29 research outputs found
Condensados Biomoleculares: Organizadores de la Vida
Life never fails to surprise us. Today, it does so with membrane-less organelles known as biomolecular condensates. These structures arise from a phenomenon of biomolecular self-organization capable of generating localized microenvironments with defined functions within the cell. In recent years, the significance of condensates in various aspects of cellular biology has been unveiled, including the regulation of gene expression, protein synthesis, cellular signaling control, cytoskeletal protein polymerization, and the formation of aggregates associated with neurodegenerative diseases, among many others yet to be discovered. These findings are revolutionizing our current understanding of cellular processes and providing new insights into cell process regulation. Condensates unveil previously unknown cellular mechanisms, more stochastic, that are shifting away from the dominance of genetic mechanisms in favor of cellular self-organization processes. The advancement in comprehending biomolecular condensates paves the way for exciting avenues of research in cellular and molecular biology, enabling the reinterpretation of processes that relate the genotype to the phenotype. Offering, in this way, the potential to better understand diseases and develop more effective therapeutic approaches in the future.La vida nunca deja de sorprendernos. Hoy lo hace con unos orgánulos libres de membrana conocidos como condensados biomoleculares. Éstos, son el resultado de un fenómeno de autoorganización de biomoléculas capaz de crear auténticos microentornos con funciones definidas en el interior de la célula. En los últimos años, se ha descubierto que los condensados desempeñan un papel relevante en diversos aspectos de la biología celular, como la regulación de la expresión génica, la síntesis de proteínas, el control de la señalización celular, la polimerización de proteínas del citoesqueleto o la formación de agregados asociados a enfermedades neurodegenerativas, entre muchas otras aún por descubrir. Estos hallazgos están desafiando nuestra comprensión actual de los procesos celulares y ofrecen nuevas maneras de entender el funcionamiento interno de las células. Los condensados muestran mecanismos celulares previamente desconocidos, mucho más estocásticos y que diluyen la preponderancia del mecanicismo genético en favor de los procesos de autoorganización celular. El avance en la comprensión de los condensados biomoleculares abre emocionantes vías de investigación en biología celular y molecular y permiten la reinterpretación de los procesos que relacionan el genotipo y el fenotipo, ofreciendo así la posibilidad de comprender mejor las enfermedades y desarrollar enfoques terapéuticos más efectivos en el futuro
A surgical model of short bowel syndrome induces a long-lasting increase in pancreatic beta-cell mass
Several surgical techniques are used nowadays as a severe treatment for obesity and diabetes mellitus type 2. These techniques are aggressive due to drastic changes in the nutrient flow and non-reversible modifications on the digestive tube. In this paper we present the effects of a massive intestinal resection on the pancreas. Results have shown that short bowel technique is less aggressive to normal anatomy and physiology of the intestinal tract than Gastric bypass or biliopancreatic diversion (e.g.). In this paper we reproduce a model of short bowel syndrome (SIC), with similar surgical conditions and clinical complications as seen in human cases. This work was conducted on normal Wistar rats, with no other concurrent factors, in order to determine the effects on normal pancreas islets.
We measured pancreatic implications by histomorphometric studies, which included beta-cell mass by immunocytochemistry, and apoptosis/proliferation test with TUNEL technique and Ki-67. Briefly, we reported on an increased relative area of the islets of the pancreas, as well as an increase in the average size of islets in the
SIC versus the control group. Furthermore we stated that this increase in size of the pancreatic islets is due to the
mechanisms of proliferation of beta cells in animals undergoing SIC. These goals could reveal a direct
influence of surgical modification of the digestive tract over the pancreatic beta cell homeostasis. In this sense,
there are many potential stimulators of intestinal adaptation, including peptide hormones and growth
components which are associated or involved as effectors of the endocrine pancreas
Impact of Parental Food Choices on Nutritional and Metabolic Status of Children with Type 1 Diabetes
Parents play a key role in what their children eat. The Food Choice Questionnaire (FCQ) has been used elsewhere to assess the dietary motivations of parents of healthy children, but not for parents of children with chronic diseases such as type 1 diabetes (T1D). The aim of our research was to evaluate the associations between parental food choice motivations and the nutritional status and glycemic control of children with T1D. A cross-sectional observational study of children aged 5 to 16 years with T1D attending the Pediatric Endocrinology Unit of Puerta del Mar University Hospital in Cádiz (Spain) was performed. Demographic, anthropometric and clinical data, including glycated hemoglobin, were collected. The FCQ in Spanish was conducted to assess the eating behaviors of the main caregivers of children with T1D. Significance was established at the level of p-value < 0.05. In total, 85 children with T1D (female 56.5%, age 12.07 ± 2.93 years, HbA1c 7.29 ± 0.77%) were recruited. Of these children, 31.3% showed HbA1c levels of [removed]70%. A significant positive correlation was found between Hb1Ac and “familiarity” (R: +0.233). Anthropometric measures (weight, BMI, skinfolds and body circumferences) showed significant positive correlations with “sensory appeal” and “price”. Parents’ eating behaviors influence the nutritional status of their children with T1D and their glycemic control of the disease.11 página
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
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 g/L), cobalt (0.79 vs. 1.2 g/L),
lead (0.021 vs. 0.025 g/L), and arsenic (0.077 vs. 0.17 g/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
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)
Mechanistic Insights into Alzheimer’s Disease Unveiled through the Investigation of Disturbances in Central Metabolites and Metabolic Pathways
Hydrophilic metabolites are closely involved in multiple primary metabolic pathways and, consequently, play an essential role in the onset and progression of multifactorial human disorders, such as Alzheimer's disease. This review article provides a comprehensive revision of the literature published on the use of mass spectrometry-based metabolomics platforms for approaching the central metabolome in Alzheimer's disease research, including direct mass spectrometry, gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Overall, mounting evidence points to profound disturbances that affect a multitude of central metabolic pathways, such as the energy-related metabolism, the urea cycle, the homeostasis of amino acids, fatty acids and nucleotides, neurotransmission, and others