| Autor: |
Jisu Oh, Amy E. Riek, Kevin T. Bauerle, Adriana Dusso, Kyle P. McNerney, Ruteja A. Barve, Isra Darwech, Jennifer Sprague, Clare Moynihan, Rong M Zhang, Ting Wang, Xiaoyun Xing, Daofeng Li, Richard D. Head, Monika Bambouskova, Marguerite Mrad, Alejandro Collins, Mark S. Sands, Carlos Bernal-Mizrachi |
| Rok vydání: |
2022 |
| Popis: |
Environmental factors may alter the fetal genome to cause metabolic diseases. It is unknown whether embryonic immune cell programming impacts the risk of type 2 diabetes in later life. We demonstrate that transplantation of fetal hematopoietic stem cells (HSCs) made vitamin D deficient in utero induces diabetes in vitamin D-sufficient mice. Vitamin D deficiency epigenetically suppresses Jarid2 expression and activates the Mef2/PGC1a pathway in HSCs, which persists in recipient bone marrow, resulting in adipose macrophage infiltration. These macrophages secrete miR106-5p, which promotes adipose insulin resistance by repressing PIK3 catalytic subunit alpha and AKT signaling. Vitamin D-deficient monocytes from human cord blood have comparable Jarid2/Mef2/PGC1a expression changes and secrete miR-106b-5p, causing adipocyte insulin resistance. These findings suggest that vitamin D deficiency during development has epigenetic consequences impacting the systemic metabolic milieu. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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