Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity

Background: Trace elements and heavy metals have proven pivotal roles in childhood obesity and insulin resistance. However, growing evidence suggests that insulin resistance could encompass distinct phenotypic subtypes. Methods: Herein, we performed a comprehensive metallomics characterization of plasma samples from children and adolescents with obesity and concomitant insulin resistance, who were stratified as early (N = 17, 11.4 ± 2.4 years), middle (N = 16, 11.8 ± 1.9 years), and late (N = 33, 11.7 ± 2.0 years) responders according to the insulin secretion profile in response to an oral glucose tolerance test. To this end, we employed a high-throughput method aimed at determining the biodistribution of various essential and toxic elements by analyzing total metal contents, metal-containing proteins, and labile metal species. Results: Compared with the early responders, participants with delayed glucose-induced hyperinsulinemia showed a worsened insulin resistance (HOMA-IR, 4.5 vs. 3.8) and lipid profile (total cholesterol, 160 vs. 144 mg/dL; LDL-cholesterol, 99 vs. 82 mg/dL), which in turn was accompanied by sharpened disturbances in the levels of plasmatic proteins containing chromium (4.8 vs. 5.1 µg/L), cobalt (0.79 vs. 1.2 µg/L), lead (0.021 vs. 0.025 µg/L), and arsenic (0.077 vs. 0.17 µg/L). A correlation analysis demonstrated a close inter-relationship among these multielemental perturbations and the characteristic metabolic complications occurring in childhood obesity, namely impaired insulin-mediated metabolism of carbohydrates and lipids. Conclusions: These findings highlight the crucial involvement that altered metal homeostasis and exposure may have in regulating insulin signaling, glucose metabolism, and dyslipidemia in childhood obesity.This research was funded by the Spanish Government through Instituto de Salud Carlos III (PI22/01899). AGD is supported by an intramural grant from the Biomedical Research and Innovation Institute of Cádiz (LII19/16IN-CO24), and RGD is a recipient of a “Miguel Servet” fellowship (CP21/00120) funded by Instituto de Salud Carlos III

Exploring the association between circulating trace elements, metabolic risk factors, and the adherence to a Mediterranean diet among children and adolescents with obesity

Diet is one of the most important modifiable lifestyle factors for preventing and treating obesity. In this respect, the Mediterranean diet (MD) has proven to be a rich source of a myriad of micronutrients with positive repercussions on human health. Herein, we studied an observational cohort of children and adolescents with obesity (N = 26) to explore the association between circulating blood trace elements and the degree of MD adherence, as assessed through the KIDMED questionnaire. Participants with higher MD adherence showed better glycemic/insulinemic control and a healthier lipid profile, as well as raised plasma levels of selenium, zinc, cobalt, molybdenum, and arsenic, and increased erythroid content of selenium. Interestingly, we found that these MD-related mineral alterations were closely correlated with the characteristic metabolic complications behind childhood obesity, namely hyperglycemia, hyperinsulinemia, and dyslipidemia (p 0.35). These findings highlight the pivotal role that dietary trace elements may play in the pathogenesis of obesity and related disorders.This research was partially funded by the Spanish Government through Instituto de Salud Carlos III- (PI22/01899). ÁG-D was supported by an intramural grant from the Biomedical Research and Innovation Institute of Cádiz (LII19/16INCO24), and RG-D was recipient of a “Miguel Servet” fellowship (CP21/00120) funded by Instituto de Salud Carlos III

Sexually dimorphic metal alterations in childhood obesity are modulated by a complex interplay between inflammation, insulin, and sex hormones

Although growing evidence points to a pivotal role of perturbed metal homeostasis in childhood obesity, sexual dimorphisms in this association have rarely been investigated. In this study, we applied multi-elemental analysis to plasma and erythrocyte samples from an observational cohort comprising children with obesity, with and without insulin resistance, and healthy control children. Furthermore, a wide number of variables related to carbohydrate and lipid metabolism, inflammation, and sex hormones were also determined. Children with obesity, regardless of sex and insulin resistance status, showed increased plasma copper-to-zinc ratios. More interestingly, obesity-related erythroid alterations were found to be sex-dependent, with increased contents of iron, zinc, and copper being exclusively detected among female subjects. Our findings suggest that a sexually dimorphic hormonal dysregulation in response to a pathological cascade involving inflammatory processes and hyperinsulinemia could be the main trigger of this female-specific intracellular sequestration of trace elements. Therefore, the present study highlights the relevance of genotypic sex as a susceptibility factor influencing the pathogenic events behind childhood obesity, thereby opening the door to develop sex-personalized approaches in the context of precision medicine.INiBICA, Grant/Award Number: LII19/16IN-CO24; Instituto de Salud Carlos III, Grant/Award Numbers: CP21/00120, PI22/0189

Altered Metal Homeostasis Associates with Inflammation, Oxidative Stress, Impaired Glucose Metabolism, and Dyslipidemia in the Crosstalk between Childhood Obesity and Insulin Resistance

Metals are redox-active substances that participate in central biological processes and may be involved in a multitude of pathogenic events. However, considering the inconsistencies reported in the literature, further research is crucial to disentangle the role of metal homeostasis in childhood obesity and comorbidities using well-characterized cohorts and state-of-the-art analytical methods. To this end, we studied an observational population comprising childrenwith obesity and insulin resistance, children with obesity without insulin resistance, and healthy control children. A multi-elemental approach based on the size-fractionation of metal species was applied to quantify the total content of various essential and toxic elements in plasma and erythrocyte samples, and to simultaneously investigate the metal fractions conforming the metalloproteome and the labile metal pool. The most important disturbances in childhood obesity were found to be related to elevated circulating copper levels, decreased content of plasmatic proteins containing chromium, cobalt, iron, manganese, molybdenum, selenium, and zinc, as well as the sequestration of copper, iron, and selenium within erythrocytes. Interestingly, these metal disturbances were normally exacerbated among children with concomitant insulin resistance, and in turn were associated to other characteristic pathogenic events, such as inflammation, oxidative stress, abnormal glucose metabolism, and dyslipidemia. Therefore, this study represents one-step further towards a better understanding of the involvement of metals in the crosstalk between childhood obesity and insulin resistance.This research was partially funded by the Spanish Government through Instituto de Salud Carlos III (CP21/00120, PI18/01316). Á.G.-D. is supported by an intramural grant from the Biomedical Research and Innovation Institute of Cádiz (LII19/16IN-CO24), and R.G.-D. is recipient of a “Miguel Servet” fellowship (CP21/00120) funded by Instituto de Salud Carlos III

Trace elements as potential modulators of puberty-induced amelioration of oxidative stress and inflammation in childhood obesity

Although puberty is known to influence obesity progression, the molecular mechanisms underlying the role of sexual maturation in obesity-related complications remains largely unexplored. Here, we delve into the impact of puberty on the most relevant pathogenic hallmarks of obesity, namely oxidative stress and inflammation, and their association with trace element blood status. To this end, we studied a well-characterized observational cohort comprising prepubertal (N = 46) and pubertal (N = 48) children with obesity. From all participants, plasma and erythrocyte samples were collected and subjected to metallomics analysis and determination of classical biomarkers of oxidative stress and inflammation. Besides the expected raise of sexual hormones, pubertal children displayed better inflammatory and oxidative control, as reflected by lower levels of C-reactive protein and oxidative damage markers, as well as improved antioxidant defense. This was in turn accompanied by a healthier multielemental profile, with increased levels of essential elements involved in the antioxidant system and metabolic control (metalloproteins containing zinc, molybdenum, selenium, and manganese) and decreased content of potentially deleterious species (total copper, labile free iron). Therefore, our findings suggest that children with obesity have an exacerbated inflammatory and oxidative damage at early ages, which could be ameliorated during pubertal development by the action of trace element-mediated buffering mechanisms.This research was funded by the Spanish Government through Instituto de Salud Carlos III (PI22/01899, PI18/01316). Állvaro González-Domínguez is supported by an intramural grant from the Biomedical Research and Innovation Institute of Cádiz (LII19/16IN-CO24), and Raúl González-Domínguez is recipient of a “Miguel Servet” fellowship funded by Instituto de Salud Carlos III (CP21/00120)

Determinants of the outcomes of services outsourcing: an empirical study of transport services.

The purpose of our study is to examine whether the design and management of the interfaces and interaction processes between customer and provider in services outsourcing are determinants of the results achieved by the outsourcing company. Following the conceptual framework initiated in the study by Wynstra et al. [11], this study focuses on transport services and hypothesized relationships are tested using the Partial Least Squares (PLS) statistical technique. The primary data used was obtained from a survey in three different countries (Germany, Japan and Spain), and from manufacturing companies in the electronics, automotive and machinery sectors. Among other things, the results show that both the structural dimensions of interaction (the organization's resources that it must commit) and the process dimensions of interaction (that consider the dynamic nature of the relationships), are important for obtaining adequate performance from transport services outsourcing.Spanish National Program of Industrial Design and Production DPI 2009 11148PAIDI Excellence Projects P08-SEJ0384

Assessment of Virgin Olive Oil Adulteration by a Rapid Luminescent Method

The adulteration of virgin olive oil with hazelnut oil is a common fraud in the food industry, which makes mandatory the development of accurate methods to guarantee the authenticity and traceability of virgin olive oil. In this work, we demonstrate the potential of a rapid luminescent method to characterize edible oils and to detect adulterations among them. A regression model based on five luminescent frequencies related to minor oil components was designed and validated, providing excellent performance for the detection of virgin olive oil adulteration

La arquitectura, un lugar para las mujeres

En el año 2010 se cumplió el centenario de la Real Orden del Ministerio de Instrucción Pública y Bellas Artes por la que se permitía la “admisión de mujeres en todos los establecimientos docentes”, publicada en La Gaceta de Madrid en 1910, siendo Ministro de la Gobernación el Excmo. Sr. D. Julio Burrel y Cuéllar, durante el reinado de Alfonso XIII. Esta Ponencia nace con la intención de celebrar los ciento un años de vigencia de esta Orden en el campo científico, glosando la historia personal y profesional de la madrileña Matilde Ucelay Maortúa, primera mujer arquitecta de nuestro país (Escuela de Arquitectura de la Universidad de Madrid, 1936). En la misma se muestran las numerosísimas dificultades que tuvo que superar Matilde para llevar a la práctica esa titulación, entre las que las de género ocupan un lugar preferencial

Matilde Ucelay: la primera mujer española arquitecta de la historia

Este artículo sigue la línea de otros anteriores de uno de sus autores, junto con otros colaboradores, destinados a glosar las figuras de mujeres españolas pioneras de las ciencias, aunque prácticamente desconocidas por la sociedad en razón de la escasa documentación que se posee sobre ellas. Al igual que en esos artículos anteriores, el estatus de éste no debe calificarse de original, al ser claramente divulgativo, amén de recopilatorio tanto de materiales hablados y previamente grabados pasados a texto como de las diferentes fuentes consultadas. Así, gran parte de su texto es una transcripción del contenido de archivos de audio de entrevistas realizadas a familiares de Matilde Ucelay y diversos arquitectos, por ejemplo, así como de trabajos de otros autores sobre la figura de Matilde, de entre los que deseamos destacar explícitamente el de Luis Alemany y sobre todo, el de Inés Sánchez de Madariaga3. Todas las transcripciones literales aparecen entrecomilladas en el artículo y parte del texto que media entre las citas está así mismo basado en la voz de audio