TY - JOUR
T1 - Regulation of Lipoprotein Lipase by the Oxysterol Receptors, LXRα and LXRβ
AU - Zhang, Yuan
AU - Repa, Joyce J.
AU - Gauthier, Karine
AU - Mangelsdorf, David J.
PY - 2001/11/16
Y1 - 2001/11/16
N2 - Lipoprotein lipase (LPL) is a key enzyme for lipoprotein metabolism and is responsible for hydrolysis of triglycerides in circulating lipoproteins, releasing free fatty acids to peripheral tissues. In liver, LPL is also believed to promote uptake of high density lipoprotein (HDL)-cholesterol and thereby facilitate reverse cholesterol transport. In this study we show that the Lpl gene is a direct target of the oxysterol liver X receptor, LXRα. Mice fed diets containing high cholesterol or an LXR-selective agonist exhibited a significant increase in LPL expression in the liver and macrophages, but not in other tissues (e.g. adipose and muscle). Studies in Lxr-deficient mice confirmed that this response was dependent more on the presence of LXRα than LXRβ. Analysis of the Lpl gene revealed the presence of a functional DR4 LXR response element in the intronic region between exons 1 and 2. This response element directly binds rexinoid receptor (RXR)/LXR heterodimers and is sufficient for rexinoid- and LXR agonist-induced transcription of the Lpl gene. Together, these studies further distinguish the roles of LXRα and β and support a growing body of evidence that LXRs function as key regulators of lipid metabolism and are anti-atherogenic.
AB - Lipoprotein lipase (LPL) is a key enzyme for lipoprotein metabolism and is responsible for hydrolysis of triglycerides in circulating lipoproteins, releasing free fatty acids to peripheral tissues. In liver, LPL is also believed to promote uptake of high density lipoprotein (HDL)-cholesterol and thereby facilitate reverse cholesterol transport. In this study we show that the Lpl gene is a direct target of the oxysterol liver X receptor, LXRα. Mice fed diets containing high cholesterol or an LXR-selective agonist exhibited a significant increase in LPL expression in the liver and macrophages, but not in other tissues (e.g. adipose and muscle). Studies in Lxr-deficient mice confirmed that this response was dependent more on the presence of LXRα than LXRβ. Analysis of the Lpl gene revealed the presence of a functional DR4 LXR response element in the intronic region between exons 1 and 2. This response element directly binds rexinoid receptor (RXR)/LXR heterodimers and is sufficient for rexinoid- and LXR agonist-induced transcription of the Lpl gene. Together, these studies further distinguish the roles of LXRα and β and support a growing body of evidence that LXRs function as key regulators of lipid metabolism and are anti-atherogenic.
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U2 - 10.1074/jbc.M107823200
DO - 10.1074/jbc.M107823200
M3 - Article
C2 - 11562371
AN - SCOPUS:0035900749
SN - 0021-9258
VL - 276
SP - 43018
EP - 43024
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -