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Apolipoprotein synthesis in nonalcoholic steatohepatitis
Open accessAbstract
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.
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Metadata
- Authors
- Charlton, M., Sreekumar, R., Rasmussen, D., Lindor, K., & Nair, S. K.
- Venue
- Hepatology
- Published
- 2002-04
- Volume
- 35
- Issue
- 4
- Pages
- 898-904
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2513800141
- Cited by
- 333
- References
- 0
- FWCI
- 12.60
- Type
- journal article
- Language
- en
- Open access
- bronze
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