Fibroblast growth factor 21 is a hepatokine involved in MASLD progression.

AIM: We aimed to assess the role of FGF21 in metabolic dysfunction-associated steatotic liver disease (MASLD) at a multi-scale level. METHODS: We used human MASLD pathology samples for FGF21 gene expression analyses (qPCR and RNAseq), serum to measure circulating FGF21 levels and DNA for genotyping the FGF21 rs838133 variant in both estimation and validation cohorts. A hepatocyte-derived cell line was exposed to free fatty acids at different timepoints. Finally, C57BL/6J mice were fed a high-fat and choline-deficient diet (CDA-HFD) for 16 weeks to assess hepatic FGF21 protein expression and FGF21 levels by ELISA. RESULTS: A significant upregulation in FGF21 mRNA expression was observed in the liver analysed by both qPCR (fold change 5.32 ± 5.25 vs. 0.59 ± 0.66; p = 0.017) and RNA-Seq (3.5 fold; FDR: 0.006; p < 0.0001) in MASLD patients vs. controls. Circulating levels of FGF21 were increased in patients with steatohepatitis vs. bland steatosis (386.6 ± 328.9 vs. 297.9 ± 231.5 pg/mL; p = 0.009). Besides, sex, age, A-allele from FGF21, GG genotype from PNPLA3, ALT, type 2 diabetes mellitus and BMI were independently associated with MASH and significant fibrosis in both estimation and validation cohorts. In vitro exposure of Huh7.5 cells to high concentrations of free fatty acids (FFAs) resulted in overexpression of FGF21 (p < 0.001). Finally, Circulating FGF21 levels and hepatic FGF21 expression were found to be significantly increased (p < 0.001) in animals under CDA-HFD. CONCLUSIONS: Hepatic and circulating FGF21 expression was increased in MASH patients, in Huh7.5 cells under FFAs and in CDA-HFD animals. The A-allele from the rs838133 variant was also associated with an increased risk of steatohepatitis and significant and advanced fibrosis in MASLD patients.

Preventing Mislabeling: A Comparative Chromatographic Analysis for Classifying Medical and Industrial Cannabis.

Gas chromatography (GC) techniques for analyzing and determining the cannabinoid profile in cannabis (Cannabis sativa L.) are widely used in standard laboratories; however, these methods may mislabel the profile when used under rapid conditions. Our study aimed to highlight this problem and optimize GC column conditions and mass spectrometry (MS) parameters to accurately identify cannabinoids in both standards and forensic samples. The method was validated for linearity, selectivity, and precision. It was observed that when tetrahydrocannabinol (Δ9-THC) and cannabidiolic acid (CBD-A) were examined using rapid GC conditions, the resulting derivatives generated identical retention times. Wider chromatographic conditions were applied. The linear range for each compound ranged from 0.02 µg/mL to 37.50 µg/mL. The R2 values ranged from 0.996 to 0.999. The LOQ values ranged from 0.33 µg/mL to 5.83 µg/mL, and the LOD values ranged from 0.11 µg/mL to 1.92 µg/mL. The precision values ranged from 0.20% to 8.10% RSD. In addition, forensic samples were analyzed using liquid chromatography (HPLC-DAD) in an interlaboratory comparison test, with higher CBD and THC content than GC-MS determination (p < 0.05) in samples. Overall, this study highlights the importance of optimizing GC techniques to avoid mislabeling cannabinoids in cannabis samples.

Overtraining Syndrome: one more piece of the Central Sensitivity Syndrome puzzle / Síndrome de Sobreentrenamiento: una pieza más del puzle del Síndrome de Sensibilidad Central / Síndrome do supertreinamento: mais uma peça do enigma da Síndrome de Sensibilização Central

The initial focus of overtraining syndrome was physical overexertion with inadequate rest, causing severe chronic fatigue and decreased performance. The pathophysiological knowledge has subsequently evolved, and although the exact mechanisms of overtraining syndrome are unknown, several hypotheses arise. The most prominent of these are: the existence of an immunoneuroendocrine imbalance and dysfunction of the central nervous system and of the neuroendocrine axis. On the other hand, central sensitivity syndrome encompasses nosological entities that share the pathophysiological mechanisms that cause them, that is, an immunoneuroendocrine and mitochondrial dysfunction as well as an oxidative stress imbalance. The most common entities within central sensitivity syndrome are fibromyalgia, tension headache and/or migraine, chronic fatigue syndrome, irritable bowel syndrome, multiple chemical syndrome, electrosensitivity syndrome, irritable bladder syndrome, and restless leg syndrome, among others. The pathophysiological and clinical analogy between overtraining syndrome and central sensitivity syndrome raises the possibility of including overtraining syndrome within central sensitivity syndrome, since a stressful stimulus such as chronic overtraining coupled with unbalanced compensatory systems can generate, at a given time, immunoneuroendocrine sensitization and therefore central sensitivity syndrome

El enfoque inicial del síndrome de sobreentrenamiento ha sido el sobreesfuerzo físico con un descanso no adecuado, que provocaba fatiga crónica severa y disminución en el rendimiento. Posteriormente ha ido evolucionando el conocimiento fisiopatológico, y aunque se desconocen los mecanismos fisiopatológicos exactos del síndrome de sobreentrenamiento, se plantean diversas hipótesis. Las más destacadas son: la existencia de un desbalance inmunoneuroendocrino y disfunción del sistema nervioso central y el eje neuroendocrino. Por su parte el síndrome de sensibilidad central engloba entidades nosológicas que tienen en común las razones fisiopatológicas que las ocasionan, esto es, una disfunción inmunoneuroendocrina, mitocondrial y un desbalance del estrés oxidativo. Las entidades más comunes dentro del síndrome de sensibilidad central suelen ser la fibromialgia, la cefalea tensional y/o migraña, el síndrome de fatiga crónica, el síndrome de intestino irritable, el síndrome químico múltiple, el síndrome de electrosensibilidad, el síndrome de la vejiga irritable, el síndrome de piernas inquietas, entre otros. La analogía fisiopatológica y clínica entre el síndrome de sobreentrenamiento y el síndrome de sensibilidad central, plantea la posibilidad de englobar al síndrome de sobreentrenamiento dentro del síndrome de sensibilidad central, ya que ante la presencia de un estímulo estresante como lo es el sobreentrenamiento crónico, unido a sistemas compensadores desequilibrados, puede generar en un momento determinado una sensibilización

O foco inicial da síndrome do supertreinamento foi o excesso de esforço físico com descanso inadequado, causando fadiga crônica grave e diminuição do desempenho. Posteriormente o conhecimento fisiopatológico evoluiu e, embora os mecanismos exatos da síndrome do supertreinamento sejam desconhecidos, surgem várias hipóteses. Os mais proeminentes são: a existência de um desequilíbrio imunoneuroendócrino e disfunção do sistema nervoso central e do eixo neuroendócrino. Por outro lado, a síndrome da sensibilização central engloba entidades nosológicas que compartilham os mecanismos fisiopatológicos que as causam, ou seja, uma disfunção imunoneuroendócrina e mitocondrial, bem como um desequilíbrio de estresse oxidativo. As entidades mais comuns dentro da síndrome da sensibilização central são fibromialgia, cefaleia e/ou enxaqueca, síndrome de fadiga crônica, síndrome do intestino irritável, síndrome química múltipla, síndrome de eletrosensibilidade, síndrome da bexiga irritável e síndrome das pernas inquietas, entre outros. A analogia fisiopatológica e clínica entre síndrome do supertreinamento e síndrome da sensibilização central levanta a possibilidade de incluir a síndrome do supertreinamento dentro da síndrome da sensibilização central, uma vez que um estímulo estressante, como o supertreinamento crônico, juntamente com sistemas compensatórios desequilibrados, pode gerar, em determinado momento, sensibilização imunoneuroendócrina e, portanto, síndrome da sensibilização central

Dissecting the Brain/Islet Axis in Metabesity.

The high prevalence of type 2 diabetes mellitus (T2DM), together with the fact that current treatments are only palliative and do not avoid major secondary complications, reveals the need for novel approaches to treat the cause of this disease. Efforts are currently underway to identify therapeutic targets implicated in either the regeneration or re-differentiation of a functional pancreatic islet ß-cell mass to restore insulin levels and normoglycemia. However, T2DM is not only caused by failures in ß-cells but also by dysfunctions in the central nervous system (CNS), especially in the hypothalamus and brainstem. Herein, we review the physiological contribution of hypothalamic neuronal and glial populations, particularly astrocytes, in the control of the systemic response that regulates blood glucose levels. The glucosensing capacity of hypothalamic astrocytes, together with their regulation by metabolic hormones, highlights the relevance of these cells in the control of glucose homeostasis. Moreover, the critical role of astrocytes in the response to inflammation, a process associated with obesity and T2DM, further emphasizes the importance of these cells as novel targets to stimulate the CNS in response to metabesity (over-nutrition-derived metabolic dysfunctions). We suggest that novel T2DM therapies should aim at stimulating the CNS astrocytic response, as well as recovering the functional pancreatic ß-cell mass. Whether or not a common factor expressed in both cell types can be feasibly targeted is also discussed.

NUTRITIONAL INTAKE AND NUTRITIONAL STATUS IN ELITE MEXICAN TEENAGERS SOCCER PLAYERS OF DIFFERENT AGES.

INTRODUCTION: nutritional intake and status of soccer players has attracted not much research attention. Many soccer players follow an inadequate nutritional intake and have a poor nutritional status. This is relevant in youngsters soccer players, in order to improve performance and promote healthy dietary practices. AIMS: analyze anthropometric characterizes, evaluate nutritional intake and status, dietary habits and pre- and post-exercise meals in elite teenagers soccer players. METHODS: seventy-two young male soccer players (15-20 years) from four junior teams of a soccer Club from the Mexican National Soccer League were measured for height, seat height, weight, 6 skinfolds, 6 diameters and 7 circumferences, height-for-age and BMI-for-age values. Skin, adipose, muscle, bone and residual tissue masses were calculated with the Ross and Kerr equation. Resting energy expenditure and intake was also measured. Daily dietary intake was self-recorded for 4 consecutive days (excluding the match day) using a digital food-weighing scale and a food record questionnaire. Dietary analysis was performed using the NutriBase 7 Clinical software. Several biochemical values were determined. One-way analysis of variance (ANOVA) and post hoc testing was performed using t-tests with a Bonferroni correction. RESULTS: all soccer players were within the normal range values for anthropometric parameters studies, when compared with other adolescent elite soccer teams. Values of plasma glucose, urea, creatinine, uric acid, lipid profile and total proteins were within normal range for young adult population, although albumin levels were high. Moreover, 14% and 20% of soccer players presented hyperuricemia and elevated total cholesterol levels respectively. Energy expenditure and intake were within normal range for all teenager elite soccer players. However, two teams shower significant lower intakes than demands. All macronutrient intakes were within recommendations, except protein that was higher. Micronutrient intake exceeded the recommendations for general population. Soccer players had pre- and post-exercise meals with an appropriate range of carbohydrates. Food intake was mainly based on cereals, derivatives and potatoes; meat, poultry, fish, shellfish and eggs and biscuits and confectionery and poor in fruit, vegetables and milk and dairy products. CONCLUSIONS: the population of soccer players did not have optimal nutritional habits. However, their nutritional intake and status was better than in other published studies. The main problems of these teams were that they had a high protein diet and that in some teams the nutritional intake was not enough to cover the demands. Finally, nutritional intake was found to be of poor quality. Thus, we recommend nutritional education for soccer players of these teams.

Introducción: la ingesta nutricional y el estado nutricional de los futbolistas no han suscitado mucha atención. La mayoría de los futbolistas siguen una dieta inadecuada y tienen una condición nutricional pobre. Esto adquiere mayor importancia cuando se trata de jugadores jóvenes, ya que se podrían mejorar su juego y sus hábitos nutricionales. Objetivos: analizar las características antropométricas, la ingesta y el estado nutricional, los hábitos dietéticos y la alimentación antes y después del ejercicio en equipos de élite de futbolistas adolescentes. Métodos: se estudiaron a 72 jugadores masculinos de 15-20 años, pertenecientes a cuatro equipos junior de un club mejicano de la Liga de Fútbol Nacional. A los jugadores se les midió el peso, la altura, la altura sentado, seis pliegues cutáneos, seis diámetros, siete circunferencias, los valores estatura para la edad e IMC para la edad. La masa de piel, tejido adiposo, músculo, hueso y masa residual se calcularon con la ecuación de Ross y Kerr. Se midió el gasto energético y la ingesta energética diaria. Se recogió la ingesta diaria durante cuatro días (excluyendo el día del partido) y se empleó una báscula digital y un cuestionario dietético. El análisis dietético se realizó con el programa NutriBase 7 Clinical. Se midieron varios parámetros bioquímicos. Se empleó el test ANOVA y los test post hoc usados fueron el de la t´Student y el de Bonferroni. Resultados: los parámetros antropométricos de todos los futbolistas estudiados se encontraban dentro de los valores normales para futbolistas de élite adolescentes. Los valores plasmáticos de glucosa, urea, creatinina, ácido úrico, perfil lipídico y proteínas totales estaban dentro de los valores normales de la población adolescente. Sin embargo, la albúmina se encontraba elevada y el 14 y el 20% de los futbolistas presentaban niveles altos de ácido úrico y colesterol. La ingesta energética y el gasto energético eran los habituales en los futbolistas de élite adolescentes, aunque dos equipos tenían una ingesta energética inferior a sus necesidades. El consumo de micronutrientes era superior a las recomendaciones para la población normal. Los futbolistas ingerían comidas pre y post-ejercicio, con unas cantidades adecuadas de carbohidratos. Su alimentación se basaba fundamentalmente en el consumo de cereales, pastas y derivados; productos cárnicos; pescados; huevos; bollería industrial y golosinas. Además era muy pobre en frutas, verduras y productos lácteos. Conclusiones: la población de futbolistas estudiados no tuvo unos hábitos nutricionales óptimos. Sin embargo, fueron mejores que los que se vieron en otros estudios publicados. Los principales problemas nutricionales observados fueron que la dieta era elevada en proteínas, que en algunos casos era insuficiente para cubrir las demandas energéticas y que era poco variada. Así pues, se recomienda una educación nutricional para esos equipos de futbolistas.

Nutritional intake and nutritional status in elite Mexican teenagers soccer players of different ages / Ingesta nutricional y estado nutricional de jugadores de élite adolescentes, de fútbol mexicano, de diferentes edades

Introduction: nutritional intake and status of soccer players has attracted not much research attention. Many soccer players follow an inadequate nutritional intake and have a poor nutritional status. This is relevant in youngsters soccer players, in order to improve performance and promote healthy dietary practices. Aims: analyze anthropometric characterizes, evaluate nutritional intake and status, dietary habits and pre- and post-exercise meals in elite teenagers soccer players. Methods: seventy-two young male soccer players (15-20 years) from four junior teams of a soccer Club from the Mexican National Soccer League were measured for height, seat height, weight, 6 skinfolds, 6 diameters and 7 circumferences, height-for-age and BMI-for-age values. Skin, adipose, muscle, bone and residual tissue masses were calculated with the Ross and Kerr equation. Resting energy expenditure and intake was also measured. Daily dietary intake was self-recorded for 4 consecutive days (excluding the match day) using a digital food-weighing scale and a food record questionnaire. Dietary analysis was performed using the NutriBase 7 Clinical software. Several biochemical values were determined. One-way analysis of variance (ANOVA) and post hoc testing was performed using t-tests with a Bonferroni correction. Results: all soccer players were within the normal range values for anthropometric parameters studies, when compared with other adolescent elite soccer teams. Values of plasma glucose, urea, creatinine, uric acid, lipid profile and total proteins were within normal range for young adult population, although albumin levels were high. Moreover, 14% and 20% of soccer players presented hyperuricemia and elevated total cholesterol levels respectively. Energy expenditure and intake were within normal range for all teenager elite soccer players. However, two teams shower significant lower intakes than demands. All macronutrient intakes were within recommendations, except protein that was higher. Micronutrient intake exceeded the recommendations for general population. Soccer players had pre- and post-exercise meals with an appropriate range of carbohydrates. Food intake was mainly based on cereals, derivatives and potatoes; meat, poultry, fish, shellfish and eggs and biscuits and confectionery and poor in fruit, vegetables and milk and dairy products. Conclusions: the population of soccer players did not have optimal nutritional habits. However, their nutritional intake and status was better than in other published studies. The main problems of these teams were that they had a high protein diet and that in some teams the nutritional intake was not enough to cover the demands. Finally, nutritional intake was found to be of poor quality. Thus, we recommend nutritional education for soccer players of these teams (AU)

Introducción: la ingesta nutricional y el estado nutricional de los futbolistas no han suscitado mucha atención. La mayoría de los futbolistas siguen una dieta inadecuada y tienen una condición nutricional pobre. Esto adquiere mayor importancia cuando se trata de jugadores jóvenes, ya que se podrían mejorar su juego y sus hábitos nutricionales. Objetivos: analizar las características antropométricas, la ingesta y el estado nutricional, los hábitos dietéticos y la alimentación antes y después del ejercicio en equipos de élite de futbolistas adolescentes. Métodos: se estudiaron a 72 jugadores masculinos de 15-20 años, pertenecientes a cuatro equipos junior de un club mejicano de la Liga de Fútbol Nacional. A los jugadores se les midió el peso, la altura, la altura sentado, seis pliegues cutáneos, seis diámetros, siete circunferencias, los valores estatura para la edad e IMC para la edad. La masa de piel, tejido adiposo, músculo, hueso y masa residual se calcularon con la ecuación de Ross y Kerr. Se midió el gasto energético y la ingesta energética diaria. Se recogió la ingesta diaria durante cuatro días (excluyendo el día del partido) y se empleó una báscula digital y un cuestionario dietético. El análisis dietético se realizó con el programa NutriBase 7 Clinical. Se midieron varios parámetros bioquímicos. Se empleó el test ANOVA y los test post hoc usados fueron el de la t´Student y el de Bonferroni. Resultados: los parámetros antropométricos de todos los futbolistas estudiados se encontraban dentro de los valores normales para futbolistas de élite adolescentes. Los valores plasmáticos de glucosa, urea, creatinina, ácido úrico, perfil lipídico y proteínas totales estaban dentro de los valores normales de la población adolescente. Sin embargo, la albúmina se encontraba elevada y el 14 y el 20% de los futbolistas presentaban niveles altos de ácido úrico y colesterol. La ingesta energética y el gasto energético eran los habituales en los futbolistas de élite adolescentes, aunque dos equipos tenían una ingesta energética inferior a sus necesidades. El consumo de micronutrientes era superior a las recomendaciones para la población normal. Los futbolistas ingerían comidas pre y post-ejercicio, con unas cantidades adecuadas de carbohidratos. Su alimentación se basaba fundamentalmente en el consumo de cereales, pastas y derivados; productos cárnicos; pescados; huevos; bollería industrial y golosinas. Además era muy pobre en frutas, verduras y productos lácteos. Conclusiones: la población de futbolistas estudiados no tuvo unos hábitos nutricionales óptimos. Sin embargo, fueron mejores que los que se vieron en otros estudios publicados. Los principales problemas nutricionales observados fueron que la dieta era elevada en proteínas, que en algunos casos era insuficiente para cubrir las demandas energéticas y que era poco variada. Así pues, se recomienda una educación nutricional para esos equipos de futbolistas (AU)