Rita Polito

Gene molecular analysis and adiponectin expression in professional Water Polo players.

Metabolic Syndrome prevalence has reaching epidemic proportions worldwide. Adiponectin (Acrp30), and in particular its High Molecular Weight (HMW) oligomers, contributes to enhance insulin sensitivity and to reduce inflammation levels. Physical exercise improves bodys biochemical balance and metabolism resulting effective in prevention of metabolic diseases. Whether improvement of metabolic features mediated by physical exercise is associated with changes in Acrp30 serum composition is not yet clarified. In the present study, we investigated total Acrp30 expression, its oligomeric status and genetic variants in adiponectin gene (ACDC) in twenty-two professional Water Polo (WP) Players and 40 age- and sex-matched controls. Anthropometric, metabolic parameters and total Acrp30 were assessed; Acrp30 oligomeric profile was characterized by Western blot as well as by FPLC analysis. ACDC gene was analyzed by direct-sequencing analysis. Significant elevated body mass index, aspartate aminotransferase and lactate dehydrogenase levels and, conversely, significantly lower concentrations of total and cholesterol low density lipoprotein were present in WP players. No significant difference was found in total Acrp30 and/or HMW oligomers. Interestingly, in WP players, a direct relationship between total Acrp30 and monocytes as well as an inverse relationship between total Acrp30 and AST levels were found. ACDC screening revealed previously described SNPs. In conclusion, our study confirms the long-term beneficial effects of high physical training on metabolism and suggests that they are not associated with Acrp30 and/or HMW oligomers changes. Moreover, the correlation of Acrp30 with monocytes in WP athletes could represent a mechanism by which Acrp30 participates in exercise-induced anti-inflammatory functions and/or cardiovascular health.

Total and High Molecular Weight Adiponectin Expression Is Decreased in Patients with Common Variable Immunodeficiency: Correlation with Ig Replacement Therapy

Adiponectin (Acrp30) is an adipokine widely studied for its beneficial metabolic properties. It circulates as low molecular weight (LMW), medium molecular weight (MMW), and high molecular weight (HMW) oligomers. The latter exerts the most potent biological effects. Acrp30 attracted renewed interest with the finding that it was associated with the development and progression of immune disorders. The mechanisms underlying this association and the role of Acrp30 in the pathophysiology of immune-mediated conditions remain unknown. Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by chronic activation of the immune system, impaired antibody production, and imbalanced cytokine production. In the attempt to shed light on the expression of Acrp30 in CVID, we: (a) investigated total Acrp30 and its oligomerization state in CVID patients undergoing maintenance Ig replacement therapy; (b) assessed the effects of Ig replacement therapy on Acrp30 expression in treatment-naïve CVID patients, namely, patients not treated before diagnosis, before and after the first Ig administration; and (c) evaluated the correlation between Acrp30 levels and clinical phenotypes of the disease. As controls, we analyzed healthy subjects and patients affected by a non-immunodeficiency chronic inflammatory demyelinating polyneuropathy (CIDP), before and after Ig infusion. We found that total Acrp30 and HMW oligomers were decreased in CVID but not in CIDP patients versus controls. Moreover, Acrp30 levels were correlated with IgA levels and were associated with two CVID phenotypes, namely, autoimmune cytopenia and enteropathy. Receiver operating characteristic curve analysis indicated that Acrp30 modulation is specific for CVID patients. Acrp30 and HMW levels quickly and dramatically increased after Ig infusion only in eight treatment-naïve CVID patients but not in five CIDP patients. This finding indicates that Ig administration per se is not able to induce an increase of Acrp30, but the specific cellular and/or molecular background proper of CVID seems to be essential. In conclusion, our data indicate that Acrp30 is specifically related to CVID activity. Further studies are required to understand the biological role of Acrp30 and its possible use as disease biomarker in CVID.

Adiponectin profile and Irisin expression in Italian obese children: Association with insulin-resistance

HighlightsTotal Acrp30 and HMW oligomers were lower in obese children than in controls.Irisin levels were significantly higher in obese children than in controls.Irisin levels were inversely correlated to total Acrp30 and HMW oligomer levels. ABSTRACT Adiponectin (Acrp30), its high molecular weight (HMW) oligomers, and Irisin are molecules involved in several metabolic processes. To investigate if these cytokines could represent new metabolic markers, we evaluated the expression of Acrp30 and Irisin in serum of obese children from South Italy affected by different degrees of insulin resistance (IR). The anthropometric and metabolic features were evaluated in 27 obese children versus 13 age‐matched controls. The expression of Acrp30, its pattern and Irisin were investigated by ELISA, western blotting and fast protein liquid chromatography. The HOMA index was significantly higher in obese children versus controls, and metabolic syndrome was more prevalent in obese children with elevated IR versus those with normal HOMA (38% vs 16%). Total Acrp30 and HMW oligomers were significantly lower in obese than in control children, and the difference was more pronounced in children with HOMA >3.4. In control and obese children, total Acrp30 and HMW oligomers were inversely related to HOMA (r‐0.38, p 0.02; r‐0.35, p 0.03). Irisin was significantly higher in obese than in control children, and was inversely correlated with Acrp30 and HMW (r‐0.32, p 0.04; r‐0.39, p 0.01). The inverse correlation of Acpr30 and HMW oligomers with HOMA indicates that Acpr30 is directly involved in IR status. Moreover, the inverse correlation between Irisin and Acrp30 and, more significantly, between Irisin and HMW oligomers suggests that the two cytokines are closely connected. The use of Acrp30, HMW oligomers and Irisin as predictive factors of IR in obese children remains to be further elucidated.

New synthetic AICAR derivatives with enhanced AMPK and ACC activation

Abstract 5-Aminoimidazole-4-carboxamide riboside (AICAR) has an important role in the regulation of the cellular metabolism showing a broad spectrum of therapeutic activities against different metabolic processes. Due to these proven AICAR properties, we have designed, synthesized and tested the biological activity of two ribose-modified AICAR derivatives, named A3 and A4, in comparison to native AICAR and its 5′-phosphorylated counterpart ZMP. Our findings have shown that A3 and A4 derivatives induce the phosphorylation of 5′-AMP activated protein kinase α (AMPKα), which leads to the inhibition of acetyl-CoA carboxylase (ACC), and down-regulate the activity of the extracellular signal-regulated kinases (ERK1/2). Cytotoxicity tests demonstrated that A3 and A4 do not significantly reduce cell viability up to 24 h. Taken together our results indicate that A3 and A4 have a comparable activity to AICAR and ZMP at 0.5 and 1 mM suggesting their potential use in future pharmacological strategies relating to metabolic diseases.

Role of Functional Beverages on Sport Performance and Recovery

Functional beverages represent a palatable and efficient way to hydrate and reintegrate electrolytes, carbohydrates, and other nutrients employed and/or lost during physical training and/or competitions. Bodily hydration during sporting activity is one of the best indicators of health in athletes and can be a limiting factor for sport performance. Indeed, dehydration strongly decreases athletic performance until it is a risk to health. As for other nutrients, each of them is reported to support athletes’ needs both during the physical activity and/or in the post-workout. In this study, we review the current knowledge of macronutrient-enriched functional beverages in sport taking into account the athletes’ health, sports performance, and recovery.

Functional Changes Induced by Orexin A and Adiponectin on the Sympathetic/Parasympathetic Balance

Obesity and lifestyle-related diseases are major problems faced by people in developed nations. Although exercise training prevents the progression of diabetes and obesity, the motivation for exercise is generally low in obese animals and humans. The autonomic nervous system (SNA) plays a crucial role in the regulation of eating behavior. Moreover, the SNA is involved in the body temperature regulation that is strictly related to body weight control, in accordance with the “thermoregulatory hypothesis” of food intake. Some neuronal peptides and hormones, like orexins and adiponectin, are also involved in the regulation of locomotion activity as well as food intake and metabolic rate. Furthermore, adiponectin as well as orexin A are involved in the control of body temperature, food intake and therefore in obesity-related diseases. The aim of this study was to investigate the changes in body temperature (Tc), and heart rate (HR) after an intracerebroventricular (ICV) injection of orexin A and adiponectin in animal model. The results of this study show that the orexin A levels are likely involved in the increase of Tc and HR. It is also clear that there is not a correlation between these parameters and adiponectin levels. Further studies are needed to assess adiponectin actions and outcome in the central nervous system in terms of energy expenditure, body temperature, heart rate and physical activity performance regulation.

Adiponectin and Orexin-A as a Potential Immunity Link Between Adipose Tissue and Central Nervous System

Adipose tissue (AT) is strongly associated with development and progression of immune disorders through adipokines secretion, such as adiponectin. This protein has beneficial energetic properties and is involved in inflammation and immunity processes. Three oligomers of circulating adiponectin with different molecular weight are described: High (HMW), Medium (MMW), and Low (LMW). The HMW is the most biologically active oligomers. On binding to its receptors AdipoR1, AdipoR2, and T-cadherin, adiponectin acts on both innate and acquired immunity. The suppression of NF-κB activation and pro-inflammatory cytokine expression in macrophages is mediated by AdipoR1. AdipoR2 mediates polarization of anti-inflammatory M2 macrophages T-cadherin is essential for the M2 macrophage proliferation. Furthermore, adiponectin reduces T cells responsiveness and B cells lymphopoiesis. The immune system is very sensitive to environmental changes and it is not only interconnected with AT but also with the central nervous system (CNS). Cytokines, which are mediators of the immune system, exercise control over mediators of the CNS. Microglia, which are immunity cells belonging to the macrophage family, are present within the CNS. The nervous system is also involved in immunity through the production of neuropeptides such as orexin-A/hypocretin-1. This neuropeptide is involved in metabolic disorders, inflammation and in the immune response. The relationship between adipokines, immunity, and the nervous system is validated by both the role of orexin-A on fat, food intake, and energy expenditure, as well as by role of adiponectin on the CNS. In this review, we focused on the functions of adiponectin and orexin-A as a potential immunity link between AT and CNS.

Physical activity and sport performance: adiponectin in relation to different physio-pathological status

Adiponectin (Acrp30), and in particular its High Molecular Weight (HMW) oligomers, contributes to enhance insulin sensitivity and to reduce inflammation levels. Physical exercise improves body’s biochemical balance and metabolism resulting effective in the prevention and therapy of metabolic diseases. Whether improvement of metabolic features mediated by physical exercise is associated with changes in Acrp30 serum composition is not yet clarified. In the present study, we investigated total Acrp30 expression and its oligomeric status in two different metabolic status: professional Water Polo (WP) Players and adult patients affected by Cystic Fibrosis (CF) that performed regular physical exercise. CF is an inherited metabolic disease characterized by alterations in lipid and glucidic metabolism. Our results demonstrated significant elevated BMI, AST and LDH levels and, conversely, significantly lower concentrations of total cholesterol and VLD were present in WP players. No significant difference was found in total Acrp30 and/or HMW oligomers. Interestingly, in WP players, a direct relationship between total Acrp30 and monocytes as well as an inverse relationship between total Acrp30 and AST levels were found. ACDC molecular screening revealed previously described SNPs. In CF patients, physical exercise has significant effects on lipid and glycemic metabolism. Indeed, patients that performed exercise are characterized by significant decrease of either VLDL, cholesterol and triglycerides, border-line significant decrease of either total cholesterol/HDL and non-HDL cholesterol/HDL ratio and by trend decrease of total, LDL and non-HDL cholesterol, although not significant. It’s to highlight that physical exercise significantly reduces glycemia and HOMA-IR and increases serum albumin. However, physical exercise does not modify Acrp30 concentrations that, on the other hand, result significantly higher in all CF patients compared to controls. In conclusion, even if peripheral muscle abnormalities and respiratory factors limit exercise in patients with CF, our study indicated that physical activity has beneficial effects on lipid and glycemic metabolism in these patients not associated with Acrp30.

A TRUNCATED β-SPECTRIN (202 kD) ASSOCIATED WITH HS AND ISOLATED SPECTRIN DEFICIENCY 122

Hereditary Spherocytosis (HS) is a common hemolytic anemia characterized by a chronic hemolysis with a broad spectrum of clinical severity. The red cells present a varying degree of surface area deficiency resulting in a spherocytic phenotype and increased osmotic fragility. It is now recognized that this disorders is associated with defects of the erythrocyte membrane skeleton. Spectrin, the most abundant skeletal protein, consistes in two chains, α and β, intertwined in an antiparallele manner to form heterodimers which associate at their head region to form tetramers. This skeletal network plays an essential role in determining the shape and deformability of the red cell.