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 indi- ces, 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 ultrasonographic findings of ＂bright liver＂ and/or hyper-transaminasemia of unknown origin and/or increase in T-glutamyl-transpeptidase （T-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 pre- sented a weak negative correlation between Iobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metabolically unhealthy overweight/obese patients （MUOs） was evidenced. HOMA, BMI and uric acid, in that sequence, best predicted serum Bcl-2 concentrations. CONCLUSION： IvlUOs 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.

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.

Pancreatic neuroendocrine tumor with hypoglycemia and elevated insulin-like growth factor II:a case report

Pancreatic neuroendocrine tumors(pNETs)can be associated with different clinical syndromes.Insulinoma is the most common functioning pNET characterized by hypoglycemia and hyperinsulinemia.The authors report a case of a man presenting with hypoglycemia and biochemical features of insulinoma.A pancreatic lesion was found and growth hormone(GH)deficiency was also diagnosed associated with an empty sella present on the pituitary magnetic resonance imaging.The disappearance of hypoglycemia and normalization of GH secretion after surgical resection of the pancreatic lesion,revealed a rare pNET secreting insulin-like growth factor II.