Hypoxia-inducible factor-3alpha functions as an accelerator of 3T3-L1 adipose differentiation.
Hypoxia-inducible factor (HIF) is a heterodimer composed of HIF-alpha and -beta, and to date, three HIF-alpha subunits, HIF-1alpha, -2alpha, and -3alpha, have been identified. Among these HIF-alpha subunits, HIF-1alpha represses peroxisome proliferator activator gamma2 gene expression and then inhibits adipogenesis, and HIF-2alpha is induced during adipose differentiation and functions as a positive regulator of adipogenesis. We here found that like HIF-2alpha, HIF-3alpha was induced during 3T3-L1 adipose differentiation. Reporter gene analysis revealed that HIF-2alpha enhanced the promoter activity of the 5'-flanking region of the mouse HIF-3alpha gene (nucleotides -2710 to +56), while HIF-1alpha had no substantial effects on the promoter activity. These results suggested that HIF-2alpha, which was induced during adipogenesis, might regulate the HIF-3alpha gene expression. Furthermore, the 5'-deletion analysis revealed that the sequence between -251 and -228 in mouse HIF-3alpha promoter was essential in response to HIF-2alpha. We further examined the effect of ectopic expression of HIF-3alpha in 3T3-L1 cells on adipose differentiation and found that ectopic expression of HIF-3alpha at the early stage of differentiation induced the expression of several kinds of adipocytes-related genes and enhanced adipogenic potential. HIF-3alpha, which is induced by HIF-2alpha, might function as an accelerator of adipogenesis.
Hatanaka
Misaki
M
Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University.
Shimba
Shigeki
S
Sakaue
Motoharu
M
Kondo
Yukihiro
Y
Kagechika
Hiroyuki
H
Kokame
Koichi
K
Miyata
Toshiyuki
T
Hara
Shuntaro
S
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D051379:Mice; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000099162:Endothelial PAS Domain-Containing Protein 1
D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C444643:Hif3a protein, mouse