Increased Expression of Orexin-A in Patients Affected by Polycystic Kidney Disease.

Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group (p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure (p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications.

Exploring the Interplay between Bone Marrow Stem Cells and Obesity.

Obesity, a complex disorder with rising global prevalence, is a chronic, inflammatory, and multifactorial disease and it is characterized by excessive adipose tissue accumulation and associated comorbidities. Adipose tissue (AT) is an extremely diverse organ. The composition, structure, and functionality of AT are significantly influenced by characteristics specific to everyone, in addition to the variability connected to various tissue types and its location-related heterogeneity. Recent investigation has shed light on the intricate relationship between bone marrow stem cells and obesity, revealing potential mechanisms that contribute to the development and consequences of this condition. Mesenchymal stem cells within the bone marrow, known for their multipotent differentiation capabilities, play a pivotal role in adipogenesis, the process of fat cell formation. In the context of obesity, alterations in the bone marrow microenvironment may influence the differentiation of mesenchymal stem cells towards adipocytes, impacting overall fat storage and metabolic balance. Moreover, bone marrow's role as a crucial component of the immune system adds another layer of complexity to the obesity-bone marrow interplay. This narrative review summarizes the current research findings on the connection between bone marrow stem cells and obesity, highlighting the multifaceted roles of bone marrow in adipogenesis and inflammation.

High frequencies (HF) repetitive transcranial magnetic stimulation (rTMS) increase motor coordination performances in volleyball players.

INTRODUCTION: It is widely demonstrated that high frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has facilitative effects and is therefore capable to inducing changes in motor responses. One of the most investigated areas is the dorsolateral prefrontal cortex (DLPFC) as it plays a special executive attention role in actively preserving access to stimulus representations and objectives in environments with plenty of distraction such as those of team sports. Volleyball is a team sport in which the attention and coordination components are essential for achieving performance. Thus, the aim of this study was to investigate if HF rTMS at DLPFC in volleyball players can improve homolateral motor coordination and cortical excitability. RESULTS: This study was a double-blinded (participant and evaluator) matched-pair experimental design. Twenty right-handed female volleyball players were recruited for the study and were randomly assigned either the active rTMS (n = 10) or the sham stimulation group (n = 10). The stimulation was performed in one session with 10 Hz, 80% of the resting motor threshold (RMT) of the right first dorsal interosseous muscle, 5 s of stimulation, and 15 s of rest, for a total of 1500 pulses. Before and after stimulation, the coordination and the cortical excitability were evaluated. The significant finding of this paper was that HF-rTMS of the DLPFC improved performance in terms of the homolateral interlimb coordination, with a significantly decreased in resting motor threshold and MEP latency of the ipsilateral motor cortex. It seem that HF-rTMS could increase coordination performances when the velocity of the execution is higher (120 bpm and 180 bpm). CONCLUSION: Moreover, in active rTMS group significant differences emerged after stimulation in RMT and in MEP latency, while no differences emerged after stimulation in MEP amplitude. In conclusion we believe that these results may be of great interest to the scientific community and may also have practical implications in the future.

The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line.

The ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assumed to have neuroprotective effects, although the molecular mechanisms responsible for these effects are still unclear. Microglial cell activation plays a key role in the development of neurodegenerative diseases, resulting in the production of several proinflammatory secondary metabolites. The following study aimed to investigate the mechanisms by which BHB determines the activation processes of BV2 microglial cells, such as polarization, cell migration and expression of pro- and anti-inflammatory cytokines, in the absence or in the presence of lipopolysaccharide (LPS) as a proinflammatory stimulus. The results showed that BHB has a neuroprotective effect in BV2 cells, inducing both microglial polarization towards an M2 anti-inflammatory phenotype and reducing migratory capacity following LPS stimulation. Furthermore, BHB significantly reduced expression levels of the proinflammatory cytokine IL-17 and increased levels of the anti-inflammatory cytokine IL-10. From this study, it can be concluded that BHB, and consequently the KD, has a fundamental role in neuroprotection and prevention in neurodegenerative diseases, presenting new therapeutic targets.

Iron and Ferroptosis More than a Suspect: Beyond the Most Common Mechanisms of Neurodegeneration for New Therapeutic Approaches to Cognitive Decline and Dementia.

Neurodegeneration is a multifactorial process that involves multiple mechanisms. Examples of neurodegenerative diseases are Parkinson's disease, multiple sclerosis, Alzheimer's disease, prion diseases such as Creutzfeldt-Jakob's disease, and amyotrophic lateral sclerosis. These are progressive and irreversible pathologies, characterized by neuron vulnerability, loss of structure or function of neurons, and even neuron demise in the brain, leading to clinical, functional, and cognitive dysfunction and movement disorders. However, iron overload can cause neurodegeneration. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative diseases. Uncontrolled oxidation of membrane fatty acids triggers a programmed cell death involving iron, ROS, and ferroptosis, promoting cell death. In Alzheimer's disease, the iron content in the brain is significantly increased in vulnerable regions, resulting in a lack of antioxidant defenses and mitochondrial alterations. Iron interacts with glucose metabolism reciprocally. Overall, iron metabolism and accumulation and ferroptosis play a significant role, particularly in the context of diabetes-induced cognitive decline. Iron chelators improve cognitive performance, meaning that brain iron metabolism control reduces neuronal ferroptosis, promising a novel therapeutic approach to cognitive impairment.

The Effects of Curcumin on Inflammasome: Latest Update.

Curcumin, a traditional Chinese medicine extracted from natural plant rhizomes, has become a candidate drug for the treatment of different diseases due to its anti-inflammatory, anticancer, antioxidant, and antibacterial activities. Curcumin is generally beneficial to improve human health with anti-inflammatory and antioxidative properties as well as antitumor and immunoregulatory properties. Inflammasomes are NLR family, pyrin domain-containing 3 (NLRP3) proteins that are activated in response to a variety of stress signals and that promote the proteolytic conversion of pro-interleukin-1ß and pro-interleukin-18 into active forms, which are central mediators of the inflammatory response; inflammasomes can also induce pyroptosis, a type of cell death. The NLRP3 protein is involved in a variety of inflammatory pathologies, including neurological and autoimmune disorders, lung diseases, atherosclerosis, myocardial infarction, and many others. Different functional foods may have preventive and therapeutic effects in a wide range of pathologies in which inflammasome proteins are activated. In this review, we have focused on curcumin and evidenced its therapeutic potential in inflammatory diseases such as neurodegenerative diseases, respiratory diseases, and arthritis by acting on the inflammasome.

α-Tocopherol Protects Lipopolysaccharide-Activated BV2 Microglia.

Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field of study in modern medicine. Microglia are activated in response to inflammatory stimuli. The pathogenesis of various neurodegenerative diseases is closely related to the constant activation of microglia due to their fundamental role as a mediator of inflammation in the brain environment. α-Tocopherol, also known as vitamin E, is reported to possess potent neuroprotective effects. The goal of this study was to investigate the biological effects of vitamin E on BV2 microglial cells, as a possible neuroprotective and anti-inflammatory agent, following stimulation with lipopolysaccharide (LPS). The results showed that the pre-incubation of microglia with α-tocopherol can guarantee neuroprotective effects during microglial activation induced by LPS. α-Tocopherol preserved the branched morphology typical of microglia in a physiological state. It also reduced the migratory capacity; the production of pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10; and the activation of receptors such as TRL4 and CD40, which modulate the PI3K-Akt signaling pathway. The results of this study require further insights and research, but they present new scenarios for the application of vitamin E as an antioxidant for the purpose of greater neuroprotection in vivo for the prevention of possible neurodegenerative diseases.

Cognitive impairment and type 2 diabetes mellitus: Focus of SGLT2 inhibitors treatment.

Gliflozins are a novel class of oral anti-diabetic drugs, acting as inhibitors of sodium-glucose co-transporters (SGLTs) through the proximal convoluted tubules (PCT) and intestinal epithelium. The sodium-glucose co-transporters 2 (SGLT2) are mainly expressed in S1 and S2 segments of the proximal convoluted tubule in the kidneys. Clinical guidelines recommend their use especially in Type 2 Diabetes mellitus (T2DM) patients with vascular complications and/or heart failure highlighting the importance of sodium-glucose co-transporter 2 inhibitors (SGLT2i) pleiotropic effects. Interestingly, cognitive decline is a widely recognized complication of T2DM and, in addition, to clarify its pathophysiology, there is an urgent need to understand how and if diabetes therapies can control diabetes-related cognitive dysfunction. At the time, although SGLT2 proteins are present in the Central Nervous System (CNS), the SGLT2i effects on cognitive impairments remain partly unknown. In pre-clinical studies, SGLT2i ameliorates cognitive dysfunction in obese and T2DM mice, reducing oxidative stress, neuroinflammation and improving neuronal plasticity and mitochondrial brain pathway. In addition, SGLT2i could bring back mTOR to a physiological state of activation, stopping neurodegenerative diseases' onset or progression. Instead, clinical studies on T2DM-related cognitive dysfunction treated by SGLT2i are much more limited. For these reasons, further studies are needed to better elucidate if SGLT2i therapy can affect T2DM-related cognitive decline. In this scenario, this review aims to summarize the state of knowledge on the role of SGLT2i in T2DM-related cognitive dysfunction and stimulate new clinical trials.

Dietary influence on adiponectin in patients with type 2 diabetes.

BACKGROUND: Here, we evaluate the effects of a diet rich in low-glycaemic index carbohydrates and fibre (CHO/Fibre diet) or monounsaturated fatty acids (MUFA diet), on fasting and postprandial adiponectin concentrations and their relationship with the beneficial effects of the experimental diets on postprandial glucose metabolism and liver fat in type 2 diabetes (T2D). METHODS: Fasting and postprandial adiponectin plasma concentrations were measured before and after dietary interventions in the participants to a randomized controlled trial (NCT01025856), wherein 37 men and 8 women with T2D, aged 35-70 years, followed a CHO/Fibre diet or a MUFA diet for an 8-week period. Hepatic fat content by 1 H NMR and fasting and postprandial plasma glucose and insulin measurements were also available. RESULTS: Fasting adiponectin plasma levels did not change after both diets. Postprandial adiponectin significantly increased after the CHO/fibre diet (9.9 ± 1.6 µg/mL vs. 10.8 ± 2.3 µg/mL; P = .033) but not after the MUFA diet (10.6 ± 1.8 µg/mL vs. 10.6 ± 1.6 µg/mL; P = .935) with a significant difference between changes (P = .035). In the combined CHO/Fibre and MUFA groups, fasting and postprandial adiponectin significantly and inversely correlated with postprandial insulin iAUC at baseline and after intervention, and with liver fat content after intervention. CONCLUSIONS: A diet rich in CHO/Fibre increased postprandial plasma adiponectin significantly more than a MUFA diet in patients with T2D. Independently of diet, adiponectin levels associated with postprandial insulin concentrations. The dietary interventions modulated the relationship between adiponectin and liver fat.

microRNA-377-3p downregulates the oncosuppressor T-cadherin in colorectal adenocarcinoma cells.

Colorectal cancer (CRC) is the second leading cause of death of malignant tumors worldwide. Recent studies point to a role for the adiponectin-receptor axis in colorectal carcinogenesis, and in particular to the oncosuppressive properties of the T-cadherin receptor. In addition, the loss of T-cadherin expression in tumor tissues has been linked to cancer progression and attributed to aberrant methylation of its promoter. Recognizing the pivotal role of microRNAs in CRC, this study explores their possible contribution to the downregulation of T-cadherin. A systematic bioinformatics analysis, restricted by microRNA expression data in the colon or in cultured colorectal cell lines, predicted twelve top-ranking target miRNA sites within the 3' UTR of T-cadherin. Experimental validation analyses based on luciferase reporter constructs and miRNA mimic or miRNA inhibitor transfections toward colorectal adenocarcinoma cell lines indicated that miR-377-3p was able to directly bind to the T-cadherin sequence, and thus downregulating its expression. Given the oncogenic activity of miR-377 and the oncosuppressive activity of T-cadherin in CRC, the regulatory circuit highlighted in this study may add new insights into molecular mechanisms driving colorectal carcinogenesis, and perspectively it could be exploited to identify novel biomarkers and therapeutic targets.

Adiponectin is Associated with Neutrophils to Lymphocyte Ratio in Patients with Chronic Obstructive Pulmonary Disease.

Disproportionate systemic inflammation in chronic obstructive pulmonary disease (COPD) is associated with declining lung functions and comorbidities. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have emerged as valuable markers of the systemic inflammation in COPD. Adiponectin (Acpr30) circulates in serum as complexes of different molecular weight (HMW, MMW, LMW) with multifaceted metabolic and anti-inflammatory properties implicated in airway pathophysiology. We aimed to investigate the association between Acpr30 and its oligomers and the NLR and PLR in COPD patients. Seventy stable COPD patients were enrolled. Acrp30 serum levels and the HMW oligomers as well as hematological parameters and their ratio were evaluated. Both NLR and PLR are associated with lower BMI. Interestingly, total Acpr30 is negatively associated with NLR but not with PLR; after adjusting for age, BMI and FEV1, Acpr30 was independently associated with NLR. Conversely, HMW Acpr30 and HMW/Acpr30 ratio were positively correlated to NLR. The association of Acpr30, HMW Acpr30 and HMW/totalAcpr30 ratio with NLR but not with PLR in COPD patients indicates that Acrp30 oligomerization could represent a biological mechanism interfering with systemic inflammation in COPD. Further studies in larger cohorts of patients are required to confirm these results.

Adiponectin and Leptin Exert Antagonizing Effects on HUVEC Tube Formation and Migration Modulating the Expression of CXCL1, VEGF, MMP-2 and MMP-9.

Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration; after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration; interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel's formation, to candidate them as therapeutic targets.

Molecular mechanisms involved in the positive effects of physical activity on coping with COVID-19.

PURPOSE: Physical activity (PA) represents the first line of defence against diseases characterised by increased inflammation status, such as metabolic and infectious diseases. Conversely, a sedentary lifestyle-associated with obesity, type 2 diabetes and cardiovascular disorders-negatively impacts on general health status, including susceptibility to infections. At a time of a pandemic SARS-CoV2 infection, and in the context of the multiorgan crosstalk (widely accepted as a mechanism participating in the pathophysiology of all organs and systems), we examine the complex interplay mediated by skeletal muscle contraction involving the immune system and how this contributes to control health status and to counteract viral infections. In so doing, we review the molecular mechanisms and expression of molecules modulated by PA, able to provide the proper molecular equipment against viral infections such as the current SARS-CoV2. METHODS: A critical review of the literature was performed to elucidate the molecular mechanisms and mediators induced by PA that potentially impact on viral infections such as SARS-CoV2. RESULTS: We showed the effects mediated by regular moderate PA on viral adverse effects through the regulation of biological processes involving the crosstalk between skeletal muscle, the immune system and adipose tissue. Evidence was provided of the effects mediated by modulation of the expression of inflammation markers. CONCLUSION: A tigth association between PA and reduction in inflammation status allows effective counteracting of SARS-CoV2 infection. It is therefore essential to persuade people to keep active.

Nutritional factors influencing plasma adiponectin levels: results from a randomised controlled study with whole-grain cereals.

Data from intervention studies about the effects of a high intake of whole-grain cereals on adiponectin expression are still inconclusive. We evaluated the effects of whole-grain or refined cereals on fasting and postprandial serum adiponectin in people at high cardiovascular risk. According to a randomised controlled parallel group design, participants with metabolic syndrome were assigned to an isoenergetic diet based on either whole-grain cereal (WGC) or refined cereal (RC) products for 12-weeks. Anthropometric and biochemical measures were taken. Compared to baseline, fasting and postprandial serum adiponectin levels increased after both RC and WGC. In the WGC and RC groups combined, adiponectin concentrations significantly increased after 12-week intervention, and are directly associated with plasma SCFAs and acetate. Only increasing whole-grain cereals may not influence adiponectin levels, which could be modified by a fibre rich, low-fat, low-glycemic index diet, possibly through changes in gut microbiota, as suggested by the relation with SCFAs.Clinical Trials number: NCT00945854.

Adiponectin Role in Neurodegenerative Diseases: Focus on Nutrition Review.

Adiponectin is an adipokine produced by adipose tissue. It has numerous beneficial effects. In particular, it improves metabolic effects and glucose homeostasis, lipid profile, and is involved in the regulation of cytokine profile and immune cell production, having anti-inflammatory and immune-regulatory effects. Adiponectin's role is already known in immune diseases and also in neurodegenerative diseases. Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are a set of diseases of the central nervous system, characterized by a chronic and selective process of neuron cell death, which occurs mainly in relation to oxidative stress and neuroinflammation. Lifestyle is able to influence the development of these diseases. In particular, unhealthy nutrition on gut microbiota, influences its composition and predisposition to develop many diseases such as neurodegenerative diseases, given the importance of the "gut-brain" axis. There is a strong interplay between Adiponectin, gut microbiota, and brain-gut axis. For these reasons, a healthy diet composed of healthy nutrients such as probiotics, prebiotics, polyphenols, can prevent many metabolic and inflammatory diseases such as neurodegenerative diseases and obesity. The special Adiponectin role should be taken into account also, in order to be able to use this component as a therapeutic molecule.

Short-Term Physiological Effects of a Very Low-Calorie Ketogenic Diet: Effects on Adiponectin Levels and Inflammatory States.

Adipose tissue is a multifunctional organ involved in many physiological and metabolic processes through the production of adipokines and, in particular, adiponectin. Caloric restriction is one of the most important strategies against obesity today. The very low-calorie ketogenic diet (VLCKD) represents a type of caloric restriction with very or extremely low daily food energy consumption. This study aimed to investigate the physiological effects of a VLCKD on anthropometric and biochemical parameters such as adiponectin levels, as well as analyzing oligomeric profiles and cytokine serum levels in obese subjects before and after a VLCKD. Twenty obese subjects were enrolled. At baseline and after eight weeks of intervention, anthropometric and biochemical parameters, such as adiponectin levels, were recorded. Our findings showed a significant change in the anthropometric and biochemical parameters of these obese subjects before and after a VLCKD. We found a negative correlation between adiponectin and lipid profile, visceral adipose tissue (VAT), C-reactive protein (CRP), and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which confirmed the important involvement of adiponectin in metabolic and inflammatory diseases. We demonstrated the beneficial short-term effects of a VLCKD not only in the treatment of obesity but also in the establishment of obesity-correlated diseases.

Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work.

BACKGROUND: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.

Adiponectin Expression Is Modulated by Long-Term Physical Activity in Adult Patients Affected by Cystic Fibrosis.

Cystic fibrosis (CF) is a genetic disease characterized by progressive decline of lung function and chronic airway inflammation. Adipose tissue, through adiponectin and leptin, exerts several effects on energy metabolism and inflammatory processes. This study evaluated the levels of adiponectin and leptin in adult healthy subjects, in patients with CF and their correlation with long-term physical activity. CF patients were divided into two groups (sedentary versus active) based on their regular physical activity over 3 years. Anthropometric and serum biochemical profiles of CF patients and controls were evaluated and compared. Total serum adiponectin and leptin levels were measured by ELISA; adiponectin oligomeric profiles were analysed by western blot. Adiponectin levels were significantly higher while leptin levels were lower in patients with CF than in healthy controls. Furthermore, adiponectin was significantly lower in active compared to sedentary CF (p = 0.047), while leptin was slightly increased in active compared to sedentary CF. In addition, C-reactive protein levels were significantly lower in active than in sedentary CF patients (p = 0.048). Interestingly, only in the active group adiponectin levels were inversely correlated with forced expiratory volume (FEV) 1% decrease/year and FEV1% decrease. Moreover, adiponectin levels negatively correlated with lipid profiles. Our findings indicated that regular, long-term physical activity in CF improves respiratory function, metabolism, and inflammation status. These improvements in patients' conditions are associated with immunometabolic processes involving adiponectin, leptin, and C-reactive protein. Therefore, we propose that both adipokines may be a useful biomarker in the evaluation of metabolic and inflammatory status in patients with CF.

Adiponectin as Link Factor between Adipose Tissue and Cancer.

Adipose tissue is a key regulator of energy balance playing an active role in lipid storage as well as in synthesizing several hormones directly involved in the pathogenesis of obesity. Obesity represents a peculiar risk factor for a growing list of cancers and is frequently associated to poor clinical outcome. The mechanism linking obesity and cancer is not completely understood, but, amongst the major players, there are both chronic low-grade inflammation and deregulation of adipokines secretion. In obesity, the adipose tissue is pervaded by an abnormal number of immune cells that create an inflammatory environment supporting tumor cell proliferation and invasion. Adiponectin (APN), the most abundant adipokine, shows anti-inflammatory, anti-proliferative and pro-apoptotic properties. Circulating levels of APN are drastically decreased in obesity, suggesting that APN may represent the link factor between obesity and cancer risk. The present review describes the recent advances on the involvement of APN and its receptors in the etiology of different types of cancer.

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

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.