Prediabetes (PrDM) is a prodromal stage of diabetes mellitus (DM) with an increasing prevalence worldwide. During DM progression, individuals gradually develop complications in various organs. ...However, lungs are suggested to be affected later than other organs, such as the eyes, heart or brain. In this work, we studied the effects of PrDM on male Wistar rats’ lungs and whether the regular consumption of white tea (WTEA) for 2 months contributes to the improvement of the antioxidant profile of this tissue, namely through improved activity of the first line defense antioxidant enzymes, the total antioxidant capacity and the damages caused in proteins, lipids and histone H2A. Our data shows that PrDM induced a decrease in lung superoxide dismutase and glutathione peroxidase activities and histone H2A levels and an increase in protein nitration and lipid peroxidation. Remarkably, the regular WTEA intake improved lung antioxidant enzymes activity and total antioxidant capacity and re-established the values of protein nitration, lipid peroxidation and histone H2A. Overall, this is the first time that lung is reported as a major target for PrDM. Moreover, it is also the first report showing that WTEA possesses relevant chemical properties against PrDM-induced lung dysfunction.
Embryo quality evaluation during in vitro development is a crucial factor for the success of assisted reproductive technologies (ARTs). However, the subjectivity inherent in the morphological ...evaluation by embryologists can introduce inconsistencies that impact the optimal embryo choice for transfer. To provide a more comprehensive evaluation of embryo quality, we undertook the integration of embryo metabolomics alongside standardized morphokinetic classification. The culture medium of 55 embryos (derived from 21 couples undergoing ICSI) was collected at two timepoints (days 3 and 5). Samples were split into Good (n = 29), Lagging (n = 19), and Bad (n = 10) according to embryo morphokinetic evaluation. Embryo metabolic performance was assessed by monitoring the variation in specific metabolites (pyruvate, lactate, alanine, glutamine, acetate, formate) using
H-NMR. Adjusted metabolite differentials were observed during the first 3 days of culture and found to be discriminative of embryo quality at the end of day 5. Pyruvate, alanine, glutamine, and acetate were major contributors to this discrimination. Good and Lagging embryos were found to export and accumulate pyruvate and glutamine in the first 3 days of culture, while Bad embryos consumed them. This suggests that Bad embryos have less active metabolic activity than Good and Lagging embryos, and these two metabolites are putative biomarkers for embryo quality. This study provides a more comprehensive evaluation of embryo quality and can lead to improvements in ARTs by enabling the selection of the best embryos. By combining morphological assessment and metabolomics, the selection of high-quality embryos with the potential to result in successful pregnancies may become more accurate and consistent.
Aging is associated with structural and functional changes in the organism that result in the declining of its functioning. Postponed parenthood has renewed the interest in age-related decline of ...testicular function and male fertility. Still, little is known about the molecular mechanisms associated with testicular senescence and related decline of fertility. Here we sought to elucidate the molecular basis of metabolic changes associated with testicular aging and reproductive potential using an NMR-based metabolomics approach. Testicular metabolic profiles of rats from 3 to 24 months-of-age were analysed. An age-associated decrease in most antioxidant metabolites, like betaine, creatine and glutathione was observed. Amino acid content changed as early as 6 months-of-age, with an increase in branched chain and aromatic amino acids, accompanied by decrease of nucleotide synthesis (IMP, CMP, ATP). Testicular content of phospholipid precursors (choline, ethanolamine, myo-inositol, glycerol) increased with advanced age and was accompanied by a decrease in the levels of their phosphorylated products, suggesting compromised spermatogenesis. This is the first metabolomics study of testicular tissue of aged rats and we were able to identify metabolites associated with reproductive maturity from the onset to senescence. Our results provide evidence for an influence of aging on global testicular metabolome, as early as 6 months-of-age, with a profound alteration of several key metabolic pathways associated with the male reproductive potential.
•Testicular metabolome of Wistar rats is profoundly altered with aging.•Aging leads to a decrease in testicular content of most antioxidant metabolites.•Branched chain and aromatic amino acid content increased with aging.•Increase in testicular phospholipid precursors suggests compromised spermatogenesis.•Aging changes key metabolic pathways associated with male reproductive potential.
Obesity, energy balance and spermatogenesis Oliveira, Pedro F; Sousa, Mário; Silva, Branca M ...
Reproduction (Cambridge, England),
06/2017, Letnik:
153, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Obesity has grown to pandemic proportions. It affects an increasing number of children, adolescents and young adults exposed to the silent comorbidities of this disorder for a longer period. ...Infertility has arisen as one important comorbidity associated with the energy dysfunction promoted by obesity. Spermatogenesis is a highly regulated process that is determined by specific energetic requirements. The reproductive potential of males relies on hormonal-dependent and -independent stimuli that control sperm quality. There are conflicting data concerning the impact of male overweight and obesity on sperm quality, as well as on the possible paternal-induced epigenetic trait inheritance of obesity. In addition, it remains a matter of debate whether massive weight loss induced by lifestyle interventions, drugs or bariatric surgery may or may not benefit obese men seeking fatherhood. Herein, we propose to discuss how energy balance may modulate hormonal signalling and sperm quality in overweight and obese men. We also discuss some molecular mechanisms that mediate obesity-related dysfunction in male reproductive system and how paternal obesity may lead to trait inheritance. Finally, we will discuss how lifestyle modifications and sustained weight loss, particularly the loss achieved by bariatric surgery, may revert some of the deleterious effects of obesity in men and their offspring.
The current lifestyle of "western societies" is based on excessive consumption of high-energy diets and physical inactivity. Such behavior has pressured biological systems towards the development of ...metabolic diseases. This increased incidence of metabolic disorders is also accompanied by a decline in male reproductive health, particularly among young males. Male fertility is sensitive to metabolic dysfunctions, such as diabetes mellitus, which disrupt the link between energy metabolism and reproduction. Evidences showed that compromised sperm parameters induced by diabetes are associated with impaired testicular metabolism, suggesting that deficient testicular bioenergetics contributes to a decline in spermatogenesis. Energy metabolism is a well-coordinated process that involves a network of carbohydrate, lipid and protein metabolic pathways. This intricate process is an act of balance between mitochondria and nucleus, governed by metabolic sensors, such as sirtuins. The emerging role of sirtuins in the control of metabolism has been highlighted, specially in cancer metabolism. Little attention has been given to their role in non-cancerous cells that exhibit a "Warburg-like metabolism", such as Sertoli cells. Spermatogenesis is highly dependent on glycolytic metabolism, since the lactate produced by Sertoli cells is the major substrate of germ cells. The regulation of sirtuins in the glycolytic metabolism not only increases their physiological relevance to the testicular environment, but also suggests that these proteins may control male fertility. This review will discuss the recent findings in the role of sirtuins in testicular metabolism and will address the concept that sirtuins can be a potential target to counteract subfertility/infertility promoted by diabetes mellitus.
The lack of effective disease-modifying therapeutics to tackle Alzheimer's disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. ...Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-β (Aβ) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.
Diabetes mellitus type 2 (T2DM) has been associated with alterations in the male reproductive tract, especially in the epididymis. Although it is known that T2DM alters epididymal physiology, ...disturbing mitochondrial function and favoring oxidative stress, the mechanisms remain unknown. Sirtuin 1 (SIRT1), peroxisome proliferators-activated receptor γ coactivator 1α (PGC-1α), and sirtuin 3 (SIRT3) are key regulators of mitochondrial function and inducers of antioxidant defenses. In this study, we hypothesized that the epididymal SIRT1/PGC-1α/SIRT3 axis mediates T2DM-induced epididymis dysfunction by controlling the oxidative profile. Using 7 Goto-Kakizaki (GK) rats (a non-obese model that spontaneously develops T2DM early in life), and 7 age-matched Wistar control rats, we evaluated the protein levels of SIRT1, PGC-1α, and SIRT3, as well as the expression of mitochondrial respiratory complexes. The activities of epididymal glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) were determined, as well as the epididymal antioxidant capacity. We also evaluated protein nitration, carbonylation, and lipid peroxidation in the epididymis. The T2DM rats presented with hyperglycemia and glucose intolerance. Epididymal levels of SIRT1, PGC-1α, and SIRT3 were decreased, as well as the expression of the mitochondrial complexes II, III, and V, in the T2DM rats. We found a significant decrease in the activities of SOD, CAT, and GPx, consistent with the lower antioxidant capacity and higher protein nitration and lipid peroxidation detected in the epididymis of the T2DM rats. In sum, T2DM disrupted the epididymal SIRT1/PGC-1α/SIRT3 pathway, which is associated with a compromised mitochondrial function. This resulted in a decline of the antioxidant defenses and an increased oxidative damage in that tissue, which may be responsible for the impaired male reproductive function observed in diabetic men.
Visceral adipose tissue (VAT) metabolic profiling harbors the potential to disentangle molecular changes underlying obesity-related dysglycemia. In this study, the VAT exometabolome of subjects with ...obesity and different glycemic statuses are analyzed. The subjects (n = 19) are divided into groups according to body mass index and glycemic status: subjects with obesity and euglycemia (Ob+NGT, n = 5), subjects with obesity and pre-diabetes (Ob+Pre-T2D, n = 5), subjects with obesity and type 2 diabetes under metformin treatment (Ob+T2D, n = 5) and subjects without obesity and with euglycemia (Non-Ob, n = 4), used as controls. VATs are incubated in culture media and extracellular metabolite content is determined by proton nuclear magnetic resonance (1H-NMR). Glucose consumption is not different between the groups. Pyruvate and pyroglutamate consumption are significantly lower in all groups of subjects with obesity compared to Non-Ob, and significantly lower in Ob+Pre-T2D as compared to Ob+NGT. In contrast, isoleucine consumption is significantly higher in all groups of subjects with obesity, particularly in Ob+Pre-T2D, compared to Non-Ob. Acetate production is also significantly lower in Ob+Pre-T2D compared to Non-Ob. In sum, the VAT metabolic fingerprint is associated with pre-diabetes and characterized by higher isoleucine consumption, accompanied by lower acetate production and pyruvate and pyroglutamate consumption. We propose that glucose metabolism follows different fates within the VAT, depending on the individuals’ health status.
The permanent exposure to environmental contaminants promoting weight gain (i.e., obesogens) has raised serious health concerns. Evidence suggests that obesogens are one of the leading causes of the ...marked decline in male fertility and are key players in shaping future health outcomes, not only for those who are directly exposed to them, but also for upcoming generations. It has been hypothesized that obesogens affect male fertility. By using an interdisciplinary strategy, combining in silico, in vitro, in vivo and epidemiological findings, this review aims to contribute to the biological understanding of the molecular transformations induced by obesogens that are the basis of male infertility. Such understanding is shaped by the use of Adverse Outcomes Pathways, a new approach that may shift the paradigm of reproductive toxicology, contributing to the improvement of the diagnosis and management of the adverse effects of obesogens in male fertility.
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