Involvement of Nuclear Factor Kappa B in High-Fat Diet-Related Pancreatic Fibrosis in Rats

BACKGROUND/AIMS: High-fat diets contribute to pancreatic fibrogenesis, but the pathogenesis remains unclear. This study investigated the role of nuclear factor kappa B (NF-kappaB) in high-fat diet-induced pancreatic fibrosis in rats. METHODS: Male Wistar rats were fed a high-fat diet or standard normal chow for 20 weeks. Pancreatic fibrosis was determined by Sirius red staining. Immunohistochemical staining, reverse transcription-polymerase chain reaction and Western blotting were used to identify NF-kappaB-associated genes or protein expressions. RESULTS: Inflammation, fat deposition, pancreatic stellate cell activation and fibrosis were observed in the pancreases of the high-fat diet group. NF-kappaB subunit p65 (NF-kappaB/p65) expression was localized to the nucleus, and intercellular adhesion molecule 1 (ICAM-1) was over-expressed. Pancreatic gene expression levels of NF-kappaB/p65, ICAM-1 and tumor necrosis factor alpha were all elevated significantly in rats fed a high-fat diet compared with control rats. Western blotting also revealed significantly increased levels of ICAM-1 and nuclear NF-kappaB/p65 in rats fed high-fat diets comparison with control rats. CONCLUSIONS: NF-kappaB is involved in high-fat diet-related pancreatic fibrosis.

A clinical study of abnormal bone metabolism in patients with HBV liver cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the pathogenesis of abnormal bone metabolism in patients with HBV liver cirrhosis.</p><p><b>METHODS</b>NM-300 signal-energy X-ray absorptiometry system was used to measure the bone mineral density (BMD) in 61 liver cirrhosis patients and 30 age-matched healthy controls. The serum levels of 1,25(OH)2D3, parathyroid hormone (PTH), calcitonin (CT), bone gamma-carboxyglutamic acid-containing protein (BGP), IL-1beta, IL-6, tumor necrosis factor (TNF)alpha and urine crosslaps were also detected in these patients.</p><p><b>RESULTS</b>BMD in patients with HBV liver cirrhosis was lower than those of the controls. The serum levels of 1,25(OH)2D3 and BGP in cirrhosis patients were lower than those in the controls, and they were much lower in the osteoporosis (OP) group than in the non-osteoporosis (NOP) group. The PTH and CT were higher significantly in the patients than in the controls. The changes of serum 1,25(OH)2D3 and BGP were correlated with the changes of BMD. The serum levels of IL-1beta, IL-6, TNFalpha and urine crosslaps in cirrhosis patients were higher than those of the controls, and they were much higher in the OP group than in the NOP group. We also found that the serum levels of IL-1beta, IL-6, TNFalpha and urine crosslaps had a negative correlation with BMD.</p><p><b>CONCLUSIONS</b>These data suggest that bone formation is weakened and bone resorption is increased in patients with HBV liver cirrhosis, 1,25(OH)2D3 plays an important role in abnormal bone formation. Elevation of serum IL-1beta, IL-6, TNFalpha can accelerate bone resorption and cause hepatic bone disease (HBD). Taking 1,25(OH)2D3 and reducing the level of IL-1beta, IL-6, TNFalpha may be very important in preventing and treating HBD.</p>