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Visualization and Quantification of Mesenchymal Cell Adipogenic Differentiation Potential with a Lineage Specific Marker
Published on: March 31, 2018
Decreased PEDF Expression Promotes Adipogenic Differentiation through the Up-Regulation of CD36
Kuang-Tzu Huang1,2, Li-Wen Hsu3, Kuang-Den Chen4,5
1Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan. huangkt@cgmh.org.tw.
Insights
Pigment epithelium-derived factor (PEDF) negatively regulates fat cell formation (adipogenesis). Lowering PEDF increases adipocyte differentiation and lipid metabolism markers, suggesting PEDF
Area of Science:
- Cell Biology
- Metabolic Disorders
- Molecular Endocrinology
Background:
- Adipogenesis is a complex, regulated process vital for understanding obesity and metabolic diseases.
- Pigment epithelium-derived factor (PEDF), a glycoprotein, is known for neurotrophic roles and its partnership with adipose triglyceride lipase (ATGL).
Purpose of the Study:
- To investigate the impact of PEDF on adipogenic differentiation.
- To elucidate the role of PEDF in regulating key adipogenesis and lipid metabolism markers.
Main Methods:
- Utilized rat adipose-derived stem cells (AdSCs) and mouse 3T3-L1 pre-adipocytes.
- Employed gene knockdown techniques to reduce PEDF levels during differentiation.
- Quantified adipogenic and lipogenic markers, including ATGL and CD36, and analyzed PPARγ regulation.
Main Results:
- PEDF knockdown led to increased levels of ATGL, CD36, and other adipogenic markers, enhancing adipocyte differentiation.
- CD36 was identified as a regulator of proliferation and lipogenic gene expression, with its increase linked to elevated PPARγ following PEDF down-regulation.
- Dexamethasone was found to regulate PEDF expression transcriptionally, a common inducer of adipogenesis.
Conclusions:
- PEDF acts as a negative regulator of adipogenesis by modulating signaling intermediates like ATGL and CD36.
- The findings suggest PEDF's critical involvement in lipid metabolism and its potential role in metabolic disorders.
- PEDF's expression is influenced by dexamethasone, highlighting a link between glucocorticoids and adipogenesis regulation.
Abstract:
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 PPARγ. 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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