Does leptin play a role in the pathogenesis of human nonalcoholic steatohepatitis?
OBJECTIVE
Obesity is a risk factor for nonalcoholic steatohepatitis (NASH). Leptin plays an important role in the regulation of food intake, body composition, energy expenditure, and body weight. It has been suggested that leptin plays a role in the pathogenesis of NASH; however, adequate studies are lacking. We therefore conducted a study to explore the role of serum leptin in the pathogenesis of human NASH.


METHODS
We measured the levels of serum leptin and its anthropometric, biochemical, metabolic, and histological correlates in a cohort of patients with NASH (n = 26) and well-matched controls (n = 20). Furthermore, we measured the levels of leptin in the serum and hepatic leptin and leptin receptor messenger RNA (mRNA) expression in liver biopsy specimens of patients with NASH (n = 5) and simple steatosis (n = 5).


RESULTS
Serum leptin was not statistically different between patients with NASH and their controls (21 +/- 13 vs 18 +/- 11 ng/ml, respectively, p = 0.5). There was no correlation between serum leptin and hepatic histology, serum transaminases, fasting insulin levels, or a measure of insulin resistance. After adjusting for covariates in a multiple regression analysis, only percent body fat (p = 0.04) and subcutaneous abdominal fat area (p = 0.04) had significant correlation with serum leptin. There was no expression of leptin mRNA in the cell lysate of liver biopsy specimens of subjects with NASH or steatosis. Additionally, the serum leptin levels and the hepatic leptin receptor mRNA expression were not statistically different between patients with NASH and those with simple steatosis.


CONCLUSIONS
These data do not support a direct role for leptin in the pathogenesis of human NASH.
Chalasani
Naga
N
Department of Medicine, Indiana University School of Medicine, WD OPW 2005, 1001 West 10th Street, Indianapolis, IN 46202, USA.
Crabb
David W
DW
Cummings
Oscar W
OW
Kwo
Paul Y
PY
Asghar
Ali
A
Pandya
Prashant K
PK
Considine
Robert V
RV
D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D012044:Regression Analysis; D012307:Risk Factors; D018709:Statistics, Nonparametric
D020738:Leptin