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


CONCLUSIONS
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.
Department of Clinical and Experimental Medicine, Federico II University Medical School of Naples, 5, 80131 Naples, Italy. tarantin@unina.it
Giovanni
G
Tarantino
Francesco
F
Scopacasa
Annamaria
A
Colao
Domenico
D
Capone
Marianna
M
Tarantino
Ernesto
E
Grimaldi
Silvia
S
Savastano
D000293:Adolescent; D000328:Adult; D000886:Anthropometry; D005234:Fatty Liver / Q000097:blood* / Q000473:pathology; D005260:Female; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000097:blood*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood*; D014463:Ultrasonography; D055815:Young Adult
D019253:Proto-Oncogene Proteins c-bcl-2