Does Leptin Play a Role in the Pathogenesis of Human Nonalcoholic Steatohepatitis?

Naga Chalasani, David W. Crabb, Oscar W. Cummings, Paul Y. Kwo, Ali Asghar, Prashant K. Pandya, Robert V. Considine

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

OBJECTIVES: 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. CONCLUSION: These data do not support a direct role for leptin in the pathogenesis of human NASH.

Original languageEnglish (US)
Pages (from-to)2771-2776
Number of pages6
JournalAmerican Journal of Gastroenterology
Volume98
Issue number12
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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