406 research outputs found
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
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
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)
Iron Metabolism in Obesity and Metabolic Syndrome
Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity
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
Tight big-Ms for optimal transmission switching
This paper addresses the Optimal Transmission Switching (OTS) problem in electricity networks, which aims to find an optimal power grid topology that minimizes system operation costs while satisfying physical and operational constraints. Existing methods typically convert the OTS problem into a Mixed-Integer Linear Program (MILP) using big-M constants. However, the computational performance of these approaches relies significantly on the tightness of these big-Ms. In this paper, we propose an iterative tightening strategy to strengthen the big-Ms by efficiently solving a series of bounding problems that account for the economics of the OTS objective function through an upper-bound on the generating cost. We also discuss how the performance of the proposed tightening strategy is enhanced if reduced line capacities are considered. Using the 118-bus test system we demonstrate that the proposed methodology outperforms existing approaches, offering tighter bounds and significantly reducing the computational burden of the OTS problem.Funding for open access charge: Universidad de Málaga / CBU
Analysis of Sport Supplement Consumption and Body Composition in Spanish Elite Rowers.
The aim of this study was to analyze the anthropometric characteristics and sport
supplement (SS) consumption patterns of heavyweight and lightweight international rowers. Methods:
The 13 heavyweights (11 males) and seven lightweights (five males) of the Spanish National Rowing
Team were recruited for the study. Body composition was measured by bio-impedance analysis,
and the questionnaire used in this investigation was previously validated to assess SS consumption.
According to anthropometrics parameters, it was reported that male heavyweight rowers were heavier
(p < 0.001) and taller (p < 0.001), but no statistical di erences were reported for % body fat (p = 0.104)
or % lean body mass (p = 0.161). All rowers reported consumption of at least one SS. Based on the
Australian Institute of Sport’s classification, higher medical supplement consumption was observed
when comparing heavyweight rowers to lightweight rowers (2.5 1.1 vs. 1.7 0.5, p = 0.040). There
were no di erences in the totals of group A (strong scientific evidence for sports scenarios, p = 0.069),
group B (emerging scientific support, deserving of further research, p = 0.776), or group C (scientific
evidence not supportive of benefit and/or security amongst athletes, p = 0.484). The six most consumed
SSs were iron (85%), ca eine (85%), -alanine (85%), energy bars (85%), vitamin supplements (80%),
and isotonic drinks (80%), with no statistical di erences between heavyweight and lightweight rowers
(p > 0.05). These results suggest that the absence of di erences in body composition (expressed as a
percentage) do not represent anthropometric disadvantages for heavyweight rowers. In addition,
SS consumption was similar between rowers, reporting only higher medical supplement consumption
in heavyweight rowers.post-print931 K
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