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.
Highlights
Obesity is marked by excessive body fat accumulation
As Pigment epithelium-derived factor (PEDF) is highly expressed in the adipocytes, in the current study, we investigated its biological functions associated with adipogenesis
Using rat adipose-derived stem cells (AdSCs) and a mouse pre-adipocyte cell line 3T3-L1, we found that the PEDF decrease during adipogenic differentiation was accompanied by a concomitant increase in the scavenger receptor CD36, which played a direct functional role in the adipogenic process
Summary
Obesity is marked by excessive body fat accumulation. the adipose tissue is the primary organ crucial for energy storage in mammals, excessive fat accumulation can cause severe health issues. Clinical studies have demonstrated elevated PEDF levels in obese population and patients with type 2 diabetes, which are positively correlated with insulin resistance [13,14]. These associations highlight PEDF as an important metabolic regulatory protein. Using rat adipose-derived stem cells (AdSCs) and a mouse pre-adipocyte cell line 3T3-L1, we found that the PEDF decrease during adipogenic differentiation was accompanied by a concomitant increase in the scavenger receptor CD36, which played a direct functional role in the adipogenic process. Our results explain from a molecular perspective that PEDF may have beneficial effects in inhibition of adipogenesis
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