Are hepatic steatosis and carotid intima media thickness associated in obese patients with normal or slightly elevated gamma-glutamyl-transferase?

BACKGROUND: Hepatic steatosis (HS) has been associated with obesity and metabolic syndrome (MS), conditions carrying a high risk of coronary artery disease. We aimed to determine whether HS was an independent factor of atherogenic risk beyond its association with MS and its components. METHODS: We assessed the circulating levels of the heat shock protein-70 (HSP-70), a chaperone involved in inflammation, endoplasmic reticulum stress and apoptosis at liver and endothelial level and the gamma-glutamyl transferase activity (γ-GT) correlating them to carotid intima-media thickness (IMT), along with lipid profile, HOMA, C-reactive protein, fibrinogen, ferritin, adiposity type as well as spleen volume in 52 obese pts with grade 1, 128 with grade 2, and 20 with grade 3 of HS evaluated by sonography. RESULTS: Patients with different grade of HS demonstrated overlapping HSP-70 levels; similarly performed obese subjects regarding IMT. Using multiple regression analysis, IMT was predicted by age, visceral adiposity and by HOMA (ß = 0.50, p < 0.0001, ß = 0.30, p = 0.01 and ß = 0.18, p = 0.048 respectively, while the severity of HS was predicted by visceral and subcutaneous adiposity and HOMA (ß = 0.50, p < 0.0001 and ß = 0.27, p = 0.001 and ß = 0.18, p = 0.024, respectively). CONCLUSION: In our series of patients with normal or mild elevation of γ-GT, the severity of HS does not entail higher IMT, which may be linked to MS stigmata.

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 ultrasonographic 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 metabolically 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.

The contribution of omental adipose tissue to adipokine concentrations in patients with the metabolic syndrome.

PURPOSE: To examine differences in peripheral vascular endothelial growth factor (VEGF), interleukin-6 (IL6) and cortisol concentrations between patients with both visceral obesity and metabolic syndrome, and lean controls. In a subsample of metabolic patients underwent abdominal surgery, the adipokine concentrations were measured in venous blood from the omentum to determine information on some processes of synthesis. METHODS: Forty-two healthy lean controls and 46 overweight-obese patients with central adiposity and stigmata of metabolic syndrome were studied. In a subsample of 11 metabolic patients undergoing non-bariatric surgery, blood samples from omental and peripheral veins were taken intraoperatively to determine VEGF, IL6 and cortisol concentrations. RESULTS: Median levels (range) of peripheral VEGF and IL6 were higher in patients than in controls [31.5 (3-112) pg/mL vs 21.35 (9-41.9) pg/mL (P < 0.05) and 5.50 (1.40-13) pg/mL vs 1.15 (0.3-1) pg/mL (P < 0.0001)]. On the other hand, concentrations of VEGF and IL6 from the omental and peripheral veins were similar in the surgery sub-group. Peripheral cortisol concentrations were not higher in patients than in controls, nor were omental concentrations different from the peripheral. Omental and peripheral VEGF and cortisol values were correlated, whereas no association was found between omental and peripheral IL6. CONCLUSIONS: In the presence of abdominal obesity, VEGF and IL6 concentrations are increased in the systemic circulation. The contribution of visceral adipose tissue to circulating levels of VEGF and IL6 was modest.

The soluble transferrin receptor (sTfR)-ferritin index is a potential predictor of celiac disease in children with refractory iron deficiency anemia.

The soluble transferrin receptor (sTfR) distinguishes iron deficiency anemia from other types of anemia. Refractory iron deficiency anemia is often the onset symptom in malabsorption-induced celiac disease. We evaluated whether sTfR levels distinguish celiac disease-associated iron deficiency anemia from iron deficiency anemia of other origin. To this aim we measured sTfR and ferritin levels and their ratio (the sTfR/ferritin index) and other hematological parameters in 42 anemic children (20 with and 22 without celiac disease) vs. 22 non-anemic children with celiac disease and 31 healthy controls (age range 4-12 years). Hemoglobin parameters, mean cell volume, and serum iron and ferritin levels were decreased to a similar extent in the anemic patients (celiac and non-celiac). The sTfR level in non-anemic celiac patients was similar to that of normal controls (1.7+/-0.35 mg/L), whereas it was significantly increased in non-celiac and celiac anemic patients (2.2+/-0.5 mg/L, p<0.05 and 2.7+/-1.2 mg/L, p<0.001, respectively). The sTfR/ferritin index was also increased more in the anemic celiac patients (mean 4.4, range 1.5-12.0) than in anemic non-celiac children (mean 2.6, range 1.4-4.0) compared with non-anemic children (mean 1.2, range 0.7-2.0). Differences were more pronounced when ferritin was <5 ng/mL. Thus, the sTfR/ferritin index may be a predictive measure in discriminating anemic patients with celiac disease from those without celiac disease.

Effect of paraformaldehyde on platelet size and on measurement of surface IgG.

In many platelet assays, as in measurement of platelet-adherent IgG (PAIgG), platelets are fixed in paraformaldehyde (PFA). To better clarify the effect of PFA on platelet size and on PAIgG measurement we compared PAIgG levels in a series of 40 samples, with or without PFA fixing. We used an ELISA which was set up on unfixed platelets and gave excellent results in terms of linearity (r = 0.923), precision (mean CV = 5%) and correlation with a platelet suspension immunofluorescence test. We found PAIgG values in unfixed platelets were about 10-fold higher than in PFA-fixed (0.411 +/- 0.172 fg/platelet vs. 0.035 +/- 0.019 fg/platelet). This discrepancy could be a consequence of the smaller mean platelet volume (MPV) of washed platelets when fixed in PFA (8.0 +/- 0.8 fl as compared to 10.1 +/- 1.07). This effect of PFA could decrease the amount of binding sites for IgG exposed on the platelet membrane and hence explain the significantly lower PAIgG values observed in fixed platelets. The PAIgG measurements on unfixed platelets from 200 healthy subjects displayed a Gaussian distribution with a mean +/- SD of 0.32 +/- 0.13 fg/platelet, i.e., 1200 +/- 500 molecules/platelet.