Carmine Finelli

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 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?

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.

Non-Alcoholic Fatty Liver Disease in Young Adult Severely Obese Non-Diabetic Patients in South Italy

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.

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.

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.

Should visceral fat be reduced to increase longevity

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.

Circulating levels of sirtuin 4, a potential marker of oxidative metabolism, related to coronary artery disease in obese patients suffering from NAFLD, with normal or slightly increased liver enzymes.

The present study shows low circulating levels of SIRT4 in obese patients with nonalcoholic fatty liver disease mirroring its reduced mitochondrial expression in an attempt to increase the fat oxidative capacity and then the mitochondrial function in liver and in muscle. SIRT4 modulates the metabolism of free fatty acids reducing their high circulating levels but, unfortunately, increasing ROS production. Great concentration of free fatty acids, released by adipose tissue, coupled with oxidative stress, directly results in endothelial dysfunction, early atherosclerosis, and coronary artery disease risk factor.

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 Cushings syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from Cushings 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 Cushings 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 Cushings syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease.

The absence of polymorphisms in ADRB3, UCP1, PPARγ, and ADIPOQ genes protects morbid obese patients toward insulin resistance

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.331 T>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.331 T>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.

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 (PM2.5) 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 PM2.5 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.