Adiponectin but not leptin is involved in early hepatic disease in morbidly obese patients

作者:Hindle Anna Katharine; Edwards Claire; Mendonsa Alisha; Rojkind Marcos; McCaffrey Tim; Fu Sidney; Brody Fred*
来源:Surgical Endoscopy and Other Interventional Techniques, 2010, 24(7): 1547-1551.
DOI:10.1007/s00464-009-0808-5

摘要

Pathologic changes in the liver are common in morbidly obese patients, and insulin resistance may potentiate the progression of nonalcoholic steatohepatitis to fibrosis and cirrhosis. This study investigates the impact of leptin and adiponectin in morbidly obese diabetic and nondiabetic patients with regard to histopathologic changes in the liver.
Thirty-seven morbidly obese patients who underwent bariatric surgery with liver biopsies were enrolled in the study. Fourteen were diabetic and 23 were nondiabetic. Intraoperative liver tissue was sent for histopathologic analysis and extraneous intraoperative tissue was snap-frozen in liquid nitrogen. Total RNA was extracted and RNA was reverse transcribed to cDNA. Real-time quantitative PCR was performed to determine relative gene expression levels. The data were analyzed using a logarithmic transformation and normalized by 18S ribosome expression. Student's t test was used for statistical analysis with p a parts per thousand currency sign 0.05 as significant.
Adiponectin expression was downregulated 4.4-fold (p a parts per thousand currency sign 0.05) in liver samples with evidence of inflammation on pathology. When hepatic inflammation was evaluated separately, there were no statistically significant differences in adiponectin levels between the diabetic and nondiabetic patients. However, overall adiponectin levels in hepatic samples of diabetic patients were 3.8-fold higher than those of nondiabetic patients (p a parts per thousand currency sign 0.05). There were no significant differences in leptin levels regardless of hepatic pathology or diabetic status.
This study illustrates that there is a downregulation of adiponectin in morbidly obese patients with inflammatory infiltrates in the liver. Variations in adiponectin levels could be an indicator of disease progression since inflammatory infiltrates are commonly associated with nonalcoholic steatohepatitis (NASH) in morbidly obese patients. Currently, we are using human myofibroblasts derived from livers of morbidly obese people to further investigate the molecular mechanisms involved in the progression of fatty liver to fibrosis and cirrhosis.

  • 出版日期2010-7