Apolipoprotein synthesis in nonalcoholic steatohepatitis
Open Access
- 1 April 2002
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 35 (4), 898-904
- https://doi.org/10.1053/jhep.2002.32527
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.Funding Information
- Public Health Service (RO1 DK 41973, GCRC RR00585)
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