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New and more effective nutritional measures are urgently needed for the prevention of obesity. The role of Ca and vitamin D in obesity has been recently implicated. Low Ca intake and low vitamin D status have been linked with an increased risk of obesity in epidemiological studies; however, clinical intervention trials designed to test this association have produced controversial results. The suggested anti-obesity mechanisms of Ca and vitamin D include the regulation of adipocyte death (apoptosis), adipogenesis and lipid metabolism. Dietary Ca has been also shown to increase faecal fat excretion. The potential role of Ca and vitamin D in shifting energy balance towards a more negative state is an area of considerable interest. Ultimately, a review of recent research findings does not allow the reaching of a definitive conclusion that increasing Ca intake and rising vitamin D status will influence fat mass and body weight or decrease the risk of obesity and overweight.

The role of vitamin D in obesity appears to be linked to vitamin D insufficient/deficient status. However, mechanistic understanding of the role of vitamin D in obesity is lacking. We have shown earlier that the vitamin D hormonal form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), induces cell death by apoptosis in mature adipocytes. This effect of the hormone is mediated by the cellular Ca2+ signaling pathway: a sustained increase of intracellular (cytosolic) Ca2+ concentration followed by activation of Ca2+-dependent initiators and effectors of apoptosis. In recent animal studies, we demonstrated that low vitamin D status is observed in diet-induced obesity (DIO). High intake of vitamin D3 in DIO decreased the weight of white adipose tissue and improved biomarkers related to adiposity and Ca2+ regulation. The anti-obesity effect of vitamin D (1,25(OH)2D3) in DIO was determined by the induction of Ca2+-mediated apoptosis in mature adipocytes executed by Ca2+-dependent apoptotic proteases (calpains and caspases). Thus, a high intake of vitamin D in obesity increases vitamin D nutritional status and normalizes vitamin D hormonal status that is accompanied by the reduction of adiposity. Overall, our findings imply that vitamin D may contribute to the prevention of obesity and obesity-related diseases and that the mechanism of the anti-obesity effect of 1,25(OH)2D3 includes induction of Ca2+-mediated apoptosis in adipocytes.

Targeting gut microbiota with synbiotics (probiotic supplements containing prebiotic components) is emerging as a promising intervention in the comprehensive nutritional approach to reducing obesity. Weight loss resulting from low-carbohydrate high-protein diets can be significant but has also been linked to potentially negative health effects due to increased bacterial fermentation of undigested protein within the colon and subsequent changes in gut microbiota composition. Correcting obesity-induced disruption of gut microbiota with synbiotics can be more effective than supplementation with probiotics alone because prebiotic components of synbiotics support the growth and survival of positive bacteria therein. The purpose of this placebo-controlled intervention clinical trial was to evaluate the effects of a synbiotic supplement on the composition, richness and diversity of gut microbiota and associations of microbial species with body composition parameters and biomarkers of obesity in human subjects participating in a weight loss program. The probiotic component of the synbiotic used in the study contained Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium longum, and Bifidobacterium bifidum and the prebiotic component was a galactooligosaccharide mixture. The results showed no statistically significant differences in body composition (body mass, BMI, body fat mass, body fat percentage, body lean mass, and bone mineral content) between the placebo and synbiotic groups at the end of the clinical trial (3-month intervention, 20 human subjects participating in weight loss intervention based on a low-carbohydrate, high-protein, reduced energy diet). Synbiotic supplementation increased the abundance of gut bacteria associated with positive health effects, especially Bifidobacterium and Lactobacillus, and it also appeared to increase the gut microbiota richness. A decreasing trend in the gut microbiota diversity in the placebo and synbiotic groups was observed at the end of trial, which may imply the effect of the high-protein low-carbohydrate diet used in the weight loss program. Regression analysis performed to correlate abundance of species following supplementation with body composition parameters and biomarkers of obesity found an association between a decrease over time in blood glucose and an increase in Lactobacillus abundance, particularly in the synbiotic group. However, the decrease over time in body mass, BMI, waist circumstance, and body fat mass was associated with a decrease in Bifidobacterium abundance. The results obtained support the conclusion that synbiotic supplement used in this clinical trial modulates human gut microbiota by increasing abundance of potentially beneficial microbial species.

The main practical conclusion based on the mechanistic understanding of vitamin D3‘s role as the precursor of the hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is that physiological concentration of this hormone is homeostatically and precisely controlled and that it can be maintained even at “low” and “deficient” concentrations of the substrate, 25(OH)D3, for a long period of time (up to several months) [2,4]. Because production of 25(OH)D3 is not regulated in a homeostatic fashion, a high and sustained intake of vitamin D3 (>4000 IU/d) will increase the concentration of 25(OH)D3 to >50 ng/mL, thus markedly elevating the risk of chronic vitamin D toxicity. Furthermore, “…in the enzymatic reaction producing 1,25(OH)2D3, the substrate, 25(OH)D3, mechanistically functions not as a rate-limiting, but rather as an inhibitory substrate (i.e., high concentrations of 25(OH)D3 in the blood will inhibit production of 1,25(OH)2D3 in kidneys)” [2], and this limits the value for the organism to maintain a high concentration of 25(OH)D3 but safeguards against vitamin D toxicity due to 1,25(OH)2D3. A successful evidence-based health policy for COVID-19 should also rely on mechanistic information causally connecting the policy intervention (e.g., a high-dose vitamin D supplementation) to its outcomes.

Vitamin D and the antioxidant quercetin, are promising agents for improving physical performance because of their possible beneficial effects on muscular strength and cardiorespiratory fitness. The purpose of this study was to determine the effects of increased intakes of vitamin D, quercetin, and their combination on antioxidant status, the steroid hormone regulators of muscle function, and measures of physical performance in apparently healthy male adults engaged in moderate-to-vigorous-intensity exercise training. A total of 40 adult male participants were randomized to either 4,000 IU vitamin D/d, 1,000 mg/d quercetin, vitamin D plus quercetin, or placebo for 8 weeks. Measures of cardiorespiratory fitness and muscle function, blood markers for antioxidant and vitamin D status, and hormones 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and testosterone were measured pre- and postsupplementation. At enrollment, 88.6% of participants were vitamin D sufficient (serum 25-hydroxyvitamin D >50 nmol/L) and had normal serum testosterone levels. Supplementation with vitamin D significantly increased serum 25(OH)D concentration (by 87.3% in the vitamin D group, P<0.001) and was associated with an increasing trend of testosterone concentration. There were no changes in concentration of 1,25(OH)2D3 and markers of antioxidant status associated with vitamin D or quercetin supplementation. No improvements in physical performance measures associated with vitamin D and quercetin supplementation were found. The findings obtained demonstrate that long-term vitamin D and quercetin supplementation, alone or in combination, does not improve physical performance in male adults with adequate vitamin D, testosterone, and antioxidant status.

To evaluate the effects of chronic quercetin supplementation on endurance performance and antioxidant status in long distance runners. We hypothesized that an improved antioxidant status can be associated with enhanced performance. During 6 weeks of supplementation utilizing a double blind, randomized design, young male subjects received quercetin (1000 mg/day) or placebo while maintaining their current training schedules. Following the end of the supplementation period, there was a significant time × supplement interaction for serum malondialdehyde (MDA), an indicator of lipid peroxidation. There were no significant pre- to post-supplement changes in parameter values employed for measuring total antioxidant capacity, superoxide dismutase activity, and protein oxidation (protein carbonyl) in serum. There were also no significant pre- to post-supplement differences in VO2peak, running economy, heart rate, and rating of perceived exertion (RPE) during the 10 km time trial. The findings obtained indicate that there is a relationship between quercetin supplementation and the statistically significant decreasing trend in MDA levels following 6 weeks of supplementation and training. This evidence suggests that quercetin can reduce oxidative stress (lipid peroxidation). However, performance improvements were not significant (as measured by VO2peak, running economy, heart rate, and RPE).

Drosophila melanogaster is a model organism instrumental for numerous biological studies. The compound eye of this insect consists of some eight hundred individual ommatidia or facets, ca. 15 µm in cross-section. Each ommatidium contains eighteen cells including four cone cells secreting the lens material (cornea). High-resolution imaging of the cornea of different insects has demonstrated that each lens is covered by the nipple arrays--small outgrowths of ca. 200 nm in diameter. Here we for the first time utilize atomic force microscopy (AFM) to investigate nipple arrays of the Drosophila lens, achieving an unprecedented visualization of the architecture of these nanostructures. We find by Fourier analysis that the nipple arrays of Drosophila are disordered, and that the seemingly ordered appearance is a consequence of dense packing of the nipples. In contrast, Fourier analysis confirms the visibly ordered nature of the eye microstructures--the individual lenses. This is different in the frizzled mutants of Drosophila, where both Fourier analysis and optical imaging detect disorder in lens packing. AFM reveals intercalations of the lens material between individual lenses in frizzled mutants, providing explanation for this disorder. In contrast, nanostructures of the mutant lens show the same organization as in wild-type flies. Thus, frizzled mutants display abnormal organization of the corneal micro-, but not nano-structures. At the same time, nipples of the mutant flies are shorter than those of the wild-type. We also analyze corneal surface of glossy-appearing eyes overexpressing Wingless--the lipoprotein ligand of Frizzled receptors, and find the catastrophic aberration in nipple arrays, providing experimental evidence in favor of the major anti-reflective function of these insect eye nanostructures. The combination of the easily tractable genetic model organism and robust AFM analysis represents a novel methodology to analyze development and architecture of these surface formations.

Firmly established in astrophysical observations, dark matter evades direct detection in experiments. Axions and axion-like particles are among the leading dark-matter candidates, and numerous attempts to detect them in laboratories have been performed. Here, we propose to advance these efforts substantially, extending the sensitivity for dark-matter axions in the mass range \\((38-54)~\\mu\\)eV down to the axion-photon couplings \\(g_{a\\gamma\\gamma}\\lesssim \\left(10^{-14}-10^{-15}\\right)\\) GeV\\(^{-1}\\), motivated by generic models of Quantum Chromodynamics axion. Single-photon detectors operating at ultra-low temperatures are key elements of the experiment. The projected sensitivity will be reached in one year of data taking with magnetic field of \\((1-10)\\) T, making Cosmological Axion Sarov Haloscope (CASH) the most sensitive haloscope in this mass range.