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Background and aim There is increasing evidence suggesting that WHO body mass index (BMI) cut-off values are outdated and should not be applied to different population. To overcome misclassifications, direct measurements of percentage body fat (PBF) would be a better tool for preobesity and obesity diagnosis. The aim of this study was to analyze the body composition in a adult population in Centre-South of Italy, by age and gender, and to verify the accordance between BMI and PBF cut-off points for health status classification. Methods The total subject pool cover a total of 4408 participants adults. A completed screening of anthropometry and body composition by Dual X-ray Absorptiometry, (DXA) was assessed on 3.258 subjects. Results Distributions and quantitative reliable estimates of PBF, total body fat and lean, according to gender and age are provided. The prevalence of "at risk" subjects (preobese and obese) was 69% and 85%, for men and women respectively, according to PBF cut-off points. The agreement of BMI and PBF categories resulted low for the total and male population, even scarce for female population (all P≤0.001). The false negative classification of BMI was stronger for women than men and for younger than older subjects. Conclusions Screening for adiposity in subjects with a normal BMI could better identify those at higher risk for cardiometabolic disturbances and cardiovascular mortality. The herein used cut-offs points of PBF, by age and gender, may provide a useful reference in clinical settings and public health services, in particular for the Italian Caucasian population.

Background Although TNF-α blockade is a very effective therapy for psoriasis, not all patients achieve a favorable outcome. The association between IL-6 and psoriasis has been investigated but no papers have focused on the pharmacogenetics of IL-6. Objective To examine whether the G or the C allele, at position -174 in the promoter of IL-6, influences the relationships between body weight, body composition, and therapeutic response to TNF-α blockers in psoriasis. Methods Sixty patients with psoriasis were studied, at baseline and 6-month follow-up after therapy. Assessment of the -174G/C IL-6 polymorphism, Psoriasis Area and Severity Index and Disease Activity Score-28 scores, body weight (kg), BMI, body composition by Dual-energy X-ray absorptiometry, and systemic inflammation was performed. Results Relevant body composition changes occurred after therapy. Normal weight participants showed a greater increase in fat mass than lean mass, compared with obese participants. According to their genotypes, C(+) carriers showed a greater increase in lean mass and fat mass, at the abdominal region, with respect to C(-) carriers. C(+) carriers outweighed C(-) carriers in the group of treatment responders. A higher number of responders were present among normal weight participants, with respect to obese participants. Obesity and the -174G/C IL-6 polymorphism predicted poor response to TNF-α blockers [odds ratio for C(-) carriers, obese: 2.00 (confidence interval: 1.19-3.38; P≤0.05)]. Conclusion Our data show that the G allele of the -174G/C IL-6 polymorphism and obesity can be considered as risk factors for the prognosis and management of psoriasis. This is the first study to suggest the -174G/C IL-6 polymorphism as a novel genetic marker of responsiveness to TNF-α blockers in psoriasis.

Tumor necrosis factor (TNF)-α is a pro-inflammatory cytokine associated with psoriasis pathogenesis. Anti-TNF-α therapies are effective in psoriasis. A significant weight gain has been reported in patients treated with anti-TNF-α agents. The aim of the present study was to evaluate the body composition changes in psoriatic patients receiving anti-TNF-α therapies according with disease phenotype. Forty patients affected with psoriasis were followed up for 24 weeks and divided into two groups: psoriasis vulgaris (PsO) and psoriatic arthritis (PsA). Anthropometric, blood biochemical, body composition parameters, resting metabolic rate, and disease activity indexes were measured at baseline and at week 24. After 24 weeks of anti-TNF-α administration, the disease activity indexes and concentration of inflammatory markers were significantly decreased. Seventy-five percent of PsO and 60% of PsA patients had an increase in body weight. Weight changes correlated with fat mass gain in the PsO group, and with fat and lean mass gain in the PsA group. In the present study, we demonstrated that a blockage of TNF-α bioactivity is related with fat and lean mass gain in both PsO and PsA subjects. The anti-TNF-α therapies could play a key role in the cross talk between adipose tissue and skeletal muscle, mediated by the reduction of TNF-α and interleukin-6 production.

There is growing evidence that interleukin-6 (IL-6) is linked to the regulation of fat mass (FM). Our previous data define the common -174GC IL-6 polymorphism as a marker for 'vulnerable' individuals at risk of age- and obesity-related diseases. An association between -174GC IL-6 polymorphism and weight loss after bariatric surgery has been demonstrated.We investigated the impact of -174GC IL-6 polymorphism on weight loss, body composition, fluid distribution and cardiometabolic changes in obese subjects, after laparoscopic adjustable gastric banding (LAGB) surgery.A total of 40 obese subjects were studied at baseline and at 6 months follow-up after LAGB surgery. Cardiometabolic and genetic assessment of -174GC IL-6 polymorphism, anthropometric, body composition and fluid distribution analysis were performed.After LAGB surgery, significant reductions in weight (Δ%=-11.66 ± 7.78, P0.001), body mass index (P0.001), total and trunk FM (kg, %) (Δ% of total FM=-22.22 ± 12.15, P0.01), bone mineral density (T-score) (P0.001), resting metabolic rate (RMR) (P0.01), and total body water and intracellular water (TBW, ICW) (P0.05) were observed. At baseline, C(-) carriers of IL-6 polymorphism had a significantly higher RMR (P0.05), free FM (kg), but less total and trunk FM (%), higher body cell mass (BCM), content of TBW (L) and ECW (extracellular water)/ICW ratio compared with C(+) carriers (P0.001). After LAGB, C(+) carriers had a significantly stronger reduction of total FM (kg), but lower bone density, compared with C(-) carriers (P0.05).Beyond the relationship between -174GC IL-6 polymorphism and body composition, this study provides first evidence about the association of IL-6 variant with fluid distribution, at baseline, and FM and bone density loss in obese subjects at 6 months follow-up after LAGB surgery. LAGB was less effective if the subjects were carrying risk genotypes, C(-) carriers, for obesity, suggesting a role of genetic variations on bariatric surgery outcomes.

The normal-weight obese (NWO) syndrome was identified in women whose body weight (BW) and BMI are normal but whose fat mass (FM) is30%. In these subjects, an early inflammatory status has been demonstrated. The aim was to verify whether oxidative stress occurs in NWO. Sixty age-matched white Italian women were studied and subdivided as follows: 20 normal-weight individuals (NW) (BMI25 kg/m(2); FM%30%); 20 NWO (BMI25 kg/m(2); FM%30%); 20 preobese-obese (OB) (BMI25 kg/m(2); FM%30%). Anthropometric, body composition (by dual-energy X-ray absorptiometry) variables, plasma levels of some cytokines, reduced glutathione (GSH), lipid hydroperoxide (LOOH), nitric oxide (NO) metabolites (NO(2)(-)/NO(3)(-)), antioxidant nonproteic capacity (ANPC) were measured and compared between groups. Glucose and lipid metabolism parameters were assessed. GSH and NO(2)(-)/NO(3)(-) levels resulted lower in OB and NWO compared to NW (P0.01). LOOH levels resulted higher in OB and NWO (P0.01). ANPC in NWO was lower than NW but higher with respect to OB (P0.01). Correlation analysis revealed strong associations between GSH levels and BW, BMI, FM% (R = -0.45, at least P0.05); waist circumference (W) (R = -0.33, P0.05); FFM% (R = 0.45, P0.01); IL-1α, IL-6, IL-10, IL-15 (R = -0.39, -0.33, -0.36 -0.34, respectively, P0.05); triglycerides (R = -0.416, P0.05). LOOH levels were negatively related to FFM% (R = -0.413, P0.05) and positively to FM%, IL-15, TNF-α, insulin, total cholesterol, low-density lipoprotein cholesterol, and triglycerides (R = 0.408, R = 0.502, R = 0.341, R = 0.412, R = 0.4036, R = 0.405, R = 0.405, respectively, P0.05). The study clearly indicates that NWO, besides being in early inflammatory status, are contextually exposed to an oxidative stress related to metabolic abnormalities occurring in obesity.

Infection with hepatitis C virus (HCV) is still a major public health problem, and the events leading to hepatocyte infection are not yet fully understood. Combining confocal microscopy with biochemical analysis and studies of infection requirements using pharmacological inhibitors and small interfering RNAs, we show here that engagement of CD81 activates the Rho GTPase family members Rac, Rho, and Cdc42 and that the block of these signaling pathways drastically reduces HCV infectivity. Activation of Rho GTPases mediates actin-dependent relocalization of the HCV E2/CD81 complex to cell-cell contact areas where CD81 comes into contact with the tight-junction proteins occludin, ZO-1, and claudin-1, which was recently described as an HCV coreceptor. Finally, we show that CD81 engagement activates the Raf/MEK/ERK signaling cascade and that this pathway affects postentry events of the virus life cycle. In conclusion, we describe a range of cellular events that are manipulated by HCV to coordinate interactions with its multiple coreceptors and to establish productive infections and find that CD81 is a central regulator of these events.

Background/Aims The establishment of HCV replicon systems strongly improved the research on the replication processes but poorly advanced our knowledge on the subcellular localization of the structural glycoproteins, mainly due to their low expression. We sought to verify whether reinforcing E1E2 expression in the context of both HCV genomic and subgenomic replicon from either homologous or heterologous strains leads to formation of supramolecular structures including structural and nonstructural proteins. Methods Robust expression of HCV glycoproteins was achieved by stable expression of E1E2p7 from genotype 1a and 1b. Results In these cells, E1 and E2 triggered the formation of dot-like structures in which they co-localized with core and the nonstructural proteins NS3 and NS5A. Confocal microscopy analyses suggested that accumulation of HCV proteins occurs in an ER-derived subcompartment. Moreover, by labeling de novo-synthesized HCV RNA, we showed that these structures constitute a site of viral RNA synthesis. Conclusions Expression in trans of HCV glycoproteins in the context of replicative viral genome or subgenome generates accumulation of structural and nonstructural viral proteins in peculiar cytoplasmic structures. The simultaneous presence of viral RNA, structural and nonstructural protein suggests that these complexes represent not only sites of HCV replication but also potential places of viral pre-budding.