Distinct hypoxic regulation of preadipocyte factor-1 (Pref-1) in preadipocytes and mature adipocytes
| Autor: | Hyunsung Park, Bongju Park, Yunwon Moon, Seongyeol Lee |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Aging medicine.medical_specialty Population Adipose tissue Biology Mice 03 medical and health sciences Cancer stem cell 3T3-L1 Cells Internal medicine Adipocytes medicine Animals Obesity Epigenetics education Molecular Biology education.field_of_study Calcium-Binding Proteins Mesenchymal stem cell Cell Biology Cell Hypoxia 030104 developmental biology Endocrinology Histone Gene Expression Regulation Adipogenesis biology.protein Intercellular Signaling Peptides and Proteins H3K4me3 |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1865:334-342 |
| ISSN: | 0167-4889 |
| Popis: | Preadipocyte factor-1 (Pref-1) is a secretory soluble protein, which exerts pleiotropic effects on maintenance of cancer stem cell characteristics and commitment of mesenchymal stem cell lineages by inhibiting adipogenesis. Observations that obesity renders the microenvironment of adipose tissues hypoxic and that hypoxia inhibits adipogenesis lead us to investigate whether hypoxia increases the expression of anti-adipogenic Pref-1 in preadipocytes, mature adipocytes, and adipose tissues from obese mouse. In 3T3-L1 preadipocytes, hypoxia induces Pref-1 by a hypoxia-inducible factor 1 (HIF-1)-dependent mechanism accompanied by increase in the levels of the active histone mark, acetylated H3K9/14 (H3K9/14Ac). Adipogenesis increased the levels of the heterochromatin histone mark, trimethylated H3K27 (H3K27me3), whereas it decreased the levels of H3K4me3 and H3K9/14Ac euchromatin marks of the mouse Pref-1 promoter. However, differently from preadipocytes, in mature adipocytes hypoxia failed to reverse the repressive epigenetic changes of Pref-1 promoter and to increase its expression. Short term (8 weeks) high fat diet (HFD) increased HIF-1α protein in subcutaneous and epididymal adipose tissues, but did not increase Pref-1 expression. Unlike in 3T3-L1 preadipocytes, HIF-1α did not increase Pref-1 expression in adipose tissues in which mature adipocytes constitute the main population. Interestingly, long term (35 weeks) HFD increased Pref-1 in serum but not in obese adipose tissues. This study suggests that Pref-1 is an endocrine factor which is synergistically increased by obesity and age. |
| Databáze: | OpenAIRE |
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