title: Lipid in the livers of adolescents with nonalcoholic steatohepatitis: combined effects of pathways on steatosis.
abstract: Fatty liver is a prerequisite for the development of nonalcoholic steatohepatitis (NASH). The homeostasis of hepatic lipid is determined by the dynamic balance of multiple pathways introducing lipids into or removing lipids from hepatocytes. We aim to study the different contributions of major lipid pathways to fat deposition in NASH livers. Expression of the lipid metabolism-related genes was analyzed by microarray and quantitative real-time polymerase chain reaction analysis. The expression levels of genes responsible for the rate-limiting steps of fatty acid uptake (CD36, FABPpm, SLC27A2, and SLC27A5), de novo synthesis (ACACB), oxidation (CPT-1), and very low-density lipoprotein (VLDL) secretion (ApoB) were used to evaluate the relative activity of each pathway. The expression levels for CD36 and CPT-1 were confirmed by Western blot analysis. Fatty acid uptake pathways were up-regulated to a higher degree than other pathways. The de novo synthesis pathway was also up-regulated more than both VLDL secretion and fatty acid oxidation pathways. In contrast to other NASH livers, one NASH liver exhibited lower ApoB and CPT-1 expression levels than normal controls. The increased fatty acid uptake and de novo synthesis were the most common causes for steatosis in NASH patients. In a rare case, impaired VLDL secretion and fatty acid oxidation contributed to the development of steatosis. Our study promises a simple method for the determination of why hepatic steatosis occurs in individual patients. This method may allow specific targeting of therapeutic treatments in individual patients.
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, The State University of New York, Buffalo, NY 14214, USA. lixinzhu@buffalo.edu
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
authors.forename: Susan S
authors.initials: SS
authors.lastname: Baker
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.forename: Meng-Hua
authors.initials: MH
authors.lastname: Tao
authors.forename: Raza
authors.initials: R
authors.lastname: Patel
authors.forename: Norma J
authors.initials: NJ
authors.lastname: Nowak
authors.forename: Robert D
authors.initials: RD
authors.lastname: Baker
mesh_terms: D000293:Adolescent; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000032:analysis; D008079:Lipoproteins, VLDL / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D018955:CD36 Antigens; D008055:Lipids; D008079:Lipoproteins, VLDL; D002334:Carnitine O-Palmitoyltransferase