What about non-alcoholic fatty liver disease as a new criterion to define metabolic syndrome?

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 middleto 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?

What is the role of adiponectin in obesity related non-alcoholic fatty liver disease?

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.

Pathogenesis of hepatic steatosis:The link between hypercortisolism and non-alcoholic fatty liver disease

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 chronicinflammation,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.

Exposure to ambient air particulate matter and non-alcoholic fatty liver disease

The present study was designed to alert the public opinion and policy makers on the supposed enhancing effects of exposure to ambient air particulate matter with aerodynamic diameters < 2.5 mm (PM 2.5 ) on non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western countries. For far too long literature data have been fixated on pulmonary diseases and/or cardiovascular disease, as consequence of particulate exposure, ignoring the link between the explosion of obesity with related syndromes such as NAFLD and air pollution, the worst characteristics of nowadays civilization. In order to delineate a clear picture of this major health problem, further studies should investigate whether and at what extent cigarette smoking and exposure to ambient air PM 2.5 impact the natural history of patients with obesity-related NAFLD,i.e. , development of non alcoholic steatohepatitis, disease characterized by a worse prognosis due its progression towards fibrosis and hepatocarcinoma.

Liver-spleen axis: Intersection between immunity, infections and metabolism

Spleen has been considered a neglected organ so far, even though is strictly linked to liver. The spleen plays an important role in the modulation of the immune system and in the maintenance of peripheral tolerance via the clearance of circulating apoptotic cells, the differentiation and activation of T and B cells and production of antibodies in the white pulp. Moreover, splenic macrophages are able to remove bacteria from the blood and protect from sepsis during systemic infections. We review the spleen function and its assessment in humans starting from the description of spleen diseases, ranging from the congenital asplenia to secondary hyposplenism. From the literature data it is clear that obesity in humans affects different compartments of immune system, even thought there are still few data available on the implicated mechamisms. The intent is to enable clinicians to evaluate the newly recognized role of metabolic and endocrine functions of the spleen with special emphasis to obesity and nonalcoholic fatty liver disease in the context of the available literature.Moreover, understanding the spleen function could be important to develop appropriate prevention strategies in order to counteract the pandemia of obesity. In this direction, we suggest spleen longitudinal diameter at ultrasonography, as simple, cheap and largely available tool, be used as new marker for assessing splenic function, in the context of the so-called liver-spleen axis.

Have guidelines addressing physical activity been established in nonalcoholic fatty liver disease?

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.

Hepatic steatosis in overweight/obese females: New screening method for those at risk

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 amino-transferase, blood pressure and the two imaging para-meters, 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 signif icant 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 β 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, β = 0.35, P = 0.01, and by HOMA, β = 0.41, P = 0.0001. Blood pressure was predicted by HOMA values, β = 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%, specif icity 75%; AUROC for diastolic blood pressure 0.70, cut-off 85 mm of Hg, sensibility 54.5%, specif icity 75%). CONCLUSION: As health care costs are skyrocketing, reliable and mainly inexpensive tools are advisable to better defi ne subjects who really need to lose weight.

TNF-α inhibitors and tocilizumab do not influence hepatic steatosis in patients with rheumatoid arthritis

AIM: To investigate the influence, if any, of tumor necrosis factor(TNF)-α inihibitors and Tocilizumab, on hepatic steatosis(HS) in rheumatoid arthritis(RA) patients in the light of the known role of TNF-α and interleukin-6, which are key-cytokines in the pathogenesis of RA, in inducing HS in general population.METHODS: We retrospectively reviewed the clinical charts of 36 RA patients, out of whom 12 had been treated with Methotrexate(MTX), 12 with TNF inhibitors ± MTX and 12 with Tocilizumab ± MTX. The 3 subgroups of patients matched each other for sex, age, body mass index, metabolic syndrome(MS) and other risk factors for atherosclerosis. At baseline and after 12 mo each patient underwent an abdominal ultrasonog-raphy for the assessment of presence of HS and the evaluation of its grade.RESULTS: No difference was detected either in the prevalence of HS or in that of its distinct grades between the 3 groups of patients at baseline. After 12 mo, the HS grade unchanged in 20 patients(7 subjects treated with MTX, 7 with TNF-α inhibitors ± MTX and 6 Tocilizumab ± MTX); increased in 12 patients(4 subjects treated with MTX, 4 TNF-α blockers ± MTX and 4 Tocilizumab ± MTX); decreased in 4(1 treated with MTX, 1 with anti-TNF-α + MTX and 2 with TCZ ± MTX(P = 0.75). No correlation was found between getting remission or low disease activity and the course of either MS or HS.CONCLUSION: We failed to detect any influence of MTX ± TNF-α inhibitors or Tocilizumab in reducing MS and HS. A prospective study is needed to clarify the topic.

Could the improvement of obesity-related co-morbidities depend on modified gut hormones secretion?

Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures- as diets, physical activity, behavior therapy and pharmacotherapy- have been continuously implemented but still have relatively poor long-term success and mainly scarce adherence. Bariatric surgery is to date the most effective long term treatment for morbid obesity and it has been proven to reduce obesity-related co-morbidities, among them nonalcoholic fatty liver disease, and mortality. This article summarizes such variations in gut hormones following the current metabolic surgery procedures. The profile of gut hormonal changes after bariatric surgery represents a strategy for the individuation of the most performing surgical procedures to achieve clinical results. About this topic, experts suggest that the individuation of the crosslink among the gut hormones, microbiome, the obesity and the bariatric surgery could lead to new and more specific therapeutic interventions for severe obesity and its co-morbidities, also non surgical.