Apolipoprotein synthesis in nonalcoholic steatohepatitis

Michael Charlton, Raghavakaimal Sreekumar, Deborah Rasmussen, Keith Lindor, K. Sreekumaran Nair

Research output: Contribution to journalArticle

252 Scopus citations

Abstract

The pathophysiology of hepatic steatosis, a prerequisite of nonalcoholic fatty liver disease, is poorly understood. Because very-low-density lipoprotein (VLDL) formation is the chief route of hepatic lipid export, we hypothesized that the synthesis of apoB-100, a rate-determining step in hepatic VLDL formation, may be altered in patients with nonalcoholic steatohepatitis (NASH). This study evaluated the relative synthesis rates of apolipoprotein B-100 (apoB-100) in patients with NASH and in lean and body mass index (BMI)-matched (obese) controls without NASH. A primed continuous infusion of L-[1-13C] leucine was used to measure the absolute synthesis rates (ASR) of apoB-100 and fibrinogen in 7 patients with NASH and compared them with 7 lean and 7 obese (BMI-matched) controls without NASH. The ASRs of fibrinogen and albumin also were measured. The mean ASR of apoB-100 in patients with NASH was lower (31.5 ± 3.4 mg/kg/d) than that of obese (115.2 ± 7.2 mg/kg/d, P < .001) and lean controls (82.4 ± 4.1 mg/kg/d, P = .002). In contrast, the mean ASR of fibrinogen was greater in subjects with NASH than in both control groups. These data indicate that NASH is associated with markedly altered hepatic synthesis of apoB-100. The finding that albumin synthesis was not similarly decreased in patients with NASH shows that the attenuation of apoB-100 synthesis is not on the basis of globally impaired hepatic protein synthesis. In conclusion, because apoB-100 synthesis is a rate-determining step in hepatocyte lipid export, decreased synthesis of this protein may be an important factor in the development of hepatic steatosis, a prerequisite for NASH.

Original languageEnglish (US)
Pages (from-to)898-904
Number of pages7
JournalHepatology
Volume35
Issue number4
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Hepatology

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    Charlton, M., Sreekumar, R., Rasmussen, D., Lindor, K., & Nair, K. S. (2002). Apolipoprotein synthesis in nonalcoholic steatohepatitis. Hepatology, 35(4), 898-904. https://doi.org/10.1053/jhep.2002.32527