Regulation of Apo E Expression by the Nuclear Receptors- LXRs and FXR

Author(s): Anne Perez, Eric J. Niesor.

Journal Name: Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents

Volume 3 , Issue 3 , 2003

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Abstract:

The nuclear receptors, LXRs and FXR, are important regulators of lipid homeostasis. Among their identified target genes is Apo E, which is a well-established plasma lipid transport protein. This lipoprotein has been extensively studied and a wide range of excellent reviews is available on it. Here, we reviewed the current status of Apo E regulation by LXRs and FXR, although a handful of publications are available on this topic. Functional response elements for LXRs and FXR have been identified in the Apo E / C-I / C-IV / C-II gene cluster. The emerging picture is that FXR regulates Apo E expression in the liver, whereas LXRs play a similar role in extrahepatic tissues. We further investigated the regulation of Apo E expression through LXR and FXR activation in liver- (HepG2), monocyte- (THP-1) and colon- (Caco-2) derived cell lines. Apo E transcript levels are increased in these three cell lines in response to LXR activation by the specific agonist T0901317. Upon FXR stimulation by GW4064, Apo E mRNA levels are increased in HepG2 and Caco-2, but not in the THP-1 cells, which do not express FXR. Interestingly, in the liver-derived HepG2 and colon-derived Caco-2 cell lines, which both express LXRs and FXR, Apo E expression can be controlled either by LXRs or FXR. In summary, these nuclear receptors display both distinct and overlapping functions in lipid metabolism. Apo E can be regulated by either LXRs or FXR, thus providing alternative mechanisms that control lipid homeostasis in different tissues.

Keywords: apo e, lxrs, fxr

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2003
Page: [245 - 249]
Pages: 5
DOI: 10.2174/1568013033483348
Price: $58