Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis.
Fatty change (steatosis) is the most frequent liver pathology in western countries and is caused by a broad range of disorders such as alcohol abuse and metabolic syndrome. The surface layer of lipid droplets (LDs) contains members of a protein family that share homologous sequences and domains, the so-called PAT proteins, named after their constituents, perilipin, adipophilin, and TIP47. We characterized the LD-associated proteins in normal and diseased liver connected with LD accumulation. Adipophilin and TIP47 are expressed in LDs of vitamin A-storing hepatic stellate cells and additionally in LDs of steatotic hepatocytes. Perilipin, which was thought to be characteristic for LDs of adipocytes and steroidogenic cells, becomes de novo expressed in hepatocytes of human steatotic liver. Perilipin splice variant A was found in human steatotic hepatocytes by biochemical, molecular biological, and immunohistochemical methods. Its association with LDs is different from TIP47 and adipophilin, and depends on size and localization of the LDs, suggesting that the different PAT proteins play specific roles during maturation of LDs.
Straub
Beate Katharina
BK
Department of General Pathology, Institute of Pathology, - Heidelberg, Germany. beate.straub@med.uni-heidelberg.de
Stoeffel
Pamela
P
Heid
Hans
H
Zimbelmann
Ralf
R
Schirmacher
Peter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008820:Mice, Obese; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D000070778:Perilipin-1; D000070780:Perilipin-2; D000070796:Perilipin-3; D010750:Phosphoproteins / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; C038196:PLIN3 protein, human; D010455:Peptides; D000070778:Perilipin-1; D000070780:Perilipin-2; D000070796:Perilipin-3; D010750:Phosphoproteins; C000602983:Plin2 protein, mouse; C523440:Plin3 protein, mouse; D011257:Pregnancy Proteins; D033921:Vesicular Transport Proteins