Hypoxia-inducible factor-2α-dependent hypoxic induction of Wnt10b expression in adipogenic cells.

Abstract

Adipocyte hyperplasia and hypertrophy in obesity can lead to many changes in adipose tissue, such as hypoxia, metabolic dysregulation, and enhanced secretion of cytokines. In this study, hypoxia increased the expression of Wnt10b in both human and mouse adipogenic cells, but not in hypoxia-inducible factor (HIF)-2α-deficient adipogenic cells. Chromatin immunoprecipitation analysis revealed that HIF-2α, but not HIF-1α, bound to the Wnt10b enhancer region as well as upstream of the Wnt1 gene, which is encoded by an antisense strand of the Wnt10b gene. Hypoxia-conditioned medium (H-CM) induced phosphorylation of lipoprotein-receptor-related protein 6 as well as β-catenin-dependent gene expression in normoxic cells, which suggests that H-CM contains canonical Wnt signals. Furthermore, adipogenesis of both human mesenchymal stem cells and mouse preadipocytes was inhibited by H-CM even under normoxic conditions. These results suggest that O2 concentration gradients influence the formation of Wnt ligand gradients, which are involved in the regulation of pluripotency, cell proliferation, and cell differentiation.

• Authors: Young-Kwon Park, Bongju Park, Seongyeol Lee, Kang Choi, Yunwon Moon, Hyunsung Park
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 288 Issue 36 Pg. 26311-26322 (Sep 06 2013) ISSN: 1083-351X [Electronic] United States
• PMID: 23900840 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• HIF1A protein, human
• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• Low Density Lipoprotein Receptor-Related Protein-6
• Proto-Oncogene Proteins
• WNT10B protein, human
• Wnt Proteins
• Wnt10b protein, mouse
• endothelial PAS domain-containing protein 1
• Oxygen

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, metabolism)
• Animals
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
• Cell Differentiation (physiology)
• Cell Hypoxia (physiology)
• Cell Proliferation
• Enhancer Elements, Genetic (physiology)
• Gene Expression Regulation (physiology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Low Density Lipoprotein Receptor-Related Protein-6 (genetics, metabolism)
• Mesenchymal Stem Cells (cytology, metabolism)
• Mice
• Mice, Knockout
• NIH 3T3 Cells
• Oxygen (metabolism)
• Proto-Oncogene Proteins (biosynthesis, genetics)
• Wnt Proteins (biosynthesis, genetics)
• Wnt Signaling Pathway (physiology)