPCRs, 25% have no known endogenous ligands and are regarded as orphan receptors; many of these are currently under investigation as potential pharmacological targets. Here, we hypothesised that orphan GPCRs expressed in the hypothalamus could be targets for the treatment of obesity and other metabolic diseases. Using bioinformatic tools, we identified 78 class A orphan GPCRs that are expressed in the hypothalamus of mice. Initially, we selected two candidates and determined their responsivities to nutritional interventions: GPR162, the GPCR with highest expression in the hypothalamus, and GPR68, a GPCR with intermediate expression in the hypothalamus and that has never been explored for its potential involvement in metabolic regulation. GPR162 expression was not modified by fasting/feeding or by the consumption of a high-fat diet, and was therefore not subsequently evaluated. Conversely, GPR68 expression increased in response to the consumption of a high-fat diet and reduced under fasting conditions. Using immunofluorescence, GPR68 was identified in both proopiomelanocortin-expressing and agouti-related peptide-expressing neurons in the hypothalamic arcuate nucleus. Acute inhibition of GPR68 with an allosteric modulator promoted an increase in the expression of the orexigenic agouti-related peptide and neuropeptide Y, whereas 4- and 12-h inhibition of GPR68 resulted in increased caloric intake. Thus, GPR68 has emerged as an orphan GPCR that is expressed in the hypothalamus and is involved in the regulation of feeding.

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Orexin-A, a hormone secreted by orexin neurons, is involved in caloric-intake regulation. Current understanding is based primarily on animal studies. Studies of orexin in humans are scarce, and to our knowledge there are no prior studies in adolescents. We studied fasting Orexin-A levels related to energy intake at breakfast and a subsequent snack in adolescents (n = 668) from a longitudinal study in Chile. Body-Mass Index (BMI), components of the metabolic syndrome and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured. Energy intake was calculated based on food weights before and after the standardized breakfast and subsequent snack. High energy intake was defined as ≥ 75th percentile. We assessed the relationship between orexin-A and high energy intake, adjusting for confounders. Higher orexin levels were associated with high breakfast energy intake (OR: 1.21; 95%CI: 0.98-1.49). Conversely, those with higher orexin levels showed a non-significant trend for lower odds of high energy intake for the snack (OR: 0.87; 95%CI: 0.70-1.07). There was a significant interaction between high breakfast energy intake and orexin levels. Those who ate more calories at breakfast displayed a lower inhibitory effect of orexin on eating at the snack (p < 0.05). There was no significant interaction between weight status and orexin. In conclusion, orexin-A levels were associated with breakfast energy intake and inversely related with subsequent snack energy intake in participants whose caloric intake at breakfast was within the normal range. Based on these findings, it appears that the association of orexin-A with energy intake depends on eating behavior.

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Orexin-A, a hormone secreted by orexin neurons, is involved in caloric-intake regulation. Current understanding is based primarily on animal studies. Studies of orexin in humans are scarce, and to our knowledge there are no prior studies in adolescents. We studied fasting Orexin-A levels related to energy intake at breakfast and a subsequent snack in adolescents (n = 668) from a longitudinal study in Chile. Body-Mass Index (BMI), components of the metabolic syndrome and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured. Energy intake was calculated based on food weights before and after the standardized breakfast and subsequent snack. High energy intake was defined as ≥ 75th percentile. We assessed the relationship between orexin-A and high energy intake, adjusting for confounders. Higher orexin levels were associated with high breakfast energy intake (OR: 1.21; 95%CI: 0.98-1.49). Conversely, those with higher orexin levels showed a non-significant trend for lower odds of high energy intake for the snack (OR: 0.87; 95%CI: 0.70-1.07). There was a significant interaction between high breakfast energy intake and orexin levels. Those who ate more calories at breakfast displayed a lower inhibitory effect of orexin on eating at the snack (p < 0.05). There was no significant interaction between weight status and orexin. In conclusion, orexin-A levels were associated with breakfast energy intake and inversely related with subsequent snack energy intake in participants whose caloric intake at breakfast was within the normal range. Based on these findings, it appears that the association of orexin-A with energy intake depends on eating behavior.

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A doença crítica promove um estado hipercatabólico associado a uma resposta inflamatória intensa. Admite-se que essas alterações contribuem para o aumento do gasto de energia e para a elevação do catabolismo proteico. Objetivo: analisar a adequação calórico-proteica da terapia de nutrição enteral e o seu impacto no desfecho clínico de pacientes críticos. Método: Trata-se de um estudo longitudinal prospectivo realizado com 36 pacientes internados em unidades de terapia intensiva. A adequação da oferta calórico-proteica foi obtida pela relação percentual a partir do quarto dia de implementação da terapia nutricional. Realizou-se o teste de Shapiro Wilk para averiguar a normalidade dos dados e a partir disso, foi aplicado o teste de Mann-Whitney ou de t-Student não pareado. Foi realizada a análise de regressão logística com estimativa de seu coeficiente. Para a regressão estimou-se o intervalo de confiança de 95% e nível de significância de 5%. Foi utilizado o software STATA® versão 14.0 nesta análise. Resultados: Ao avaliar 36 pacientes verificou-se que a sobrevida foi menor entre os indivíduos que apresentaram o menor percentual de adequação calórica (p=0,010) e proteica (p=<0,001). Observou-se que oferta proteica impactou mais expressivamente os desfechos clínicos, ao aumento de 1% na média de adequação proteica as chances de óbito diminuíram 21%. Conclusão: O menor percentual de adequação calórico-proteica foi associado a menor sobrevida de pacientes críticos. Ainda, observou-se que o percentual de adequação proteica se associou mais expressivamente aos desfechos clínicos nessa amostra

The critical illness promotes a hypercatabolic state associated with an intense inflammatory response. It is recognized that those changes contribute to the rise of consumption of energy expenditure and to protein metabolism rise. Objective: to analyze the adequacy caloric-protein of enteral nutrition therapy and its impact on the clinical outcome of critical patients. Method: This is a prospective longitudinal study conducted with 36 hospitalized patients in intensive care units. The caloric-protein adequacy was acquired by percent ratio from the fourth day of nutritional therapy implementation. The Shapiro Wilk test was performed to check the data normality and based on that the Mann-Whitney test or unpaired Student t test was applied. The logistic regression analysis was performed with an estimate of its coefficient. For regression, it was estimated the confidence interval of 95% and significance level of 5%. In this analysis was utilized the STATA® software version 14.0. Results: In the evaluation of 36 patients, it was found that survival was lower among the individuals who had the lower percentage of caloric adequacy (p=0,010) and protein (p=<0,001). It was observed that the protein supply impacted expressively the clinical outcome with an increase of 1% in the average protein adequacy, the chances of death decreased by 21%. Conclusion: The lower percentage of caloric-protein adequacy was associated with lower mortality of critical patients. In addition, in this sampling, it was observed that the protein adequacy percentual joined expressively in the clinical outcome

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Water scarcity and excess adiposity are two of the main problems worldwide and in Mexico, which is the most obese country in the world and suffers from water scarcity. Food production represents 90% of a person's water footprint (WF), and healthy diets can lead to less WF than do unhealthy diets related to obesity. We calculated the WF of the diet and caloric intake of adults in Mexico and analyzed its relationship with adiposity. Also, the risk of water expenditure due to adiposity and adherence to dietary recommendations regarding WF of international healthy diets were examined. A Food Consumption Frequency Questionnaire (FCFQ) was applied to 395 adults. Body mass index (BMI), associated with adiposity indicators, was used as a reference for grouping a sample into adiposity levels. The WF was calculated according to the WF Assessment Method, considering correction factors and accounting for water involved in cooking and food washing. Our results showed that the Mexican diet spends 6,056 liters per person per day (L p-1d-1) and is 55% higher than international healthy diets WF. Consumption of beef, milk, fruits, chicken, and fatty cereals represented 56% of total WF. Strong relations appeared between hypercaloric diets and high WF. Diets of people with excess adiposity generated statistically higher WF with extra expenses of 729 L p-1d-1 compared with the normal adiposity population. Following nutritional recommendations offers a protective factor in water care, whereas not adhering to these represents a risk up to 93 times greater of water expenditure regarding international healthy diets. Therefore, both for the general population and to regulate obesity, adequate diets can help mitigate the problem of water scarcity.

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Access, nutritional characteristics, preferences, and cost can affect food intake at school. A cross-sectional study was performed to determine the nutritional characteristics, sites of origin, and cost of foods consumed during school hours. Three hundred and sixty-nine children from five public elementary schools in Mexico City participated. The children gave information about the foods that they consumed five days out of the week during school hours, including the place of acquisition, cost of the food, and portion size. Anthropometric measurements of height and weight of the children were taken. Caloric consumption and percentage of recommended daily energy intake from food during school hours was determined. Children were 10.9 ± 0.9 years old; 55.6% were girls, 26% were overweight, 23% were obese, and 3.3% were of low height for age. The average calorie intake was 515 kilocalories (kcal) (boys, 535 kcal; girls, 476 kcal, p = 0.051); calorie intake was higher when school meal intakes included foods from home, school, and outside of school. No significant differences were found in calorie intake by children's nutritional status. The cost in Mexican pesos per 100 kcal consumed showed differences according to the nutritional status of the children; it was 4.0 Mexican pesos for children with normal weight and 4.2 and 3.8 pesos in children who were overweight or obese, respectively. The information obtained in this study should be used to provide nutritional guidance. The food portion size intake during school hours should be reduced, and the food should come from one or at most two sites, because each extra food represents an increase in the total kilocalorie intake.

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PURPOSE: Our main objective was to use the Maximum Acute Gastrointestinal Injury Score (AGImax) to evaluate the prognostic capability of gastrointestinal dysfunction (GID), on hospital mortality in patients on mechanical ventilation (MV) requiring vasopressors. A secondary goal was to analyze the relationship between AGImax and vasopressor dosage with increasing caloric intake. MATERIALS AND METHODS: Prospective multicenter cohort study in ten ICUs across Argentina. Consecutive adult patients on MV, requiring vasopressors and receiving enteral nutrition (EN) were included. AGImax was identified (I-IV) using a modified AGI score. Comparisons of clinical and outcome variables were performed in 3 predetermined EN-groups: <10 kcal/kg/d, ≥10 to <20 kcal/kg/d, or ≥ 20 kcal/kg/d. RESULTS: A total of 494 patients met all inclusion criteria. Forty-four percent of patients had severe AGImax and 17% received <10 kcal/kg/day, indicating more severity and higher mortality. Notable independent predictors of mortality were AGImax, vasopressors, and caloric intake. PN was the only factor which had an inverse relationship to mortality. CONCLUSIONS: In this population, patients with AGImax III-IV were significantly associated with lower caloric intake and greater hospital mortality, highlighting the importance of AGI as a prognostic tool. As PN was linked with lower mortality, it could be an option to explore in further studies.

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