Hepatic steatosis,low-grade chronic inflammation and hormone/growth factor/adipokine imbalance

Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.

Serum Bcl-2 concentrations in overweight-obese subjects with nonalcoholic fatty liver disease

AIM: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indices, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL)and 41 with nonalcoholic steatohepatitis (NASH).METHODS: Circulating levels of Bcl-2 were detected in 84 patients with ultrasono graphic findings of "bright liver" and/or hyper-transaminasemia of unknown origin and/or increase in γ-glutamyl-transpeptidase (γ-GT)strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups (43 with FL and 41 with NASH). Twenty lean subjects, apparently healthy and young, were chosen as controls.RESULTS: Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein (CRP) concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index (BMI) values (P ≤ 0.0001) but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males (P = 0.0008).γ-GT activity was associated with homeostatic metabolic assessment (HOMA) (P = 0.0003) and with serum ferritin (P = 0.02). Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients presented a weak negative correlation between lobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metaboli-cally unhealthy overweight/obese patients (MUOs) was evidenced. HOMA, BMI and uric acid, in that sequence,best predicted serum Bcl-2 concentrations.CONCLUSION: MUOs could be detected by Bcl-2 levels.By favoring the life span of hepatocytes, and enhancing triglyceride formation, the anti-apoptotic process inhibits free fatty acids toxicity in FL.

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.

Bariatric surgery and diabetes remission: Sleeve gastrectomy or mini-gastric bypass?

AIM:To investigate the weight loss and glycemic control status[blood glucose,hemoglobin A1c(HbA1c)and hypoglycaemic treatment].METHODS:The primary risk factor for type 2 diabetes is obesity,and 90%of all patients with type 2 diabetes are overweight or obese.Although a remarkable effect of bariatric surgery is the profound and durable resolution of type 2 diabetes clinical manifestations,little is known about the difference among various weight loss surgical procedures on diabetes remission.Data from patients referred during a 3-year period(from January2009 to December 2011)to the University of Naples"FedericoⅡ"diagnosed with obesity and diabetes were retrieved from a prospective database.The patients were split into two groups according to the surgical intervention performed[sleeve gastrectomy(SG)and mini-gastric bypass(MGB)].Weight loss and glycemic control status(blood glucose,HbA1c and hypoglycaemic treatment)were evaluated.RESULTS:A total of 53 subjects who underwent sleeve gastrectomy or mini-gastric bypass for obesity and diabetes were screened for the inclusion in this study.Of these,4 subjects were excluded because of surgical complications,7 subjects were omitted because young surgeons conducted the operations and 11 subjects were removed because of the lack of follow-up.Thirtyone obese patients were recruited for this study.A total of 15 subjects underwent SG(48.4%),and 16underwent MGB(51.6%).After adjusting for various clinical and demographic characteristics in a multivariate logistic regression analysis,high hemoglobin A1c was determined to be a negative predictor of diabetes remission at 12 mo(OR=0.366,95%CI:0.152-0.884).Using the same regression model,MGB showed a clear trend toward higher diabetes remission rates relative to SG(OR=3.780,95%CI:0.961-14.872).CONCLUSION:Although our results are encouraging regarding the effectiveness of mini-gastric bypass on diabetes remission,further studies are needed to provide definitive conclusions in selecting the ideal procedure for diabetes remission.

Spleen:A new role ffoorr an old player?

The spleen could be considered a neglected organ.To date,it has been deemed an ancillary organ in portal hypertension or an organ localization in lymphoproliferative diseases,even though it has had significant attention in infectious diseases for some time.Now,it is thought to be central in regulating the immune system,a metabolic asset and involved in endocrine function with regard to nonalcoholic fatty liver disease.The main mechanisms involved in this complex network will be critically discussed in this article.