Katarzyna Zgutka

Caloric restriction (CR), defined as a 30–60% decrease in ad libitum food intake without malnutrition, has emerged as one of the most robust non-pharmacological interventions for promoting metabolic health and longevity in various species, including yeast, worms, flies, rodents, and perhaps non-human primates. In addition, CR has been shown to reduce the incidence of age-related disorders (for example, diabetes, cancer, and cardiovascular disorders) in mammals. Among the key organs influenced by CR, the pancreas—particularly the insulin-producing β-cells—plays a central role in maintaining glucose homeostasis and metabolic balance. A growing body of evidence suggests that CR exerts its beneficial effects, at least in part, through the modulation of nutrient-sensing pathways and epigenetic regulators. Sirtuins, a family of NAD⁺-dependent deacetylases and ADP-ribosyltransferases, have gained attention as pivotal molecular mediators of CR. By responding to changes in cellular energy status, sirtuins regulate diverse processes including gene expression, oxidative stress response, mitochondrial function, and autophagy. In the pancreas, sirtuins such as SIRT1, SIRT3, and SIRT6 have been implicated in preserving β-cell function, enhancing insulin secretion, and protecting against metabolic stress and inflammation. This review critically examines current evidence regarding the role of individual sirtuins in mediating the pancreatic response to caloric restriction, with particular emphasis on β-cell physiology, insulin secretion, mitochondrial function, autophagy, oxidative stress, and inflammatory signaling. We further discuss how these molecular mechanisms contribute to systemic metabolic homeostasis and may influence healthy longevity. Importantly, we integrate experimental findings with emerging clinical evidence demonstrating the recovery of β-cell function following dietary energy restriction and identify current controversies, limitations, and key knowledge gaps that should guide future translational research. Collectively, available evidence suggests that sirtuins represent central molecular links between caloric restriction and β-cell adaptation, highlighting their potential as therapeutic targets for preserving pancreatic function and preventing metabolic disease.

Background: Acute exercise induces measurable inflammatory and hematological responses, which may differ according to training status. Methods: Trained soccer players and sedentary controls completed a progressive exercise test until exhaustion. Blood samples were collected at six time points (up to 48 h post-exercise). Gene expression was assessed using real-time PCR, protein concentration via ELISA, and leukocyte, lymphocyte and neutrophil counts through routine hematology. Analyses included between-group comparisons, within-group time effects, and gene–protein correlations. Results: Sedentary individuals showed delayed increases in TNF-α mRNA (p < 0.05), whereas athletes maintained stable levels. Athletes exhibited consistently higher TNFR-1 expression (p < 0.05), while TNFR-2 showed no differences between groups. IL-4 expression was higher in athletes 30 min (p = 0.038) and 24 h after test (p = 0.002), whereas IL-4 protein decreased in sedentary subjects after 6 h (p = 0.009) and 24 h (p = 0.019). IL-4Rα was transiently elevated post-exercise in sedentary individuals and briefly suppressed in athletes (p = 0.041). Hematological responses showed stronger leukocytosis and neutrophilia in sedentary individuals. Conclusions: The temporal inflammatory patterns differed substantially between groups, indicating more efficient resolution dynamics in trained individuals. These findings highlight practical value for monitoring adaptation and recovery.

Background: Caloric restriction (CR) is a dietary intervention based on limiting calories relative to the basic energy needs of the organism, which changes the intensity of metabolism, causes changes in the functioning of the endocrine and sympathetic systems, and influences the expression of genes in muscle, heart, and brain cells. During the use of CR, there is a transition from carbohydrate supply to increased fat metabolism. Fatty acids are more or less susceptible to free radicals, depending on their molecular structure. Oxidation (peroxidation) contributes to the production of metabolites (including hydroxyeicosatetraenoic acid and hydroxyoctadecadienoic acid), some of which are involved in inflammation. Methods: The aim of this study was to evaluate the effects of long-term caloric restriction on the tissue levels of selected fatty acids and fatty acid-derived lipid mediators with pro-inflammatory or anti-inflammatory properties in skeletal muscle and intestinal tissues. The study was carried out on C57BL/6 mice. During the 8-month experiment, the mice in the study group were fed a 30% calorie restricted diet—according to the Every-Other-Day Diet concept. Analyses were performed on intestinal and muscle tissues collected from animals. Fatty acid derivatives were isolated using solid-phase extraction (C-18 columns) columns, and isolation of fatty acids was performed using a modified Folch method. The compounds were analyzed by liquid and gas chromatography. Results: CR induced detectable alterations in both fatty acid profiles and lipid mediator concentrations in a tissue-specific manner. However, most of these changes did not remain statistically significant after multiple testing correction. Conclusions: These findings suggest potential effects of long-term CR on lipid signaling pathways, although the current dataset lacks the statistical power required to draw definitive conclusions. This study highlights the need for further research using larger sample sizes and integrated multiomic approaches to elucidate the molecular mechanisms underlying lipidomic adaptations to prolonged caloric restriction.

According to the World Health Organization (WHO), a healthy lifestyle is defined as a way of living that lowers the risk of becoming seriously ill or dying prematurely. Physical activity, as a well-known contributor to overall health, plays a vital role in supporting such a lifestyle. Exercise induces complex molecular responses that mediate both acute metabolic stress and long-term physiological adaptations. FGF21 (fibroblast growth factor 21) and GDF15 (growth differentiation factor 15) are recognized as metabolic stress markers, while their receptors play critical roles in cellular signaling. However, the differential gene expression patterns of these molecules in trained and untrained individuals following exhaustive exercise remain poorly understood. This study aimed to examine the transcriptional and protein-level responses in trained and untrained individuals performed a treadmill maximal exercise test to voluntary exhaustion. Blood samples were collected at six time points (pre-exercise, immediately post-exercise, and 0.5 h, 6 h, 24 h, and 48 h post-exercise). Gene expression of FGF21, GDF15, FGFR1 (fibroblast growth factor receptors), FGFR3, FGFR4, KLB (β-klotho), and GFRAL (glial cell line-derived neurotrophic factor receptor alpha-like) was analyzed using RT-qPCR, while plasma protein levels of FGF21 and GDF15 were quantified via ELISA. The results obtained were statistically analyzed by using Shapiro–Wilk, Mann–Whitney U, and Wilcoxon tests in Statistica 13 software. Untrained individuals demonstrated significant post-exercise upregulation of FGFR3, FGFR4, KLB, and GFRAL. FGF21 and GDF15 protein levels were consistently lower in trained individuals (p < 0.01), with no significant correlations between gene and protein expression. Trained individuals showed more stable expression of genes, while untrained individuals exhibited transient upregulation of genes after exercise.

Gestational diabetes mellitus (GDM) imposes serious short- and long-term health problems for the mother and her child. An effective therapeutic that can reduce the incidence of GDM and improve long-term outcomes is a major research priority and is very important for public health. Unfortunately, despite numerous studies, the molecular mechanisms underlying GDM are not fully defined and require further study. Chronic low-grade inflammation, oxidative stress, and insulin resistance are central features of pregnancies complicated by GDM. There is evidence of the involvement of sirtuins, which are NAD+-dependent histone deacetylases, in energy metabolism and inflammation. Taking these facts into consideration, the role of sirtuins in the pathomechanism of GDM will be discussed.

Gestational diabetes mellitus is characterised by an insufficient insulin response to hyperglycaemia and the development of insulin resistance. This state has adverse effects on the health outcomes of the mother and child. Existing hyperglycaemia triggers a state of inflammation that involves several tissues, including the placenta. In this study, we analysed the putative pathomechanism of GDM, with special emphasis on the role of chronic, sterile, pro-inflammatory pathways. The expression and regulation of the elements of IL-1β and Toll-like receptor (TLR) pathways in GDM maternal blood plasma, healthy placental explants and a choriocarcinoma cell line (BeWo cell line) stimulated with pro-inflammatory factors was evaluated. Our results indicate elevated expression of the IL-1β and TLR pathways in GDM patients. After stimulation with IL-1β or LPS, the placental explants and BeWo cell line showed increased production of pro-inflammatory IL-6, TNFa and IL-1β together with increased expression of the elements of the signalling pathways. The application of selected inhibitors of NF-ĸB, MAPK and recombinant interleukin 1 receptor antagonist (IL1RA) proved the key involvement of the IL-1β pathway and TLRs in the pathogenesis of GDM. Our results show the possible existence of loops of autocrine stimulation and a possible inflammatory pathomechanism in placentas affected by GDM.

Endothelial progenitor cells (EPCs) are circulating cells of various origins that possess the capacity for renewing and regenerating the endothelial lining of blood vessels. During physical activity, in response to factors such as hypoxia, changes in osmotic pressure, and mechanical forces, endothelial cells undergo intense physiological stress that results in endothelial damage. Circulating EPCs participate in blood vessel repair and vascular healing mainly through paracrine signalling. Furthermore, physical activity may play an important role in mobilising this important cell population. In this narrative review, we summarise the current knowledge on the biology of EPCs, including their characteristics, assessment, and mobilisation in response to both chronic and acute physical activity in healthy individuals.

Background: The positive effects of prolonged every-other-day (EOD) feeding include decreased body weight and prolonged life span, but also changes in liver metabolism and functions. In the present paper, our aim was to examine the expression of adiponectin (ADIPOQ), leptin, and their receptors (ADIPOR1, ADIPOR2, and LEPR) in the liver tissue of EOD-fed mice in comparison to ad libitum (AL)-treated mice. Methods: After 9 months of EOD treatment, liver tissue was harvested and prepared for analysis. RT-PCR, protein semi-quantitative estimation, and cellular immunolocalization was performed. Results: We noted a decreased expression of leptin in the liver tissue of the EOD male mice in comparison to the AL mice on the protein level. ADIPOQ receptor R1 protein expression was decreased in the liver of EOD-fed male mice, while the expression of ADIPOR2 on the protein level was increased in the EOD animals. Conclusions: To the best of our knowledge, this is the first report showing ADIPOQ and leptin immunolocalization in the liver tissue in a dietary regime experiment. Decreases in leptin expression and IL-6 expression in liver tissue and increases in ADIPOR2 expression may be partly responsible for the beneficial effects of EOD treatment in the liver, including the decrease in inflammation. Further studies are needed to establish whether these changes depend on factors like the type of treatment, species, strain, gender, time of treatment, and others.

Diabetes is one of the greatest healthcare problems; it requires an appropriate approach to the patient, especially when it concerns pregnant women. Gestational diabetes mellitus (GDM) is a common metabolic condition in pregnancy that shares many features with type 2 diabetes mellitus (T2DM). T2DM and GDM induce oxidative stress, which activates cellular stress signalling. In addition, the risk of diabetes during pregnancy can lead to various complications for the mother and foetus. It has been shown that physical activity is an important tool to not only treat the negative effects of diabetes but also to prevent its progression or even reverse the changes already made by limiting the inflammatory process. Physical activity has a huge impact on the immune status of an individual. Various studies have shown that regular training sessions cause changes in circulating immune cell levels, cytokine activation, production and secretion and changes in microRNA, all of which have a positive effect on the well-being of the diabetic patient, mother and foetus.