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1.
Nefrología (Madrid) ; 44(2): 204-216, Mar-Abr. 2024. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-231570

RESUMO

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)


Assuntos
Humanos , Tacrolimo , Transplante de Rim , Farmacocinética , Farmacogenética , Metabolismo , Dosagem
2.
J. physiol. biochem ; 80(1): 41-51, Feb. 2024. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-229939

RESUMO

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)


Assuntos
Animais , Camundongos , Proteínas Associadas à Doença de Parkinson , Peptídeos e Proteínas de Sinalização Intercelular , Envelhecimento , Tecido Adiposo , Metabolismo
3.
J. physiol. biochem ; 80(1): 161-173, Feb. 2024. graf
Artigo em Inglês | IBECS | ID: ibc-229948

RESUMO

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)


Assuntos
Humanos , Pessoa de Meia-Idade , Resposta ao Choque Térmico , Treinamento de Força , Proteínas de Choque Térmico HSP70 , Estresse Oxidativo , Inflamação , Metabolismo
4.
Int. microbiol ; 27(1): 49-66, Feb. 2024. graf
Artigo em Inglês | IBECS | ID: ibc-230243

RESUMO

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)


Assuntos
Humanos , Methylomonas/metabolismo , Nitrogênio/metabolismo , Carbono/química , Metabolismo/genética , Metanol , Microbiologia , Técnicas Microbiológicas
5.
J. physiol. biochem ; 80(1): 41-51, Feb. 2024. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-EMG-564

RESUMO

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)


Assuntos
Animais , Camundongos , Proteínas Associadas à Doença de Parkinson , Peptídeos e Proteínas de Sinalização Intercelular , Envelhecimento , Tecido Adiposo , Metabolismo
6.
J. physiol. biochem ; 80(1): 161-173, Feb. 2024. graf
Artigo em Inglês | IBECS | ID: ibc-EMG-574

RESUMO

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)


Assuntos
Humanos , Pessoa de Meia-Idade , Resposta ao Choque Térmico , Treinamento de Força , Proteínas de Choque Térmico HSP70 , Estresse Oxidativo , Inflamação , Metabolismo
8.
Cambios rev. méd ; 22 (2), 2023;22(2): 919, 16 octubre 2023. ilus, tabs
Artigo em Espanhol | LILACS | ID: biblio-1516520

RESUMO

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.


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biológicos , Envelhecimento , Senescência Celular , Genes , Genética , Longevidade , Qualidade de Vida , Expectativa de Vida , Apoptose , Estresse Oxidativo , Telomerase , Senilidade Prematura , Equador , Sistema Imunitário , Metabolismo
9.
Nutr. hosp ; 40(5): 975-983, SEPTIEMBRE-OCTUBRE, 2023. tab
Artigo em Inglês | IBECS | ID: ibc-226298

RESUMO

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)


Assuntos
Humanos , Feminino , Fenótipo , Metabolismo , Menopausa/metabolismo , Tireotropina/metabolismo , Estudos Transversais , Treinamento de Força , Obesidade Metabolicamente Benigna
10.
Gastroenterol. hepatol. (Ed. impr.) ; 46(7): 531-541, Ago-Sep. 2023. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-222852

RESUMO

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)


Assuntos
Humanos , Animais , Sirtuínas , Hepatopatia Gordurosa não Alcoólica , Metabolismo , Adipócitos , Gastroenterologia , Gastroenteropatias
11.
Rev. osteoporos. metab. miner. (Internet) ; 15(3): 93-99, Juli-Sep. 2023. tab
Artigo em Inglês, Espanhol | IBECS | ID: ibc-226993

RESUMO

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)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , gama-Glutamiltransferase , Densidade Óssea , Coluna Vertebral , Colo do Fêmur/metabolismo , Densitometria , Metabolismo , Osteoporose , Inquéritos e Questionários , Fatores de Risco
12.
Nutr. hosp ; 40(4): 739-745, Juli-Agos. 2023. tab
Artigo em Inglês | IBECS | ID: ibc-224197

RESUMO

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)


Assuntos
Humanos , Sobrepeso , Obesidade , Antropometria , Leptina , Adiponectina , Dieta/efeitos adversos , China , 52503 , Inflamação , Metabolismo
13.
Genome Med ; 15(1): 52, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37461045

RESUMO

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.


Assuntos
Estudo de Associação Genômica Ampla , Hispânico ou Latino , Espectrometria de Massas em Tandem , Humanos , População Negra/genética , Genoma Humano , Estudo de Associação Genômica Ampla/métodos , Hispânico ou Latino/genética , Polimorfismo de Nucleotídeo Único , Indígena Americano ou Nativo do Alasca/genética , Metabolismo/genética , Grupos Populacionais/etnologia , Grupos Populacionais/genética
14.
Phys Rev Lett ; 131(2): 028401, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37505963

RESUMO

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.


Assuntos
Metabolismo , Modelos Biológicos
15.
J Steroid Biochem Mol Biol ; 232: 106349, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37321512

RESUMO

Membrane contact sites (MCS) make up a crucial route of inter-organelle non-vesicular transport within the cell. Multiple proteins are involved in this process, which includes the ER-resident proteins vesicle associated membrane protein associated protein A and -B (VAPA/B) that form MCS between the ER and other membrane compartments. Currently most functional data on VAP depleted phenotypes have shown alterations in lipid homeostasis, induction of ER stress, dysfunction of UPR and autophagy, as well as neurodegeneration. Literature on concurrent silencing of VAPA/B is still sparse; therefore, we investigated how it affects the macromolecule pools of primary endothelial cells. Our transcriptomics results showed significant upregulation in genes related to inflammation, ER and Golgi dysfunction, ER stress, cell adhesion, as well as Coat Protein Complex-I and -II (COP-I, COP-II) vesicle transport. Genes related to cellular division were downregulated, as well as key genes of lipid and sterol biosynthesis. Lipidomics analyses revealed reductions in cholesteryl esters, very long chain highly unsaturated and saturated lipids, whereas increases in free cholesterol and relatively short chain unsaturated lipids were evident. Furthermore, the knockdown resulted in an inhibition of angiogenesis in vitro. We speculate that ER MCS depletion has led to multifaceted outcomes, which include elevated ER free cholesterol content and ER stress, alterations in lipid metabolism, ER-Golgi function and vesicle transport, which have led to a reduction in angiogenesis. The silencing also induced an inflammatory response, consistent with upregulation of markers of early atherogenesis. To conclude, ER MCS mediated by VAPA/B play a crucial role in maintaining cholesterol traffic and sustain normal endothelial functions.


Assuntos
Retículo Endoplasmático , Membranas Intracelulares , Humanos , Células Endoteliais da Veia Umbilical Humana , Retículo Endoplasmático/metabolismo , Membranas Intracelulares/metabolismo , Técnicas de Silenciamento de Genes , Metabolismo , Neovascularização Fisiológica , Colesterol/metabolismo , Esterificação , Lipidômica , Mapas de Interação de Proteínas , Complexo de Golgi/metabolismo , Complexo I de Proteína do Envoltório/metabolismo
16.
Rev. esp. salud pública ; 97: e202306053, Jun. 2023. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-222816

RESUMO

FUNDAMENTOS: La enfermedad hepática grasa asociada a disfunción metabólica (MAFLD) es una enfermedad poco considerada,que ha recibido atención debido al número de casos en países como México, donde ocupa el 4º lugar mundial de incidencia. La MAFLDse desarrolla en personas con sobrepeso u obesidad y se caracteriza por la acumulación de triglicéridos en el hígado, donde puedeevolucionar hacia carcinoma hepatocelular. Se ha observado que la MAFLD depende de la genética y del estilo de vida. Tomando encuenta la alta prevalencia de MAFLD en la población hispana, nos enfocamos en este trabajo en estudiar la prevalencia y características relacionadas con esta enfermedad en pacientes mexicanos. MÉTODOS: En este estudio se incluyeron 572 pacientes con sobrepeso u obesidad, a los cuales se les realizó un análisis de cribadomediante el índice de hígado graso (IHG), se analizaron parámetros clínicos, demográficos y comorbilidades. Se obtuvieron frecuenciasde las variables y se analizaron los datos mediante chi cuadrado o exacta de Fisher, razón de momios (OR) y regresión logística binaria. RESULTADOS: Se obtuvo una prevalencia del 37% de MAFLD, donde la historia familiar de obesidad, el uso de paracetamol, así comoel consumo de carbohidratos y grasas fueron factores de riesgo para su desarrollo. Se encontró que la hipertensión arterial, la obesidadvisceral y la hipertrigliceridemia también estaban asociados al desarrollo de la MAFLD. Por otro lado, el ejercicio fue un factor protector. CONCLUSIONES: Nuestros resultados ponen de manifiesto la necesidad de realizar estudios relacionados con las causalidades dela MAFLD en los pacientes mexicanos, principalmente en el uso del paracetamol.(AU)


BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a poor attended disease, which has gained at-tention due the elevated number of cases in countries as Mexico, where the incidence is the number 4 th globally. MAFLD developsin obese or overweighted individuals and is characterized by triglycerides accumulation in the liver, this condition can develop tohepatocellular carcinoma. It has been observed that MAFLD depends on the genetics and lifestyle. Due to the high prevalence of thisdisease among Hispanic population, we focused on this study in the characteristics and prevalence of MAFLD in Mexican patients. METHODS: In this study were included 572 overweighted and obese patients, who underwent a screening analysis using the fatty liverindex (IHG), clinical parameters were analysed, demographic and comorbidities. Frequency of variables were obtained, and the data wereanalysed by Chi-square test or Fisher test, odd ratio (OR) and binary logistic regression. RESULTS: A MALFD prevalence of 37% were obtained, where the history of familiar obesity, paracetamol usage, carbohydrate andfat intake are shown to be risk factors. It was found that high blood pressure, central obesity and hypertriglyceridemia were alsoassociated to the MAFLD development. On the other hand, physical exercise was a protector factor. CONCLUSIONS: Our results show the necessity to study the MAFLD causalities in Mexican patients, focused on the paracetamol intake.(AU)


Assuntos
Humanos , Masculino , Feminino , Hepatopatias , Metabolismo , Sobrepeso , Obesidade , Acetaminofen , Fígado Gorduroso , México , Saúde Pública , Fatores de Risco , Incidência , Prevalência
17.
Annu Rev Immunol ; 41: 317-342, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37126419

RESUMO

Over the last decade, immunometabolism has emerged as a novel interdisciplinary field of research and yielded significant fundamental insights into the regulation of immune responses. Multiple classical approaches to interrogate immunometabolism, including bulk metabolic profiling and analysis of metabolic regulator expression, paved the way to appreciating the physiological complexity of immunometabolic regulation in vivo. Studying immunometabolism at the systems level raised the need to transition towards the next-generation technology for metabolic profiling and analysis. Spatially resolved metabolic imaging and computational algorithms for multi-modal data integration are new approaches to connecting metabolism and immunity. In this review, we discuss recent studies that highlight the complex physiological interplay between immune responses and metabolism and give an overview of technological developments that bear the promise of capturing this complexity most directly and comprehensively.


Assuntos
Alergia e Imunologia , Imunidade , Metabolismo , Animais , Humanos , Biologia de Sistemas
18.
Annu Rev Nutr ; 43: 1-23, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37253680

RESUMO

An interview with James M. Ntambi, professor of biochemistry and the Katherine Berns Van Donk Steenbock Professor in Nutrition, College of Agricultural and Life Sciences, at the University of Wisconsin-Madison, took place via Zoom in April 2022. He was interviewed by Patrick J. Stover, director of the Institute for Advancing Health through Agriculture and professor of nutrition and biochemistry and biophysics at Texas A&M University. Dr. James Ntambi is a true pioneer in the field of nutritional biochemistry. He was among the very first to discover and elucidate the role that diet and nutrients play in regulating metabolism through changes in the expression of metabolic genes, focusing on the de novo lipogenesis pathways. As an African immigrant from Uganda, his love of science and his life experiences in African communities suffering from severe malnutrition molded his scientific interests at the interface of biochemistry and nutrition. Throughout his career, he has been an academic role model, a groundbreaking nutrition scientist, and an educator. His commitment to experiential learning through the many study-abroad classes he has hosted in Uganda has provided invaluable context for American students in nutrition. Dr. Ntambi's passion for education and scientific discovery is his legacy, and the field of nutrition has benefited enormously from his unique perspectives and contributions to science that are defined by his scientific curiosity, his generosity to his students and colleagues, and his life experiences. The following is an edited transcript.


Assuntos
Agricultura , Bioquímica , Ciências da Nutrição , Humanos , Agricultura/história , Metabolismo/genética , Ciências da Nutrição/história , Estado Nutricional , Uganda , Estados Unidos , Wisconsin , População Africana , Desnutrição/genética , Desnutrição/metabolismo , Bioquímica/história
19.
Endocr J ; 70(5): 453-457, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37245994
20.
Acta Physiol (Oxf) ; 238(3): e14003, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37223989
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