Transgender health objectives of training for adult Endocrinology and Metabolism programs: Outcomes of a modified-Delphi study.

BACKGROUND: Transgender people encounter significant barriers when seeking timely, high-quality healthcare, resulting in unmet medical needs with increased rates of diabetes, asthma, chronic obstructive pulmonary disease, and HIV. The paucity of postgraduate medical education to invest in standardization of transgender health training sustains these barriers, leaving physicians feeling unprepared and averse to provide transgender health care. Closing this education gap and improving transgender healthcare necessitates the development of consensus-built transgender health objectives of training (THOOT), particularly in Adult Endocrinology and Metabolism Residency programs. METHODS: We conducted a two-round modified-Delphi process involving a nationally representative panel of experts, including Adult Endocrinology and Metabolism program directors, physician content experts, residents, and transgender community members, to identify THOOT for inclusion in Canadian Endocrinology and Metabolism Residency programs. Participants used a 5-point Likert scale to assess THOOT importance for curricular inclusion, with opportunities for written feedback. Data was collected through Qualtrics and analyzed after each round. FINDINGS: In the first Delphi round, panelists reviewed and rated 81 literature extracted THOOT, achieving consensus on all objectives. Following panelists' feedback, 5 THOOT were added, 9 removed, 34 consolidated into 12 objectives, and 47 were rephrased or retained. In the second Delphi round, panelists assessed 55 THOOT. Consensus was established for 8 THOOT. Program directors' post-Delphi feedback further consolidated objectives to arrive at 4 THOOT for curriculum inclusion. CONCLUSIONS: To our knowledge, this is the first time a consensus-based approach has been used to establish THOOT for any subspecialty postgraduate medicine program across Canada or the United States. Our results lay the foundation towards health equity and social justice in transgender health medical education, offering a blueprint for future innovations.

Tumor metabolic crosstalk and immunotherapy / Diafonía metabólica tumoral e inmunoterapia

Tumor cells must resist the host's immune system while maintaining growth under harsh conditions of acidity and hypoxia, which indicates that tumors are more robust than normal tissue. Immunotherapeutic agents have little effect on solid tumors, mostly because of the tumor density and the difficulty of penetrating deeply into the tissue to achieve the theoretical therapeutic effect. Various therapeutic strategies targeting the tumor microenvironment (TME) have been developed. Immunometabolic disorders play a dominant role in treatment resistance at both the TME and host levels. Understanding immunometabolic factors and their treatment potential may be a way forward for tumor immunotherapy. Here, we summarize the metabolism of substances that affect tumor progression, the crosstalk between the TME and immunosuppression, and some potential tumor-site targets. We also summarize the progress and challenges of tumor immunotherapy.(AU)

Herramientas para un ajuste de dosis de tacrolimus más personalizado en el seguimiento de los pacientes con transplante renal. Fenotipo metabolizador según polimorfismos genéticos del CYP3A vs. el cociente concentración-dosis / Tools for a personalized tacrolimus dose adjustment in the follow-up of renal transplant recipients: Metabolizing phenotype according to CYP3A genetic polymorphisms versus concentration–dose ratio

Antecedentes y justificación: La estrategia de la aproximación concentración-dosis (C/D) y los distintos perfiles del tacrolimus (Tac), según los polimorfismos del citocromo P450 (CYPs) se centran en el metabolismo de Tac y se plantean como herramientas para el seguimiento de los pacientes trasplantados. El objetivo de este estudio es comparar la exposición al Tac analizado según ambas estrategias. Materiales y métodos: Se han incluido 425 pacientes trasplantados renales. El cálculo del cociente concentración Tac/dosis (C/D) permitió dividir la población en terciles y clasificar los pacientes según su tasa de metabolismo del Tac en tres grupos (rápida, intermedia y lenta). Con base en los polimorfismos del CYP3A4 y A5, los pacientes se agruparon en metabolizadores rápidos (portadores del CYP3A5*1 y CYP34A *1/*1), intermedios (CYP3A5*3/3 y CYP3A4*1/*1) y lentos (CYP3A5 *3/*3 y portadores del CYP3A4*22). Resultados: Al comparar los pacientes de cada grupo metabolizador según los dos criterios, coincidieron 47% (65/139) de los metabolizadores rápidos, 85% (125/146) de los intermedios y solo 12% (17/140) de los lentos. Se observaron concentraciones de Tac estadísticamente menores en los metabolizadores rápidos y concentraciones mayores en los lentos, comparándolos con el grupo intermedio según el cociente C/D o según polimorfismos. Los metabolizadores rápidos requirieron alrededor de 60% más de dosis de Tac que los intermedios a lo largo del seguimiento, mientras que los lentos aproximadamente 20% menos de dosis que los intermedios. Los metabolizadores rápidos clasificados por ambos criterios presentan un porcentaje mayor de veces con valores de concentración de Tac en sangre infraterapéuticos... (AU)

Background and justification: The strategy of the concentration–dose (C/D) approach and the different profiles of tacrolimus (Tac) according to the cytochrome P450 polymorphisms (CYPs) focus on the metabolism of Tac and are proposed as tools for the follow-up of transplant patients. The objective of this study is to analyse both strategies to confirm whether the stratification of patients according to the pharmacokinetic behaviour of C/D corresponds to the classification according to their CYP3A4/5 cluster metabolizer profile. Materials and methods: Four hundred and twenty-five kidney transplant patients who received Tac as immunosuppressive treatment have been included. The concentration/dose ratio (C/D) was used to divided patients in terciles and classify them according to their Tac metabolism rate (fast, intermediate, and slow). Based on CYP3A4 and A5 polymorphisms, patients were classified into three metabolizer groups: fast (CYP3A5*1 and CYP34A*1/*1 carriers), intermediate (CYP3A5*3/3 and CYP3A4*1/*1) and slow (CYP3A5*3/*3 and CYP3A4*22 carriers). Results: When comparing patients included in each metabolizer group according to C/D ratio, 47% (65/139) of the fast metabolizers, 85% (125/146) of the intermediate and only 12% (17/140) of the slow also fitted in the homonym genotype group. Statistically lower Tac concentrations were observed in the fast metabolizers group and higher Tac concentrations in the slow metabolizers when compared with the intermediate group both in C/D ratio and polymorphisms criteria. High metabolizers required approximately 60% more Tac doses than intermediates throughout follow-up, while poor metabolizers required approximately 20% fewer doses than intermediates. Fast metabolizers classified by both criteria presented a higher percentage of times with sub-therapeutic blood Tac concentration values... (AU)

Investigating the impact of high-intensity interval training and crossover point training on blood lipid metabolism in overweight female college students

Background and purpose of the study: There is a significant correlation between the level of lipid metabolism markers in serum and the incidence of cardiovascular and metabolic diseases, based on which, maintaining the health of lipid metabolism is of great significance in improving the quality of life and preventing the occurrence of diseases. At the same time, with the gradual improvement of living standards and economic level, people's demand for health is also increasing, so there is an urgent need to find ways to exercise to maximize the health benefits within a limited period of time. Study subjects and methods:A total of 30 female college students with BIM test results ≥24kg/m2 and <27.9kg/m2 were selected for this study.The 30 female college students were randomly divided into three groups, which were labeled as the control group (SSC group), the high-intensity interval training group (HIIT group), and the cross-point training group (COP group) in accordance with the differences in the implementation of the research methods.Prior to the implementation of the exercise intervention, a maximal oxygen uptake test and a crossover point test were completed to pinpoint the acceptable exercise intensity for each individual.A 10-week exercise intervention program was implemented 3 times per week for 10 weeks for female students in the HIIT and COP groups to ensure that the daily physical activity of female students in the SSC group remained unchanged. In the HIIT group, the female students were required to complete 5 sets of high-intensity interval training for a total of 35 minutes per session, with each set consisting of 4 minutes of running (at 85% of maximal oxygen uptake) interspersed with 3 minutes of walking (at 50% of maximal oxygen uptake)...(AU)

Fármacos antipsicóticos de segunda generación y su impacto en el tejido adiposo / Second-generation antipsychotic drugs and their impact on adipose tissue

La esquizofrenia es un trastorno neuropsiquiátrico crónico que afecta a 21 millones de personas en todo el mundo. Actualmente, los fármacos antipsicóticos de segunda generación o atípicos (FASG) son los medicamentos de elección para el tratamiento de esta enfermedad. Sin embargo, a pesar de su alta eficacia en contrarrestar la sintomatología neuropsiquiátrica de la esquizofrenia, observaciones clínicas recientes en pacientes tratados con FASG evidencian un aumento en la prevalencia de diferentes alteraciones metabólicas, entre las que se incluyen el aumento de peso corporal, la hiperglucemia y la dislipidemia. A pesar de que no se conocen en detalle los mecanismos moleculares responsables de estos efectos secundarios, cada vez más investigaciones apuntan a una relación entre los tratamientos con FASG y las alteraciones en los diferentes depósitos de tejido adiposo blanco, marrón y beige. En esta revisión analizamos el conocimiento actual en esta área destacando aspectos moleculares de la biología de los adipocitos, entre los que se encuentran los procesos de diferenciación, metabolismo lipídico, función termogénica y el proceso de pardeamiento o beiging.(AU)

Schizophrenia is a chronic neuropsychiatric disorder that affects 21 million people worldwide. Currently, second-generation or atypical antipsychotics (SGAs) are the first-line medications for the treatment of this disease. However, despite its high efficacy in counteracting the neuropsychiatric symptoms of schizophrenia, recent clinical investigations in patients treated with SGAs show an increase in the prevalence of pivotal metabolic alterations, including increased body weight, hyperglycemia and dyslipidemia. Although the molecular mechanisms responsible for these side effects are not fully understood, cumulative evidences associate SGA administration with alterations in the different adipose tissue depots of white, brown and beige adipocytes. In this review, we have recapitulated the current knowledge in this area with a particular focus on the molecular aspects of the adipocyte biology, including differentiation, lipid metabolism, thermogenic function and browning processes.(AU)

Parkin depletion prevents the age-related alterations in the FGF21 system and the decline in white adipose tissue thermogenic function in mice

Parkin is an ubiquitin‐E3 ligase that is involved in cellular mitophagy and was recently shown to contribute to controlling adipose tissue thermogenic plasticity. We found that Parkin expression is induced in brown (BAT) and white (WAT) adipose tissues of aged mice. We determined the potential role of Parkin in the aging-associated decline in the thermogenic capacity of adipose tissues by analyzing subcutaneous WAT, interscapular BAT, and systemic metabolic and physiological parameters in young (5 month-old) and aged (16 month-old) mice with targeted invalidation of the Parkin (Park2) gene, and their wild-type littermates. Our data indicate that suppression of Parkin prevented adipose accretion, increased energy expenditure and improved the systemic metabolic derangements, such as insulin resistance, seen in aged mice. This was associated with maintenance of browning and reduction of the age-associated induction of inflammation in subcutaneous WAT. BAT in aged mice was much less affected by Parkin gene invalidation. Such protection was associated with a dramatic prevention of the age-associated induction of fibroblast growth factor-21 (FGF21) levels in aged Parkin-invalidated mice. This was associated with a parallel reduction in FGF21 gene expression in adipose tissues and liver in aged Parkin-invalidated mice. Additionally, Parkin invalidation prevented the protein down-regulation of β-Klotho (a key co-receptor mediating FGF21 responsiveness in tissues) in aged adipose tissues. We conclude that Parkin down-regulation leads to improved systemic metabolism in aged mice, in association with maintenance of adipose tissue browning and FGF21 system functionality. (AU)

Effects of resistance training on heat shock response (HSR), HSP70 expression, oxidative stress, inflammation, and metabolism in middle-aged people

Resistance training (RT) can increase the heat shock response (HSR) in the elderly. As middle-aged subjects already suffer physiological declines related to aging, it is hypothesized that RT may increase the HSR in these people. To assess the effects of resistance training on heat shock response, intra and extracellular HSP70, oxidative stress, inflammation, body composition, and metabolism in middle-aged subjects. Sixteen volunteers (40 – 59 years) were allocated to two groups: the trained group (n = 7), which performed 12 weeks of RT; and the physically inactive—control group (n = 9), which did not perform any type of exercise. The RT program consisted of 9 whole-body exercises (using standard gym equipment) and functional exercises, carried out 3 times/week. Before and after the intervention, body composition, muscle mass, strength, functional capacity, and blood sample measurements (lipid profile, glucose, insulin, oxidative damage, TNF-α, the HSR, HSP70 expression in leukocytes, and HSP72 in plasma) were performed. The HSR analysis demonstrated that this response is maintained at normal levels in middle-aged people and that RT did not cause any improvement. Also, RT increases muscle mass, strength, and functional capacity. Despite no additional changes of RT on the antioxidant defenses (catalase, glutathione peroxidase, and reductase) or inflammation, lipid peroxidation was diminished by RT (group x time interaction, p = 0.009), indicating that other antioxidant defenses may be improved after RT. HSR is preserved in middle-aged subjects without metabolic complications. In addition, RT reduces lipid peroxidation and can retard muscle mass and strength loss related to the aging process. (AU)

Imbalanced metabolism induced NH4+ accumulation and its effect on the central metabolism of Methylomonas sp. ZR1 / El metabolismo desequilibrado indujo la acumulación de NH4+ y su efecto sobre el metabolismo central de Methylomonas sp. ZR1

Nitrogen and carbon are the two most essential nutrient elements, and their metabolism is tightly coupled in single carbon metabolic microorganisms. However, the nitrogen metabolism and the nitrogen/carbon (N/C) metabolic balance in single-carbon metabolism is poorly studied. In this study, the nitrogen metabolism pattern of the fast growing methanotrophs Methylomonas sp. ZR1 grown in methane and methanol was studied. Effect study of different nitrogen sources on the cell growth of ZR1 indicates that nitrate salts are the best nitrogen source supporting the growth of ZR1 using methane and methanol as carbon source. However, its metabolic intermediate ammonium was found to accumulate with high N/C ratio in the medium and consequently inhibit the growth of ZR1. Studies of carbon and nitrogen metabolic kinetic under different N/C ratio conditions indicate that the accumulation of NH4+ is caused by the imbalanced nitrogen and carbon metabolism in ZR1. Feeding carbon skeleton α-ketoglutaric acid could effectively relieve the inhibition effect of NH4+ on the growth of ZR1, which further confirms this assumption. qPCR analysis of the expression level of the central metabolic key enzyme gene indicates that the nitrogen metabolic intermediate ammonium has strong regulation effect on the central nitrogen and carbon metabolism in ZR1. qPCR-combined genomic analysis confirms that a third ammonium assimilation pathway glycine synthesis system is operated in ZR1 to balance the nitrogen and carbon metabolism. Based on the qPCR result, it was also found that ZR1 employs two strategies to relieve ammonium stress in the presence of ammonium: assimilating excess ammonium or cutting off the nitrogen reduction reactions according to the available C1 substrate. Validating the connections between single-carbon and nitrogen metabolism and studying the accumulation and assimilation mechanism of ammonium will contribute to understand how nitrogen regulates cellular growth in single-carbon metabolic microorganisms.(AU)

Parkin depletion prevents the age-related alterations in the FGF21 system and the decline in white adipose tissue thermogenic function in mice

Parkin is an ubiquitin‐E3 ligase that is involved in cellular mitophagy and was recently shown to contribute to controlling adipose tissue thermogenic plasticity. We found that Parkin expression is induced in brown (BAT) and white (WAT) adipose tissues of aged mice. We determined the potential role of Parkin in the aging-associated decline in the thermogenic capacity of adipose tissues by analyzing subcutaneous WAT, interscapular BAT, and systemic metabolic and physiological parameters in young (5 month-old) and aged (16 month-old) mice with targeted invalidation of the Parkin (Park2) gene, and their wild-type littermates. Our data indicate that suppression of Parkin prevented adipose accretion, increased energy expenditure and improved the systemic metabolic derangements, such as insulin resistance, seen in aged mice. This was associated with maintenance of browning and reduction of the age-associated induction of inflammation in subcutaneous WAT. BAT in aged mice was much less affected by Parkin gene invalidation. Such protection was associated with a dramatic prevention of the age-associated induction of fibroblast growth factor-21 (FGF21) levels in aged Parkin-invalidated mice. This was associated with a parallel reduction in FGF21 gene expression in adipose tissues and liver in aged Parkin-invalidated mice. Additionally, Parkin invalidation prevented the protein down-regulation of β-Klotho (a key co-receptor mediating FGF21 responsiveness in tissues) in aged adipose tissues. We conclude that Parkin down-regulation leads to improved systemic metabolism in aged mice, in association with maintenance of adipose tissue browning and FGF21 system functionality. (AU)

Effects of resistance training on heat shock response (HSR), HSP70 expression, oxidative stress, inflammation, and metabolism in middle-aged people

Resistance training (RT) can increase the heat shock response (HSR) in the elderly. As middle-aged subjects already suffer physiological declines related to aging, it is hypothesized that RT may increase the HSR in these people. To assess the effects of resistance training on heat shock response, intra and extracellular HSP70, oxidative stress, inflammation, body composition, and metabolism in middle-aged subjects. Sixteen volunteers (40 – 59 years) were allocated to two groups: the trained group (n = 7), which performed 12 weeks of RT; and the physically inactive—control group (n = 9), which did not perform any type of exercise. The RT program consisted of 9 whole-body exercises (using standard gym equipment) and functional exercises, carried out 3 times/week. Before and after the intervention, body composition, muscle mass, strength, functional capacity, and blood sample measurements (lipid profile, glucose, insulin, oxidative damage, TNF-α, the HSR, HSP70 expression in leukocytes, and HSP72 in plasma) were performed. The HSR analysis demonstrated that this response is maintained at normal levels in middle-aged people and that RT did not cause any improvement. Also, RT increases muscle mass, strength, and functional capacity. Despite no additional changes of RT on the antioxidant defenses (catalase, glutathione peroxidase, and reductase) or inflammation, lipid peroxidation was diminished by RT (group x time interaction, p = 0.009), indicating that other antioxidant defenses may be improved after RT. HSR is preserved in middle-aged subjects without metabolic complications. In addition, RT reduces lipid peroxidation and can retard muscle mass and strength loss related to the aging process. (AU)

Genética y genómica de la longevidad y el envejecimiento / Genetics and genomics of longevity and aging

El envejecimiento y la longevidad son procesos que involucran una serie de factores genéticos, bioquímicos y ambientales. En esta revisión se tratan algunas cuestiones sobre estos dos procesos biológicos y epigenéticos. Se presentan los genes más importantes en estos procesos, así como se ejemplifican enfermedades que presentan un aceleramiento o falla en la longevidad y el envejecimiento. Se usa el análisis inteligente de datos para hallar interacciones de proteínas/genes que expliquen estos dos fenómenos biológicos.

Aging and longevity are processes that involve a series of genetic, biochemical and environmental factors. This review addresses some issues about these two biological and epigenetic processes. The most important genes in these processes are presented, as well as diseases that present an acceleration or failure in longevity and aging. Intelligent data analysis is used to find protein/gene interactions that explain these two biological phenomena.

Characteristics of the metabolically unhealthy phenotype in menopausal resistance training practitioners / Características del fenotipo metabólicamente no saludable en practicantes de entrenamiento deresistencia en la menopausia

Objective: to evaluate clinical, metabolic and body characteristics related to the metabolically unhealthy phenotype (MUH) in menopausal womenwho practice resistance training (RT).Methods: cross-sectional study with a sample of 31 women. Clinical and metabolic variables were measured. Body adiposity was assessedby body mass index, waist circumference, visceral adiposity index (VAI) and lipid accumulation product (LAP). Body composition analysis wasperformed by DEXA.Results: the prevalence of the MH phenotype was 74.2 %. Metabolically healthy (MH) women were younger, had more years of RT practice,higher HDL-c levels and lower VAI and android/gynoid ratio (A/G) than the MUH women. Women with inadequacy of HDL-c, TG, A/G and VAI had12.50 (95 % CI: 3.30-47.23), 4.83 (95 % CI: 2.37-9.85), 5.20 (95 % CI: 1.90-14.16) and 3.12 (95 % CI: 1.07-9.04) times greater prevalenceof the MUH phenotype, respectively, than those with adequacy of these parameters. Binary logistic regression analysis demonstrated that age isa predictor of the MUH phenotype (OR = 1.254; 95 % CI: 1.00-1.56) and this variable showed correlation with TG, VAI and A/G. There was noassociation between thyrotropin and MUH phenotype in the present sample.Conclusion: age and visceral adiposity are predictors for the MUH phenotype in RT practitioners in menopause, which may initially be characterized by alterations in serum lipid profile. (AU)

Objetivo: evaluar las características clínicas, metabólicas y corporales relacionadas con el fenotipo metabólicamente no saludable (MNS) enmujeres menopáusicas que practican entrenamiento de resistencia (ER).Métodos: estudio transversal con 31 mujeres. Se midieron variables clínicas y metabólicas. La adiposidad corporal se evaluó mediante el índicede masa corporal, la circunferencia de la cintura, el índice de adiposidad visceral (IAV) y el producto de acumulación de lípidos (PAL). El análisisde composición corporal fue realizado por DEXA.Resultados: la prevalencia del fenotipo metabólicamente saludable (MS) fue del 74,2 %. Las mujeres metabólicamente saludables (MS) eranmás jóvenes, tenían más años de práctica de ER, niveles más altos de HDL-c y menor IAV y relación androide/ginoide (A/G) que las mujeresMNS. Hubo asociación del fenotipo MNS con los niveles de HDL-c y A/G. Las mujeres con insuficiencia de HDL-c, TG, A/G y IAV tuvieron 12,50(IC 95 %: 3,30-47,23), 4,83 (IC 95 %: 2,37-9,85), 5,20 (IC 95 %: 1,90-14,16) y 3,12 (IC 95 %: 1,07-9,04) veces mayor prevalencia del fenotipoMNS, respectivamente, que aquellas con adecuación de estos parámetros. El análisis de regresión logística binaria demostró que la edad es unpredictor del fenotipo MUH (OR = 1,254; IC 95 %: 1,00-1,56) y esta variable mostró correlación con TG, VAI and A/G. No hubo asociación entrela tirotropina y el fenotipo MUH en la presente muestra.Conclusión: la edad y la adiposidad visceral son predictores del fenotipo MUH en practicantes de ER en la menopausia, que puede caracterizarseinicialmente alteraciones en el perfil plasmático de insípidos. (AU)

Adipocytes-derived exosomal miR-122 promotes non-alcoholic fat liver disease progression via targeting Sirt1 / El miR-122 exosomal derivado de los adipocitos promueve la progresión de la enfermedad hepática por grasa no alcohólica a través de la focalización de Sirt1

Aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects adipose function. This study aimed to explore the function of adipocytes-derived exosomal (ADEs) miR-122 in NAFLD. Methods: A high-fat and high-fructose diet-induced rat model and a palmitic acid (PA)-induced in vitro model were established. The RNA level of miR-122 and Sirt1 was measured using qRT-PCR. The protein levels of exosome biomarkers, and lipogenesis, inflammation and fibrosis biomarkers were determined by western blotting. Cell viability and apoptosis were assessed using cell counting kit-8 and flow cytometry, respectively. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride levels were measured. Liver tissue damage was assessed using haematoxylin and eosin staining. The interaction between miR-122 and Sirt1 3′UTR was assessed using a luciferase reporter gene assay. Results: ADEs exhibited abundant level of miR-122 and promoted lipogenesis, impaired hepatocyte survival, enhanced liver damage and increased serum lipid levels in vivo and in vitro. Inhibition of miR-122 in ADEs alleviated NAFLD progression, lipid and glucose metabolism, liver inflammation and fibrosis both in vivo and in vitro. miR-122 binds directly to the 3′UTR of Sirt1 to suppress its expression. Moreover, Sirt1 overexpression reversed the increase in cell apoptosis, glucose and lipid metabolism, liver inflammation and fibrosis induced by ADEs in vivo and in vitro. Conclusions: The ADEs miR-122 promotes the progression of NAFLD via modulating Sirt1 signalling in vivo and in vitro. The ADEs miR-122 may be a promising diagnostic biomarker and therapeutic target for NAFLD.(AU)

Objetivos: La enfermedad del hígado graso no alcohólico (EHGNA) es una enfermedad hepática crónica que afecta a la función adiposa. Este estudio tiene como objetivo explorar la función de los exosomas derivados de los adipocitos (ADEs) miR-122 en la EHGNA. Métodos: Se estableció un modelo de rata inducido por una dieta alta en grasas y fructosa y un modelo in vitro inducido por ácido palmítico (AP). Se midió el nivel de ARN de miR-122 y Sirt1 mediante qRT-PCR. Los niveles de proteína de los biomarcadores de exosomas y los biomarcadores de lipogénesis, inflamación y fibrosis se determinaron mediante western blotting. La viabilidad celular y la apoptosis se evaluaron mediante el kit de recuento de células-8 y la citometría de flujo, respectivamente. Se midieron los niveles séricos de alanina aminotransferasa, aspartato aminotransferasa, colesterol total y triglicéridos. El daño tisular del hígado se evaluó mediante tinción con hematoxilina y eosina. La interacción entre miR-122 y Sirt1 3’UTR se evaluó mediante un ensayo de gen reportero de luciferasa. Resultados: Los ADEs mostraron un nivel abundante de miR-122 y promovieron la lipogénesis, perjudicaron la supervivencia de los hepatocitos, potenciaron el daño hepático y aumentaron los niveles de lípidos séricos in vivo e in vitro. La inhibición de miR-122 en los ADEs alivió la progresión de la EHGNA, el metabolismo de los lípidos y la glucosa, la inflamación del hígado y la fibrosis tanto in vivo como in vitro. miR-122 se une directamente a la 3’UTR de Sirt1 para suprimir su expresión. Además, la sobreexpresión de Sirt1 revirtió el aumento de la apoptosis celular, el metabolismo de la glucosa y los lípidos, la inflamación del hígado y la fibrosis inducida por los ADEs in vivo e in vitro. Conclusiones: El ADEs miR-122 promueve la progresión de la EHGNA a través de la modulación de la señalización de Sirt1 in vivo e in vitro...(AU)

Asociación de la gamma glutamil transferasa con la presencia y progresión de calcificaciones aórticas abdominales y con cambios en densidad mineral ósea / Association of gamma glutamyl transferase in the presence and progression of abdominal aortic calcifications and changes to bone mineral density

Introducción y objetivo: la calcificación aórtica abdominal (CAA) es predictora de eventos cardiovasculares. El objetivo de este trabajo fue valorar la asociación de la gamma glutamil transferasa (GGT) con presencia y progresión de CAA y los cambios en densidad mineral ósea (DMO) en columna lumbar y cuello femoral. Material y métodos: se seleccionaron 326 hombres y mujeres mayores de 50 años que realizaron un cuestionario, dos radiografías laterales dorso-lumbares y DMO, repitiendo a los 4 años las mismas pruebas y un estudio analítico. Resultados: la presencia y progresión de CAA (nuevas o mayor severidad) fue inferior en el cuartil 1 (Q1) de GGT respecto a los otros cuartiles (40 % vs. 58 %, p = 0,021; 24 % vs. 44 %, p = 0,022). Comparado con Q1, el análisis de regresión logística ajustado por confusores mostró que los Q2 y Q4 se asociaron con aumentos en la presencia de CAA [odds ratio (OR) = 2,53, intervalo de confianza del 95 % (IC 96 %) = (1,22-5,25) y OR = 3,04, IC 95 % = (1,36-6,77)] y Q2, Q3 y Q4 se asociaron con aumentos en progresión de CAA [OR = 2,24, IC 95 % = (1,07-4,67); OR = 2,35, IC 95 % = (1,09-5,07) y OR = 3,47, IC 95 % = (1,56-7,70)]. El análisis multivariante por sexos mostró que tanto en hombres como mujeres el Q4 de GGT se asoció con progresión de CAA [OR = 3,27, IC 95 % = (1,14-9,36) y OR = 3,26, IC 95 % = (1,03-10,29) respectivamente] y en mujeres con mayores pérdidas de DMO a nivel lumbar. No hubo efecto con respecto a la prevalencia de CAA. Conclusiones: valores elevados de GGT podrían ser un indicador de presencia y progresión de CAA en población mayor de 50 años. De forma separada por sexo, los mayores niveles de GGT se asociaron con progresión de CAA, siendo un marcador pronóstico de daño cardiovascular.(AU)

Introduction and objective: abdominal aortic calcification (AAC) is a predictor of cardiovascular events. This study aimedto assess the association of gamma glutamyl transferase (GGT) in the presence and progression of AAC, as well as changesto bone mineral density (BMD) in the lumbar spine and femoral neck.Materials and methods: a total of 326 men and women over 50 years of age were selected for this study. They completeda questionnaire, underwent two lateral dorso-lumbar spine X-rays, and BMD measurements. The same tests and 1 analyticalassessment were repeated after 4 years.Results: the presence and progression of AAC (new occurrences or increased severity) were lower in GGT quartile 1 (Q1)compared with the other quartiles (40 % vs 58 %; p = 0.021; 24 % vs 44 %; p = 0.022). Compared with Q1, the confound -ers-adjusted logistic regression analysis showed that Q2 and Q4 were associated with more presence of AAC [odds ratio(OR), 2.53; 95 % confidence interval (95 % CI), 1.22-5.25 and OR, 3.04; 95 % CI, 1.36-6.77]. Additionally, Q2, Q3, and Q4were associated with more AAC progression [OR, 2.24; 95 % CI, 1.07-4.67; OR, 2.35; 95 % CI, 1.09-5.07; and OR, 3.47;95 % CI, 1.56-7.70]. The gender-stratified multivariate analysis revealed that in both men and women, the Q4 of GGT wasassociated with AAC progression [OR, 3.27; 95 % CI, 1.14-9.36, and OR, 3.26; 95 % CI, 1.03-10.29, respectively], and inwomen alone, with greater lumbar BMD losses. There were no effects regarding the prevalence of AAC.Conclusions: elevated GGT levels could serve as an indicator of the presence and progression of AAC in individuals olderthan 50 years. When analyzed separately by gender, higher GGT levels were associated with AAC progression, which actedas a prognostic marker for cardiovascular disease.(AU)

Weight and metabolic changes in early psychosis-association with daily quantification of medication exposure during the first hospitalization.

BACKGROUND: The most common causes of death in schizophrenia are cardiovascular disorders, which are closely related to metabolic syndrome/obesity. To better understand the development of metabolic alterations early in the course of illness, we quantified daily medication exposure in the first days of the first hospitalization for psychosis and related it to changes in weight and metabolic markers. STUDY DESIGN: We recruited participants with first episode psychosis (FEP, N = 173) during their first psychiatric hospitalization and compared them to controls (N = 204). We prospectively collected weight, body mass index, metabolic markers, and exact daily medication exposure at admission and during hospitalization. STUDY RESULTS: Individuals with FEP gained on average 0.97 ± 2.26 BMI points or 3.46 ± 7.81 kg of weight after an average of 44.6 days of their first inpatient treatment. Greater antipsychotic exposure was associated with greater BMI increase, but only in people with normal/low baseline BMI. Additional predictors of weight gain included type of medication and duration of treatment. Medication exposure was not directly related to metabolic markers, but higher BMI was associated with higher TGC, TSH, and lower HDL. Following inpatient treatment, participants with FEP had significantly higher BMI, TGC, prolactin, and lower fT4, HDL than controls. CONCLUSION: During their first admission, people with FEP, especially those with normal/low baseline BMI, showed a rapid and clinically significant weight increase, which was associated with exposure to antipsychotics, and with metabolic changes consistent with metabolic syndrome. These findings emphasize weight monitoring in FEP and suggest a greater need for caution when prescribing metabolically problematic antipsychotics to people with lower BMI.

Dietary inflammatory index and its association with leptin and adiponectin in uygur overweight/obese adults / Índice de inflamación de la dieta y su relación con la leptina y la adiponectina en adultos de Uygur con sobrepeso/obesidad

Introduction: chronic inflammation contributes to a wide range of metabolic disorders through the influence of diet. The dietary inflammatory index (DII) was developed to measure the inflammation potential of diet. Objectives: Uygur adults have a high prevalence of obesity, but the causes of this condition remain unclear. In this study we investigated the association between DII and adipocytokines among overweight and obese Uygur adults. Methods: a total of 283 obese and overweight Uygur adults were included. Sociodemographic characteristics, anthropometric measurements, dietary surveys and biochemical indicators were collected by standardized protocols. The DII score was calculated using a valid and reliable 93-item food frequency questionnaire (FFQ). Linear regression was used to estimate the relationship between DII and adipocytokines. Results: the DII score was 1.35 ± 1.08, ranging from -2.14 to +3.11. There was a significant inverse correlation between DII and high-density lipoprotein cholesterol (HDL-C) in the unadjusted model (β = -0.12, SE = 0.05, p = 0.02), and this remained after adjustment for age, gender, body mass index (BMI). DII was negatively associated with adiponectin (ADPN) ( = -203.15, p = 0.04) and positively associated with leptin (LEP) concentration ( = 1.64, p = 0.002) after adjustment for age, gender and BMI. Conclusion: a pro-inflammatory diet, as indicated by a higher DII score, is associated with adipose tissue inflammation in Uygur adults and supports the hypothesis that diet may play a role in the development of obesity through inflammatory modulation mechanisms. A healthy anti-inflammatory diet is feasible for obesity intervention in the future.(AU)

Introducción: la inflamación crónica causa múltiples trastornos metabólicos a través de la influencia de la dieta. El índice de inflamación dietética(DII) se estableció para medir el potencial inflamatorio de la dieta.Objetivo: los adultos de Uygur presentan una alta prevalencia de obesidad, pero las causas de esta condición aún no están claras. En el presenteestudio se investigó la relación entre DII y adipocitocinas en adultos uigur con sobrepeso y obesidad.Métodos: se incluyeron 283 adultos de Uygur obesos y con sobrepeso. Las características sociodemográficas, antropométricas, dietéticas ybioquímicas se recogieron mediante un protocolo estandarizado. El índice DII se calculó utilizando un cuestionario de frecuencia alimentaria (FFQ)válido y fiable de 93 elementos. Se realizó una regresión lineal para estimar la relación entre DII y adipocitocinas.Resultados: la puntuación DII fue de 1,35 ± 1,08 y osciló entre -2,14 y +3,11. En el modelo no ajustado hubo una correlación negativa signi-ficativa entre DII y colesterol lipoproteínico de alta densidad (HDL-C) (β = -0,12, p = 0,02) que permaneció después de ajustar la edad, el sexoy el índice de masa corporal (IMC). Después de ajustar la edad, el sexo y el IMC, el DII se correlacionó negativamente con la concentración deadiponectina (β = - 203,15, p = 0,04) y positivamente con la concentración de leptina (β = 1,64, p = 0002).Conclusión: las puntuaciones más altas de DII sugieren que la dieta proinflamatoria está relacionada con la inflamación del tejido adiposo enlos adultos de Uygur, y apoyan la hipótesis de que la dieta puede desempeñar un papel en el desarrollo de la obesidad a través del mecanismode regulación de la inflamación. La dieta antiinflamatoria saludable es factible para futuras intervenciones de obesidad.(AU)

Linear Response Theory of Evolved Metabolic Systems.

Predicting cellular metabolic states is a central problem in biophysics. Conventional approaches, however, sensitively depend on the microscopic details of individual metabolic systems. In this Letter, we derived a universal linear relationship between the metabolic responses against nutrient conditions and metabolic inhibition, with the aid of a microeconomic theory. The relationship holds in arbitrary metabolic systems as long as the law of mass conservation stands, as supported by extensive numerical calculations. It offers quantitative predictions without prior knowledge of systems.

Ancestry-driven metabolite variation provides insights into disease states in admixed populations.

BACKGROUND: Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk. METHODS: We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data. RESULTS: By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent. CONCLUSIONS: Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.