TY - JOUR
T1 - Apolipoprotein synthesis in nonalcoholic steatohepatitis
AU - Charlton, Michael
AU - Sreekumar, Raghavakaimal
AU - Rasmussen, Deborah
AU - Lindor, Keith
AU - Nair, K. Sreekumaran
N1 - Funding Information:
Abbreviations: NASH, nonalcoholic steatohepatitis; apoB-100, apolipoprotein-100; VLDL, very-low–density lipoprotein; mRNA, messenger RNA; BMI, body mass index; FSR, fractional synthesis rate; FCR, fractional catabolic rate; ASR, absolute synthesis rate. From the Department of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN. Received August 8, 2001; accepted January 22, 2002. Supported in part by Public Health Service grants RO1 DK 41973 and GCRC RR00585. Address reprint requests to: Michael Charlton, M.D., Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, 200 First St., S.W., Rochester, MN 55905. E-mail: charlton.michael@mayo.edu; fax: 507-266-1856. Copyright © 2002 by the American Association for the Study of Liver Diseases. 0270-9139/02/3504-0021$35.00/0 doi:10.1053/jhep.2002.32527
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1053/jhep.2002.32527
DO - 10.1053/jhep.2002.32527
M3 - Article
C2 - 11915037
AN - SCOPUS:0036207720
SN - 0270-9139
VL - 35
SP - 898
EP - 904
JO - Hepatology
JF - Hepatology
IS - 4
ER -