Repin1 maybe involved in the regulation of cell size and glucose transport in adipocytes.
Replication initiator 1 (Repin1) is highly expressed in liver and adipose tissue and has been suggested as candidate gene for obesity and its related metabolic disorders in congenic and subcongenic rat strains. The cellular localization and function of Repin1 has remained elusive since its discovery in 1990. To characterize the role of Repin1 in adipocyte biology, we used siRNA knockdown technology to reduce the expression of Repin1 by electroporation of semiconfluent 3T3-L1 preadipocytes. Glucose transport, palmitate uptake as well as triglyceride content were measured. In paired samples of human visceral and subcutaneous adipose tissue, we investigated whether Repin1 mRNA expression is related to measures of fat accumulation and adipocyte size. We demonstrate that Repin1 increases during adipogenesis. RNA interference based Repin1 downregulation in mature adipocytes significantly reduces adipocyte size and causes reduced basal, but enhanced insulin stimulated glucose uptake into 3T3-L1 cells. Additionally, knockdown of Repin1 resulted in reduced palmitate uptake and significantly changed the mRNA expression of genes involved lipid droplet formation, adipogenesis, glucose and fatty acid transport. Furthermore, we found significant correlations between Repin1 mRNA expression in human paired visceral and subcutaneous adipose tissue and total body fat mass as well as adipocyte size. We have identified a potential role for Repin1 in the regulation of adipocyte size and expression of glucose transporters GLUT1 and GLUT4 in adipocytes.
Ruschke
Karen
K
Department of Medicine, University of Leipzig, 04103 Leipzig, Germany.
Illes
Monica
M
Kern
Matthias
M
Klöting
Ingrid
I
Fasshauer
Mathias
M
Schön
Michael R
MR
Kosacka
Joanna
J
Fitzl
Günther
G
Kovacs
Peter
P
Stumvoll
Michael
M
Blüher
Matthias
M
Klöting
Nora
N
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D048429:Cell Size; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D016601:RNA-Binding Proteins
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; C404766:REPIN1 protein, human; D016601:RNA-Binding Proteins; C552723:Repin1 protein, mouse; D005947:Glucose