Apolipoprotein synthesis in nonalcoholic steatohepatitis

Hepatology. 2002 Apr;35(4):898-904. doi: 10.1053/jhep.2002.32527.


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-(13)C] 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Apolipoprotein B-100
  • Apolipoproteins / biosynthesis*
  • Apolipoproteins B / blood
  • Blood Glucose / analysis
  • Fatty Liver / complications*
  • Fatty Liver / metabolism*
  • Fibrinogen / analysis
  • Hepatitis / complications*
  • Hepatitis / metabolism*
  • Hormones / blood
  • Humans
  • Liver / metabolism
  • Middle Aged
  • Protein Biosynthesis
  • Reference Values
  • Serum Albumin / analysis


  • Apolipoprotein B-100
  • Apolipoproteins
  • Apolipoproteins B
  • Blood Glucose
  • Hormones
  • Serum Albumin
  • Fibrinogen