Apolipoprotein synthesis in nonalcoholic steatohepatitis.
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.
Charlton
Michael
M
Department of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. charlton.michael@mayo.edu
Sreekumar
Raghavakaimal
R
Rasmussen
Deborah
D
Lindor
Keith
K
Nair
K Sreekumaran
KS
D000328:Adult; D053299:Apolipoprotein B-100; D001053:Apolipoproteins / Q000096:biosynthesis*; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D005234:Fatty Liver / Q000150:complications* / Q000378:metabolism*; D005340:Fibrinogen / Q000032:analysis; D006505:Hepatitis / Q000150:complications* / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D006801:Humans; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D014176:Protein Biosynthesis; D012016:Reference Values; D012709:Serum Albumin / Q000032:analysis
D053299:Apolipoprotein B-100; D001053:Apolipoproteins; D001055:Apolipoproteins B; D001786:Blood Glucose; D006728:Hormones; D012709:Serum Albumin; D005340:Fibrinogen