期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 19, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms19123992
关键词
pigment epithelium-derived factor; adipogenic differentiation; adipose-derived stem cells; CD36; adipose triglyceride lipase
资金
- Ministry of Science and Technology of Taiwan [MOST 107-2320-B-182A-027, MOST 104-2314-B-182A-018, MOST 105-2314-B-182A-037-MY2]
- Chang Gung Medical Foundation [CMRPG8G1381, CMRPG8D1033, CMRPG8H0661, CMRPG8F0562, CMRPG8D1023, CMRPG8C0952, CMRPG8D1013]
Adipogenesis is a tightly regulated cellular process that involves the action of multiple signaling pathways. Characterization of regulators that are associated with adipose development is crucial to understanding the mechanisms underlying obesity and other metabolic disorders. Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein that was first described as a neurotrophic factor. The role of PEDF in lipid metabolism was established when adipose triglyceride lipase (ATGL), a major triglyceride hydrolase, was characterized as its binding partner. In this study, we investigated the downstream effects of PEDF on adipogenic differentiation using rat adipose-derived stem cells (AdSCs) and the mouse pre-adipocyte cell line 3T3-L1. Knocking down PEDF in differentiating cells resulted in elevated levels of ATGL and CD36, as well as other adipogenic markers, with a concomitant increase in adipocyte number. CD36, a scavenger receptor for a variety of ligands, regulated proliferation and lipogenic gene expression during adipogenesis. The CD36 increase due to PEDF down-regulation might be a result of elevated PPAR. We further demonstrated that PEDF expression was regulated by dexamethasone, a synthetic glucocorticoid that is widely used for adipogenesis at the transcriptional level. Taken together, our findings highlight that PEDF negatively regulates adipogenesis through the regulation of various signaling intermediates, and it may play a crucial role in lipid metabolic disorders.
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