Molecular and Physiological Effects of Browning Agents on White Adipocytes from Bone Marrow Mesenchymal Stromal Cells

Two different types of adipose depots can be observed in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). The primary role of WAT is to deposit surplus energy in the form of triglycerides, along with many metabolic and hormonal activities; as thermogenic tissue, BAT has the distinct characteristic of using energy and glucose consumption as a strategy to maintain the core body temperature. Under specific stimuli—such as exercise, cold exposure, and drug treatment—white adipocytes can utilize their extraordinary flexibility to transdifferentiate into brown-like cells, called beige adipocytes, thereby acquiring new morphological and physiological characteristics. For this reason, the process is identified as the ‘browning of WAT’. We evaluated the ability of some drugs, including GW501516, sildenafil, and rosiglitazone, to induce the browning process of adult white adipocytes obtained from differentiated mesenchymal stromal cells (MSCs). In addition, we broadened our investigation by evaluating the potential browning capacity of IRISIN, a myokine that is stimulated by muscular exercises. Our data indicate that IRISIN was effective in promoting the browning of white adipocytes, which acquire increased expression of UCP1, increased mitochondrial mass, and modification in metabolism, as suggested by an increase of mitochondrial oxygen consumption, primarily in presence of glucose as a nutrient. These promising browning agents represent an appealing focus in the therapeutic approaches to counteracting metabolic diseases and their associated obesity

Functional Characteristics and Coping Strategies among Rugby Athletes: A Cluster Analysis Approach

The developing domain of mental health in sports has gained much interest, acknowledging its pivotal role in athlete performance and well-being. The aim of this research is to provide a quantitative description concerning the levels of mental health, physical activity, cognitive fusion, cognitive flexibility, and coping strategies that characterize rugby athletes by using a data-driven approach. A total of 92 rugby athletes took part in this study and filled out a set of self-administered questionnaires. A correlational analysis showed that general well-being was positively associated with years spent playing rugby (r = 0.23) and coping mechanisms (r = 0.29). Athletes’ well-being was also negatively correlated with cognitive inflexibility (r = −0.41) and cognitive fusion (r = −0.39). A k-means cluster analysis identified two unique groups: group 1, characterized by higher levels of psychological well-being, lower levels of physical activity, greater cognitive flexibility, improved coping techniques, and reduced cognitive fusion, and group 2, which exhibits opposite characteristics. The discrepancies observed in psychological characteristics such as coping strategies, cognitive fusion, and cognitive inflexibility highlight their potential impact on the general health of rugby players. To comprehend the complex interplay between psychological and physical elements in rugby athletes, long-term studies with larger samples are crucial

Physical activity has numerous beneficial effects on metabolic and inflammatory processes

Obesity is a long-term multifactorial chronic disease, characterized by energy imbalance, due to an excess of caloric intake compared to energy expenditure and deregulation of other metabolic parameters, as, altered lipid profile, increased insulin resistance and chronic pro-inflammatory state. A healthy lifestyle, characterized by hypocaloric diet and physical activity, is important to reduce a chronic inflammation, oxidative stress and metabolic disorders typical of obesity. It is well known that the chronic inflammation state and oxidative stress are responsible for the aging and development of many diseases, such as cancer. In the light of these evidences, the aim of this study is to analyse body composition, metabolic profile and oxidative stress levels in obese patients subjected to a physical activity program before and after weight loss. We analysed the glycaemic and lipid profile, body composition such as visceral adipose tissue (VAT), fat mass (FM), and the dROMs serum levels via the Fenton's reaction. We found that in obese patients before physical activity intervention there are higher levels in dROMs serum levels, altered glycaemic and lipid profile and body composition compared to obese patients after physical activity intervention. In conclusion, the physical activity has numerous beneficial effects in obesity, modulating not only metabolic profile but also inflammatory and oxidative stress response

Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as "browning" or "beiging". These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs

The Orexin-A serum levels are strongly modulated by physical activity intervention in diabetes mellitus patients

The Orexin-A (hypocretin-1) is a neuropeptide secreted by neurons in the lateral hypothalamus. This protein regulates physiological and behavioural processes that have an essential impact on energy balance and metabolic status, physical activity, blood glucose levels, and food intake. Furthermore, that orexin-A regulates insulin sensitivity, energy expenditure and metabolic rate and is involved in immune processes and then regulate inflammatory response, with an anti-inflammatory action. Diabetes mellitus (T2DM) is a worldwide health problem associated with obesity and sedentary lifestyle. High glycaemic levels and lipid serum profile, low col-HDL, or hypertension and increased body mass index (BMI) are significantly associated with increased T2DM risk and with increased cardiovascular mortality and morbidity in T2DM patients. For these reasons the aim of this study is to evaluate the biochemical and anthropometric parameters, orexin-A levels by ELISA test and western blotting analysis, and inflammatory cytokines levels such as TNF-a, IL-8 and IL-10 by ELISA test in subjects affected by diabetes mellitus following an accurate physical activity program at baseline, after 3 months and after 6 months. We found that there is a ameliorate of many anthropometric and biochemical parameters; furthermore, there is a statistical increase of orexin-A serum levels already after 3 months compared to baseline in T2DM subjects and also there is a strongly modulation in inflammatory cytokines expression. These found indicates that the physical activity has beneficial effects not only on anthropometric and biochemical parameters but also on orexin-A levels, and then on CNS

Effectiveness of antipsychotics in reducing suicidal ideation: Possible physiologic mechanisms

Background: The aim of this study is to evaluate whether any specific antipsychotic regi-men or dosage is effective in managing suicidal ideation in schizophrenia. Four comparisons were conducted between: (1) clozapine and other antipsychotics; (2) long-acting injectable and oral antipsy-chotics; (3) atypical and typical antipsychotics; (4) antipsychotics augmented with antidepressants and antipsychotic treatment without antidepressant augmentation. Methods: We recruited 103 participants diagnosed with schizophrenia spectrum disorders. Participants were followed for at least six months. The Beck Scale for Suicidal Ideation (BSS) was used to assess the severity of suicidal ideation at each visit. We performed a multiple linear regression model controlling for BSS score at study entry and other confounding variables to predict the change in the BSS scores between two visits. Results: Overall, there were 28 subjects treated with clozapine (27.2%), and 21 subjects with depot antipsychotics (20.4%). In our sample, 30 subjects experienced some suicidal ideation at study entry. When considering the entire sample, there was a statistically significant decrease in suicidal ideation severity in the follow-up visit compared to the study entry visit (p = 0.043). Conclusions: To conclude, our preliminary analysis implies that antipsychotics are effective in controlling suicidal ideation in schizophrenia patients, but no difference was found among alternative antipsychotics’ classes or dosages

The beneficial effects of physical activity and weight loss on human colorectal carcinoma cell lines

Recent studies have demonstrated that obesity is a significant risk factor for the development of several malignancies such as cancer. Colorectal cancer is among the most common cancers worldwide and is strong linked to obesity. A healthy lifestyle, characterized by hypocaloric diet and physical activity, is important to reduce a chronic inflammation, oxidative stress and metabolic disorders typical of obesity (Messina et al, 2018; Messina et al, 2017; Messina et al, 2015). It is well known that the chronic inflammation state and oxidative stress are responsible for the aging and development of many diseases, such as cancer. Dysregulation of cytokine’s secretion probably participates in the establishment of cancer in obese patients. The aim of this study is to analyse the effects of sera from obese patients subjected to a physical activity program before and after weight loss on cell viability, apoptosis and oxidative stress in HCT116 carcinoma cell line treated for 24, 48 and 72 hours through MTT test. We analysed the expression of cytokines in HCT116 cells. We found that sera from obese after physical activity intervention compared to treatment with sera from obese patients before physical activity intervention reduce the survival rate of HCT116 cells through induction of apoptosis and oxidative stress. Finally, we found a reduction of mRNA levels corresponding to the pro-inflammatory IL-6 and IL-8 cytokines together with an increase of the anti-inflammatory IL-10 cytokine. We can conclude that the physical activity has numerous beneficial effects also in colorectal cancer cell, indeed the physical activity and weight loss in obese subjects have an inhibitory and anti-inflammatory effects in a short period on carcinoma cell line

A complex network approach reveals pivotal sub-structure of genes linked to Schizophrenia

Research on brain disorders with a strong genetic component and complex heritability, like schizophrenia and autism, has promoted the development of brain transcriptomics. This research field deals with the deep understanding of how gene-gene interactions impact on risk for heritable brain disorders. With this perspective, we developed a novel data-driven strategy for characterizing genetic modules, i.e., clusters, also called community, of strongly interacting genes. The aim is to uncover a pivotal module of genes by gaining biological insight upon them. Our approach combined network topological properties, to highlight the presence of a pivotal community, matchted with information theory, to assess the informativeness of partitions. Shannon entropy of the complex networks based on average betweenness of the nodes is adopted for this purpose. We analyzed the publicly available BrainCloud dataset, containing post-mortem gene expression data and we focused on the Dopamine Receptor D2, encoded by the DRD2 gene. To parse the DRD2 community into sub-structure, we applied and compared four different community detection algorithms. A pivotal DRD2 module emerged for all procedures applied and it represented a considerable reduction, compared with the beginning network size. Dice index 80% for the detected community confirmed the stability of the results, in a wide range of tested parameters. The detected community was also the most informative, as it represented an optimization of the Shannon entropy. Lastly, we verified that the DRD2 was strongly connected to its neighborhood, stronger than any other randomly selected community and more than the Weighted Gene Coexpression Network Analysis (WGCNA) module, commonly considered the standard approach for these studies

Impedance Analysis to Evaluate Nutritional Status in Physiological and Pathological Conditions

: A thorough knowledge of body composition assessment techniques is the cornerstone for initiating a customized nutritional program. The second step is to consider the potential of their application in different physiological and pathological conditions and their effectiveness in the management of a monitoring pathway during dietary interventions. To date, bioimpedance analysis is the most effective and reliable method for assessing body composition due to its advantages in terms of speed of execution, non-invasiveness and low cost. Therefore, this review article aims to analyze the main concepts and application areas of bioimpedance measurement techniques, in particular vector frequency-based analysis (BIVA) systems, in order to assess their validity in both physiological and pathological conditions