Obesity rates among children are growing rapidly worldwide, placing massive pressure on healthcare systems. Untargeted metabolomics can expand our understanding of the pathogenesis of obesity and elucidate mechanisms related to its symptoms. However, the metabolic signatures of obesity in children have not been thoroughly investigated. Herein, we explored metabolites associated with obesity development in childhood. Untargeted metabolomic profiling was performed on fasting serum samples from 27 obese Caucasian children and adolescents and 15 sex- and age-matched normal-weight children. Three metabolomic assays were combined and yielded 726 unique identified metabolites: gas chromatography–mass spectrometry (GC–MS), hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC–MS/MS), and lipidomics. Univariate and multivariate analyses showed clear discrimination between the untargeted metabolomes of obese and normal-weight children, with 162 significantly differentially expressed metabolites between groups. Children with obesity had higher concentrations of branch-chained amino acids and various lipid metabolites, including phosphatidylcholines, cholesteryl esters, triglycerides. Thus, an early manifestation of obesity pathogenesis and its metabolic consequences in the serum metabolome are correlated with altered lipid metabolism. Obesity metabolite patterns in the adult population were very similar to the metabolic signature of childhood obesity. Identified metabolites could be potential biomarkers and used to study obesity pathomechanisms.

Background: Male fertility is known to have been negatively influenced by the progress of civilization. Another condition whose incidence has been on the increase for the same reason is insulin resistance (IR). In addition, men increasingly often resign from the pursuit of active forms of leisure, preferring more sedentary ones. Considering these trends, this aim of this study was to investigate the relationships between lifestyle factors, insulin resistance, and male fertility in men with and without the condition. A further aim was to select those lifestyle factors that would make it possible to predict the level of male fertility, especially when IR is concerned. Methods: This study was performed in a group of 73 participants, divided into groups based on their insulin resistance status. Their physical activity, diet, perceived stress, sleep quality, libido level, and duration of sexual abstinence were assessed on the basis of a number of parameters, including indices proposed by the authors. In addition, relevant anthropometric measurements were taken and tests related to glucose metabolism and semen quality were carried out. On the basis of these data, statistical tests were performed to establish or disprove relationships between lifestyle choices and semen quality, as measured my sperm motility. Results: The results of this study highlighted the associations between a number of parameters, i.e., micronutrient and vitamin intake, diet quality, body composition, insulin resistance, and the duration of sexual abstinence, and semen quality, as measured by sperm motility. Significantly, the presence or absence of IR was linked to male fertility. A multivariate model was developed, incorporating parameters such as the Matsuda index, vitamin intake, and sexual abstinence duration, to predict motility scores. Conclusions: This study underscores the negative impact of modern civilization’s lifestyle choices on male fertility. Notably, vitamin and mineral consumption, especially from antioxidant-rich diets like the Mediterranean diet, emerged as key modifiable factors affecting fertility. Routine diagnostics for insulin resistance in fertility-related interventions is recommended. This study also highlights the importance of considering sexual abstinence duration during semen collection for accurate diagnostic results. Future research should focus on validating the proposed multivariate model and exploring the effects of lifestyle modifications, particularly vitamin supplementation, on fertility outcomes in men, especially in the context of IR.

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes, but its contribution to the early stages of dysglycemia remains poorly understood. By collecting a high-resolution stage-based spectrum of dysglycemia, our study fills this gap by evaluating derangement in both the function and quantity of mitochondria. We sampled mitochondria in skeletal muscle and subcutaneous adipose tissues of subjects with progressive advancement of dysglycemia under a three-month exercise intervention. Methods: We measured clinical metabolic parameters and gathered skeletal muscle and adipose tissue biopsies before and after the three-month exercise intervention. We then assayed the number of mitochondria via citrate synthase (CS) activity and functional parameters with high-resolution respirometry. Results: In muscle, there were no differences in mitochondrial quantity or function at baseline between normoglycemics and prediabetics. However, the intervention caused improvement in CS activity, implying an increase in mitochondrial quantity. By contrast in adipose tissue, baseline differences in CS activity were present, with the lowest CS activity coincident with impaired fasting glucose and impaired glucose tolerance (IFG + IGT). Finally, CS activity, but few of the functional metrics, improved under the intervention. Conclusions: We show that in prediabetes, no differences in the function or amount of mitochondria (measured by CS activity) in skeletal muscle are apparent, but in adipose tissue of subjects with IFG + IGT, a significantly reduced activity of CS was observed. Finally, metabolic improvements under the exercise correlate to improvements in the amount, rather than function, of mitochondria in both tissues.

Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores apigenin’s capacity to modulate cancer cell viability, emphasizing its roles beyond its minimal antioxidant activity attributed to its basic molecular structure devoid of hydroxyl groups. We investigated apigenin’s effects on two breast cancer cell lines, estrogen-dependent MCF-7 and non-estrogen-dependent MDA-MB-231 cells. Our findings reveal that apigenin exerts a dose-dependent cytotoxic and anti-migratory impact on these cells. Interestingly, both apigenin and doxorubicin—a standard chemotherapeutic agent—induced lipid droplet accumulation in a dose-dependent manner in MDA-MB-231 cells. This phenomenon was absent in MCF-7 cells and not evident when doxorubicin and apigenin were used concurrently, suggesting distinct cellular responses to these treatments that imply that their synergistic effects might be mediated through mechanisms unrelated to lipid metabolism. A further chemoinformatics analysis indicated that apigenin and doxorubicin might interact primarily at the level of ATP-binding cassette (ABC) transporter proteins, with potential indirect influences from the AKT and MYC signaling pathways. These results highlight the importance of understanding the nuanced interactions between apigenin and conventional chemotherapeutic drugs, as they could lead to more effective strategies for cancer treatment. This study underscores apigenin’s potential as a modulator of cancer cell dynamics through mechanisms independent of its direct antioxidant effects, thereby contributing to the development of flavonoid-based adjunct therapies in cancer management.

Background/Objective: Infertility affects approximately 10–15% couples in industrialized countries. It has numerous causes, including genetic and environmental factors, lifestyle choices, and physiological disorders. The increasing prevalence of infertility underlines the importance of research into interventions to improve reproductive health, with a strong focus on physical activity. Infertility research was traditionally mainly directed toward female health. Although the male factor is being increasingly accepted as being equally important, this area remains under-researched. The current review focuses on the impact of physical activity on male fertility through its effects on immune function, the cardiovascular system, hormonal balance, metabolism, and physical interaction with the male reproductive system. Materials and Methods: A comprehensive literature review of studies addressing the effects of physical activity on male fertility was conducted using PubMed/Medline, Scopus, and the Web of Science. Mostly recent studies were included, with a small number of older ones included in cases when their content remains relevant. The review focused on articles studying the processes involved and associations between physical activity and male fertility through immune and cardiovascular effects, endocrine modulation, the influence on obesity and insulin metabolism, and the physical impact on the body. Results: The findings revealed the existence of a fairly strong consensus that moderate physical activity enhances semen quality, hormonal balance, and metabolic health, positively influencing male fertility. Physical activity reduces inflammation and oxidative stress, enhances cardiovascular functioning, and contributes to oxygen and nutrient supply to the reproductive organs. On the contrary, strenuous training can adversely affect fertility, mostly through hormonal disruption and oxidative stress. It can also have various indirect effects on fertility through sports-related behavior and incidents, such as wearing tight-fitting clothes or overheating. Conclusions: Physical activity can affect male fertility in numerous ways, positively influencing reproductive health when performed at a moderate intensity. Understanding the balance between beneficial and excessive exercise as well as the impact of incidental factors related to performing sports regularly are, thus, extremely important in optimizing lifestyle-oriented interventions aimed at male fertility improvement.

Prediabetes is an intermediate state of hyperglycemia during which glycemic parameters are above normal levels but below the T2D threshold. T2D and its precursor prediabetes affect 6.28% and 7.3% of the world’s population, respectively. The main objective of this paper was to create and compare two polygenic risk scores (PRSs) versus changes over time (Δ) in metabolic parameters related to prediabetes and metabolic complications. The genetics of 446 prediabetic patients from the Polish Registry of Diabetes cohort were investigated. Seventeen metabolic parameters were measured and compared at baseline and after five years using statistical analysis. Subsequently, genetic polymorphisms present in patients were determined to build a T2D PRS (68 SNPs) and an obesity PRS (21 SNPs). Finally, the association among the two PRSs and the Δ of the metabolic traits was assessed. After a multiple linear regression with adjustment for age, sex, and BMI at a nominal significance of (p < 0.05) and adjustment for multiple testing, the T2D PRS was found to be positively associated with Δ fat mass (FM) (p = 0.025). The obesity PRS was positively associated with Δ FM (p = 0.023) and Δ 2 h glucose (p = 0.034). The comparison of genotype frequencies showed that AA genotype carriers of rs10838738 were significantly higher in Δ 2 h glucose and in Δ 2 h insulin. Our findings suggest that prediabetic individuals with a higher risk of developing T2D experience increased Δ FM, and those with a higher risk of obesity experience increased Δ FM and Δ two-hour postprandial glucose. The associations found in this research could be a powerful tool for identifying prediabetic individuals with an increased risk of developing T2D and obesity.