American Diabetes Association

TABLE 1

LXR target genes

	Function	Direction	Reference
Lipid cholesterol metabolism
Cyp7α^*	Rate-limiting enzyme in the conversion of cholesterol to bile acids	↑ LXRE	43
CETP	Mediates transfer of cholesterol esters from HDL to triglyceride-rich lipoproteins	↑ LXRE	44
ABCA1	Mediates the active efflux of cholesterol from cells to apolipoproteins	↑ LXRE	6,7,45,46
ABCG1	Mediates the active efflux of cholesterol and phospholipids from cells to apolipoproteins	↑	8
ABCG4	Cellular transmembrane transport of endogenous lipid substrates	↑	9
ABCG5/8	Important role in entero-hepatic sterol transport	↑	47
SREBP1c	Transcription factor that regulates expression of lipogenic enzymes	↑ LXRE	13,14,48
SCD-1/2	Rate-limiting enzyme in the cellular synthesis of monounsaturated fatty acids from saturated fatty acids, an important step in producing triglycerides	↑	20 ^§
FAS	Catalyzes the formation of long-chain fatty acids from acetyl-CoA	↑ LXRE	16,20
ACC	Carboxylation of acetyl-CoA to malonyl-CoA for the synthesis of long-chain fatty acids	↑ T3RE^†	17,20
ApoE	Facilitates cholesterol efflux outside the enterohepatic axis	↑ LXRE	11,12
ApoC	Cofactor for LPL in hydrolysis of triglyceride	↑ LXRE	12
LXRα	Autoregulation	↑ LXRE	49,50
LPL	Hydrolyzes triglycerides in circulating large lipoproteins	↑ LXRE	51
PLTP	Transfer phospholipids from triglyceride-rich lipoproteins to HDL	↑	52
SR-B1	HDL receptor involved in reverse cholesterol transport	↑ LXRE	53
Angpt13	A family member of the secreted growth factor angiopoietins	↑ LXRE	21
Carbohydrate metabolism
PEPCK	Rate-limiting enzyme in gluconeogenesis	↓	24–26
Fbp1	Gluconeogenic enzyme	↓	24
G6P	Glucose-6-phosphatase	↓	24,26
Pfkfb3	Glycolytic enzyme	↓	24
PDK4	Glycolysis inhibitor	↑	24
GLUT4	Glucose transporter	↑	24
Inflammatory response
TNF-α	Proinflammatory cytokine	↑/↓ LXRE	36,54
iNOS	Inflammatory mediator	↓	37
Cox-2	Inflammatory mediator	↓	37
IL-6	Inflammatory mediator	↓	37
Energy homeostasis
UCP-1	Proton carrier in the mitochondrial membrane	↓	24 ^§
Others
Renin	Generates angiotensin from angiotensinogen, initiating a cascade of reactions that produces an elevation of blood pressure and increased sodium retention by the kidney	↑ CNRE^‡	39
c-myc	Transcription factor that seems to activate the transcription of growth-related genes	↑ CNRE^‡	39
11β-HSD-1	Catalyzes the conversion of inactive cortisone to active cortisol	↓	25

	Function	Direction	Reference
Lipid cholesterol metabolism
Cyp7α^*	Rate-limiting enzyme in the conversion of cholesterol to bile acids	↑ LXRE	43
CETP	Mediates transfer of cholesterol esters from HDL to triglyceride-rich lipoproteins	↑ LXRE	44
ABCA1	Mediates the active efflux of cholesterol from cells to apolipoproteins	↑ LXRE	6,7,45,46
ABCG1	Mediates the active efflux of cholesterol and phospholipids from cells to apolipoproteins	↑	8
ABCG4	Cellular transmembrane transport of endogenous lipid substrates	↑	9
ABCG5/8	Important role in entero-hepatic sterol transport	↑	47
SREBP1c	Transcription factor that regulates expression of lipogenic enzymes	↑ LXRE	13,14,48
SCD-1/2	Rate-limiting enzyme in the cellular synthesis of monounsaturated fatty acids from saturated fatty acids, an important step in producing triglycerides	↑	20 ^§
FAS	Catalyzes the formation of long-chain fatty acids from acetyl-CoA	↑ LXRE	16,20
ACC	Carboxylation of acetyl-CoA to malonyl-CoA for the synthesis of long-chain fatty acids	↑ T3RE^†	17,20
ApoE	Facilitates cholesterol efflux outside the enterohepatic axis	↑ LXRE	11,12
ApoC	Cofactor for LPL in hydrolysis of triglyceride	↑ LXRE	12
LXRα	Autoregulation	↑ LXRE	49,50
LPL	Hydrolyzes triglycerides in circulating large lipoproteins	↑ LXRE	51
PLTP	Transfer phospholipids from triglyceride-rich lipoproteins to HDL	↑	52
SR-B1	HDL receptor involved in reverse cholesterol transport	↑ LXRE	53
Angpt13	A family member of the secreted growth factor angiopoietins	↑ LXRE	21
Carbohydrate metabolism
PEPCK	Rate-limiting enzyme in gluconeogenesis	↓	24–26
Fbp1	Gluconeogenic enzyme	↓	24
G6P	Glucose-6-phosphatase	↓	24,26
Pfkfb3	Glycolytic enzyme	↓	24
PDK4	Glycolysis inhibitor	↑	24
GLUT4	Glucose transporter	↑	24
Inflammatory response
TNF-α	Proinflammatory cytokine	↑/↓ LXRE	36,54
iNOS	Inflammatory mediator	↓	37
Cox-2	Inflammatory mediator	↓	37
IL-6	Inflammatory mediator	↓	37
Energy homeostasis
UCP-1	Proton carrier in the mitochondrial membrane	↓	24 ^§
Others
Renin	Generates angiotensin from angiotensinogen, initiating a cascade of reactions that produces an elevation of blood pressure and increased sodium retention by the kidney	↑ CNRE^‡	39
c-myc	Transcription factor that seems to activate the transcription of growth-related genes	↑ CNRE^‡	39
11β-HSD-1	Catalyzes the conversion of inactive cortisone to active cortisol	↓	25

Only genes with an LXR response element found in the promoter or regulated by exposure to an LXR agonist are included. ↑, Upregulated; ↓, downregulated.

Not directly LXR regulated in humans (42).

†

LXR is involved in a complex that binds a thyroid hormone (triiodothyronine, T3) response element.

‡

Response to LXR mediated through a cis-acting DNA element (CNRE).

K.R.S., S.Y. Neo, T.M. Stulnig, V.B. Vega, S.S. Rahman, G. Schuster, J.-Å.G., and E.T. Liu, unpublished data.

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