Nuclear Factor-Kappa B Expression and Acyl-Ghrelin in Egyptian Patients with Non-Alcoholic Fatty Liver

Abstract

BACKGROUND: Ghrelin is a gut hormone with various functions including energy metabolism and inflammation inhibition.Nuclear factor-kappa B (NF-kappaB) participates in the initiation and the progression of inflammation, particularly, the cardiovascular and adipose tissue inflammation. To date the combined role of Ghrelin and NF-kappaB in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is a matter of debate. AIM:To investigate whether acyl ghrelin level and NF-kappaB could interplay a role in lipid metabolism and inflammatory injury in NAFLD. PATIENTS AND METHODS: Ninety three adult participates were included in the study, 30 patients had proved nonalcoholic steatohepatitis (NASH), and 38 patients had simple steatosis, as well 25 healthy subjects, matched for age, gender and Body mass index (BMI) to the patients were included in the study as a healthy control group. Full history and clinical examination, abdominal ultrasonography and liver biopsy were done when indicated. Liver function tests, lipid profile, blood sugar, insulin and C- peptide, fasting insulin, and plasma acyl ghrelin concentrations were measured. Nuclear NF-kB mRNA expression was measured by quantitative RT-PCR. RESULTS: Fasting insulin, insulin C-peptide, HOMA-IR, AST, ALT and g-GT were significantly increased and HDL-C was significantly decreased in NAFLD group compared to control group. In addition, a significant increase in ALT, g-GT, fasting insulin, insulin C peptide and HOMA-IR were detected in the NASH group compared to group of simple steatosis. The plasma levels of Acyl-ghrelin was significantly decreased in NAFLD groups compared to normal control group, the lowest level was detected in NASH group as compared to group of simple steatosis. The expression of NF-kB mRNA was significantly increased in NAFLD groups compared to normal control group and its level was significantly increased in NASH compared to simple steatosis. The NF-kB mRNA was positively correlated with BMI, HOMA-IR, ALT, fasting insulin, insulin C-peptide and liver histopathology and acyl-ghrelin was inversely correlated with BMI, HOMR-IR, ALT, fasting insulin, insulin C peptide and liver histopathology. Both were significantly correlated with HDL-C. CONCLUSION: Acyl ghrelin attenuated NAFLD-induced liver injury through down regulation of NF-kappaB and they are associated with disease progression.nbspFurther large scale studies are recommended to consider ghrelin as promising drug for the prevention and treatment of NAFLD