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Non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnoea syndrome (OSAS) are common conditions, frequently encountered in patients with obesity and/or metabolic syndrome. NAFLD and OSAS are complex diseases that involve an interaction of several intertwined factors. Several lines of evidence lend credence to an immune system derangement in these patients, i.e. the low grade chronic inflammation status, reckoned to be the most important factor in causing and maintaining these two illnesses. Furthermore, it is emphasized the main role of spleen involvement, as a novel mechanism. In this review the contribution of the visceral adiposity in both NAFLD and OSAS is stressed as well as the role of intermittent hypoxia. Finally, a post on the prevention of systemic inflammation is made.Abbreviations: ALT: alanine aminotransferase; BMI: body mass index; CCR2: chemokine (C-C motif) receptor 2; CRP: C-reactive protein; CPAP: continuous positive airway pressure; FFA: free fatty acid; IGF-I: insulin-like growth factor; IR: insulin resistance; IL-6: interleukin-6; IH: intermittent hypoxia; IKK-β: IκB kinase β; LPS: lipopolysaccharide; MCP-1: monocyte chemoattractant protein-1; NAFLD: non-alcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; NEFA: non-esterified fatty acid; NF-κB: nuclear factor-κB; OSAS: obstructive sleep apnoea syndrome; PAI-1: plasminogen activator inhibitor-1; ROS: reactive oxygen species; TNF-α: tumor necrosis factor-α; T2D: type 2 diabetes.

Several epidemiologic studies have implicated visceral fat as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and death. Utilizing novel models of visceral obesity, numerous studies have demonstrated that the relationship between visceral fat and longevity is causal while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. Specific recommended intake levels vary based on a number of factors, including current weight, activity levels, and weight loss goals. It is discussed the need of reducing the visceral fat as a potential treatment strategy to prevent or delay age-related diseases and to increase longevity.

The current Western diet figures centrally in the pathogenesis of several chronic diseases such as obesity, type 2 diabetes, cardiovascular disease and the emerging major health problem nonalcoholic fatty liver disease, all of them negatively impacting on life expectancy. This type of diet is represented by a high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of fructose. On the contrary, a simplified way of eating healthily by excluding highly-processed foods, is presumed to be the Paleolithic diet (a diet based on vegetables, fruits, nuts, roots, meat, organ meats) which improves insulin resistance, ameliorates dyslipidemia, reduces hypertension and may reduce the risk of age-related diseases. The diet is the foundation of the treatment of obesity- and type 2 diabetes-related nonalcoholic fatty liver disease and a diet similar to those of pre-agricultural societies may be an effective option. To lend sufficient credence to this type of diet, well-designed studies are needed.

Background: The current increase of obesity and metabolic syndrome (MS) focuses attention on bisphenol-A (BPA), "obesogen" endocrine disruptor, main plastic component. Aim was to verify the role of BPA in metabolic alterations, insulin resistance, low grade inflammation and visceral obesity. Methods: A cross-sectional study was performed in 76 out of 139 environmentally exposed adult males, unselected Caucasian subjects, enrolled by routine health survey at the "Federico II" University of Naples outpatient facilities. BPA plasma levels (ELISA), metabolic risk factors, homeostasis model assessment of insulin resistance index, plasma monocyte chemoattractant protein 1, interleukin-6 (IL-6) and tumor necrosis factor-alpha were performed. Clinical and biochemical parameters have been compared with BPA and pro-inflammatory cytokines levels. Results: In total 24 subjects out of 76 (32%) presented with waist circumference (WC) >102 cm, 36 (47%) had impaired fasting glucose and 24 (32%) subjects had insulin resistance [11 out 52 (21%) with WC ≤102 cm and 13 out of 24 with WC >102 cm (54%), χ(2) 6.825, p = 0.009]. BPA and pro-inflammatory cytokine levels were significantly higher in subjects with visceral adiposity (WC > 102 cm). BPA correlated with WC, triglycerides, glucose homeostasis and inflammatory markers. At the multivariate analysis WC and IL-6 remained the main predictors of BPA. Conclusions: Detectable BPA plasma levels have been found also in our population. The strictly association between BPA and WC, components of MS, and inflammatory markers, further supports the BPA role in visceral obesity-related low grade chronic inflammation.

Background Non-Alcoholic Fatty Liver Disease (NAFLD) is a distinct coronary artery disease (CAD) risk factor. The atherosclerotic process predisposing to CAD includes altered lipid profile and inflammatory processes. The available evidence suggests that increased circulating levels of eotaxin, an eosinophil chemoattractant cytokine implicated in allergic responses, are detected in the serum of patients with CAD. Relationships were sought between serum eotaxin on the one hand, and intima-media thickness--an early predictor of the atherosclerotic process, hepatic steatosis, arterial blood pressure values, as well as inflammation/immune markers and angiogenetic factors--on the other. Methods Eighty obese patients with NAFLD, diagnosed at ultrasonography, without evident cytolysis, formed our study population. Anthropometric measures, metabolic profile, serum concentrations of interleukin-1β, C-reactive protein, interleukin-6, fibrinogen, ferritin, TNF-α, spleen size, vascular endothelial growth factor, platelet-derived growth factor-BB and heat shock protein-70 were evaluated. Results Serum eotaxin concentrations were distinctly associated with TNF α, IL-6, IL-1β, VEGF and PDGF-BB levels but not with CRP, fibrinogen, heat shock protein-70 or spleen size. Among the metabolic and anthropometric parameters, a significant predictive power emerged when comparing eotaxin to insulin resistance, expressed as HOMA. NAFLD was distinctly associated with HOMA (P = 0.0005). Intima-media thickness was well predicted by both eotaxin levels and severity of NAFLD at ultrasonography, although no relation was detected between these last two variables. Discussion and conclusion A role for insulin resistance in mediating the interplay between eotaxin and other inflammation/immune parameters could be evidenced in the induction/maintenance of atherosclerosis of obese patients with NAFLD.

Numerous epidemiologic studies have implicated abdominal obesity as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and its further expression, i.e., nonalcoholic fatty liver disease and death. Using novel models of visceral obesity, several studies have demonstrated that the relationship between visceral fat and longevity is causal, while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. The need of reducing the visceral fat to improve survival, mainly taking into account the strict link between nonalcoholic fatty liver disease and the coronary artery disease is discussed.

The purpose of this review was to highlight, in relation to the currently accepted pathophysiology of non-alcoholic fatty liver disease (NAFLD), the known exercise habits of patients with NAFLD and to detail the benefits of lifestyle modification with exercise (and/or physical activity) on parameters of metabolic syndrome. More rigorous, controlled studies of longer duration and defined histopathological end-points comparing exercise alone and other treatment are needed before better, evidence-based physical activity modification guidelines can be established, since several questions remain unanswered.

Non-alcoholic fatty liver disease (NAFLD) is currently not a component of the diagnostic criteria for metabolic syndrome (MetS); however, the development of NAFLD has some common mechanisms with the development of MetS, as they share the pathophysiologic basis of insulin resistance. It is also recognized that NAFLD is the hepatic manifestation of MetS. To define MetS, the presence of at least three of the proposed criteria is required, and sometimes it is sufficient to have only one laboratory value, modified by diet or drugs, for the classification of MetS. Ultrasonographically-detected NAFLD (US-NAFLD) is more stable, only changing during the middle- to long-term. Although controversies over MetS continue, and considering that abdominal ultrasonography for diagnosing NAFLD has high specificity and guidelines to modify the natural course of NAFLD by diet composition or lifestyle have not yet been established, why should we not introduce US-NAFLD as a new criterion to define MetS?

Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries. Insulin resistance is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of insulin resistance or obesity. Adiponectin is the most abundant adipose-specific adipokine. There is evidence that adiponectin decreases hepatic and systematic insulin resistance, and attenuates liver inflammation and fibrosis. Adiponectin generally predicts steatosis grade and the severity of NAFLD; however, to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be addressed. Although there is no proven pharmacotherapy for the treatment of NAFLD, recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications. In this adiponectin-focused review, the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically.

AIM: To identify which parameters could help to distinguish the "metabolically benign obesity", which is not accompanied by insulin resistance (IR) and early atherosclerosis. METHODS: Eighty two of 124 overweight/obese females formed the study population, which was divided into two groups (52 and 30 subjects, respectively) with and without IR according to a HO meostatic Metabolic Assessment (HOMA) cut-off of 2, and were studied in a cross-sectional manner. The main outcome measures were waist circumference, serum uric acid, high-density lipoprotein-cholesterol and triglycerides, alanine aminotransferase, blood pressure and the two imaging parameters, hepatic steatosis and longitudinal diameter of the spleen, which were measured in relation to the presence/absence of IR. RESULTS: A variable grade of visceral obesity was observed in all subjects with the exception of three. Obesity of a severe grade was represented more in the group of IR individuals (P = 0.01). Hepatic steatosis, revealed at ultrasound, was more pronounced in IR than in non-IR subjects (P = 0.005). The two groups also demonstrated a clear difference in longitudinal spleen diameter and blood pressure, with raised and significant values in the IR group. Metabolic syndrome was frequent in the IR group, and was not modified when adjusted for menopause (P = 0.001). At linear regression, the beta values of waist circumference and body mass index predicting HOMA were 0.295, P = 0.007 and 0.41, P = 0.0001, respectively. Measures of spleen longitudinal diameter were well predicted by body mass index (BMI) values, beta = 0.35, P = 0.01, and by HOMA, beta = 0.41, P = 0.0001. Blood pressure was predicted by HOMA values, beta = 0.39, P = 0.0001). HOMA and hepatic steatosis were highly associated (rho = 0.34, P = 0.002). Interestingly, IR patients were almost twice as likely to have hepatic steatosis as non-IR patients. Among the MS criteria, blood pressure was very accurate in identifying the presence of IR (AUROC for systolic blood pressure 0.66, cut-off 125 mm of Hg, sensibility 64%, specificity 75%; AUROC for diastolic blood pressure 0.70, cut-off 85 mm of Hg, sensibility 54.5%, specificity 75%). CONCLUSION: As health care costs are skyrocketing, reliable and mainly inexpensive tools are advisable to better define subjects who really need to lose weight.

Background/Aims: In the absence of other causes, obesity increases the risk of liver disease. We evaluated the prevalence and degree of metabolic and hepatic abnormalities associated with non-alcoholic fatty liver disease (NAFLD) in type II–III obesity in a metropolitan area of South Italy. Methods: 187 (81 M, 106 F) young adult non-diabetic obese patients, age range 18–50 years (mean 31.9 ± 8.8), body mass index (BMI) ≧30 (mean 47.5 ± 9.6), consecutively admitted from January 2000 to April 2003 to the Obesity Outpatients Clinic entered into the study. Patients were divided into two groups: (1) BMI 30.0–39.9, and (2) BMI≧40. Ultrasound detected liver steatosis was classified as: (I) mild; (II) moderate, and (III) severe. Results: All patients, except 4, showed a variable degree of steatosis: mild was more frequent among females, severe steatosis present only in grade III obesi ty, with higher prevalence in males than in females (p < 0.001). Mean serum transaminases, in particular alanine aminotrasferase (ALT), increased according to BMI and degree of steatosis. Homeostasis Model Assessment (HOMA) index, ferritin and fibrinogen levels increased with BMI, particularly in severe steatosis. In group 2, patients with BMI≧40 showed a positive correlation between ferritin, aspartate aminotransferase (AST) (r = 0.46, p < 0.018), ALT (r = 0.41, p < 0.036) and gamma-glutamyltransferase (γGT) (r = 0.51, p < 0.007), between serum triglycerides (TG) and AST (r = 0.28, p < 0.036), ALT (r = 0.30, p < 0.02) and between HOMA and ALT (r = 0.30, p < 0.03) and γGT (r = 0.35, p < 0.012). In group 2 patients with severe steatosis the prevalence of metabolic syndrome according to Adult Treatment Panel III (ATP III) was 40%. Conclusion: These data suggest that, in young adult non-diabetic grade III obese patients, fatty liver is always present and strictly related to insulin resistance which, in the presence of severe liver steatosis, is also related to serum ferritin.

Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of patients with Cushing’s syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from Cushing’s syndrome - a condition characterized by profound metabolic changes - present low prevalence of hepatic steatosis, the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome. They hypothesize that this low prevalence of fat accumulation in the liver of patients with Cushing’s syndrome could result from the inhibition of the so-called low-grade chronic-inflammation, mainly mediated by Interleukin 6, due to an excess of cortisol, a hormone characterized by an anti-inflammatory effect. The Cushing’s syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease.

Background and aims: The insulin resistance (IR) is a major metabolic impairment in severe obesity, a multifactorial disease in which the importance of the effect of single nucleotide polymorphisms (SNP) associations in different rather than individual genes was established. The aim of this study was to test the predictive value of presence/absence of polymorphisms/variants in β3-adrenergic receptor (ADRB3), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ(PPARγ), and adiponectin (ADIPOQ) genes in diagnosing the IR in obesity. Subjects and methods: We studied 112 (40 males, 72 females) severely obese (body mass index: 48.5±7.5 kg/m2) subjects recruited from the outpatient obesity clinic of Federico II University Hospital in Naples. Genomic DNA was extracted from peripheral leukocytes with a commercial kit. The gene polymorphisms Trp64Arg in ADRB3, -3826 A>G in UCP1, Pro12Ala in PPARγ, and c.268G>A, c.331T>C, and c.334C>T in ADIPOQ were characterized by TaqMan assay or by direct sequencing (ADIPOQ). Results and conclusion: Our results demonstrate that -3826A>G UCP1 polymorphism is associated with IR in morbid obesity. Further, the lack of any polymorphisms, Trp64Arg in ADRB3 and/or -3826 A>G in UCP1 and/or Pro12Ala in PPARγ and/or c.268G>A, c.331T>C and c.334C>T in ADIPOQ, appears a useful prognostic factor (NPV=100%) toward the IR onset in these obese patients representing a further parameter for an earlier and appropriate therapy. ©2012, Editrice Kurtis.