PMID- 9484993
OWN - NLM
STAT- MEDLINE
DCOM- 19980319
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 18
IP  - 2
DP  - 1998 Feb
TI  - RXR agonists activate PPARalpha-inducible genes, lower triglycerides, and raise 
      HDL levels in vivo.
PG  - 272-6
AB  - Peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors 
      (RXRs) are members of the intracellular receptor superfamily. PPARs bind to 
      peroxisome proliferator-response elements (PPREs) as heterodimers with RXR and as 
      such activate gene transcription in response to activators. Fibrates like 
      gemfibrozil are well-known PPARalpha activators and are used in the treatment of 
      hyperlipidemia. We show that the RXR ligand LGD1069 (Targretin), like 
      gemfibrozil, can activate the PPARalpha/RXR signal-transduction pathway, 
      including transactivation of the bifunctional enzyme or acyl-CoA oxidase response 
      elements in a cotransfection assay. The activation also occurs in vivo, whereby 
      in rats treated with LGD1069 or gemfibrozil, bifunctional enzyme and acyl-CoA 
      oxidase RNA are induced and the combination of LGD1069 and gemfibrozil leads to a 
      greater induction. Importantly, in hypertriglyceridemic db/db mice treated with 
      RXR or PPARalpha agonists, triglyceride levels are lowered, and the combination 
      again has significantly greater efficacy. RXR agonists also raise HDL cholesterol 
      levels without changing apoA-I RNA expression. This observation suggests the use 
      of RXR-selective agonists, "rexinoids," either alone or in combination with a 
      fibrate as a new therapeutic approach to treating patients with high triglyceride 
      and low HDL cholesterol levels.
FAU - Mukherjee, R
AU  - Mukherjee R
AD  - Department of Pharmacology, Ligand Pharmaceuticals, Inc, San Diego, Calif. 92121, 
      USA. mukherjee@ligand.com
FAU - Strasser, J
AU  - Strasser J
FAU - Jow, L
AU  - Jow L
FAU - Hoener, P
AU  - Hoener P
FAU - Paterniti, J R Jr
AU  - Paterniti JR Jr
FAU - Heyman, R A
AU  - Heyman RA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Drug Combinations)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Transcription Factors)
RN  - 0 (Triglycerides)
RN  - A61RXM4375 (Bexarotene)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.3.3.6 (Acyl-CoA Oxidase)
RN  - Q8X02027X3 (Gemfibrozil)
SB  - IM
MH  - Acyl-CoA Oxidase
MH  - Animals
MH  - Bexarotene
MH  - Cholesterol, HDL/*blood
MH  - Drug Combinations
MH  - Female
MH  - Gemfibrozil/pharmacology
MH  - Gene Expression Regulation/*physiology
MH  - Hypertriglyceridemia/blood/genetics
MH  - Hypolipidemic Agents/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Oxidoreductases/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cytoplasmic and Nuclear/*physiology
MH  - Receptors, Retinoic Acid/*agonists
MH  - Retinoid X Receptors
MH  - Signal Transduction/drug effects
MH  - Tetrahydronaphthalenes/pharmacology
MH  - Transcription Factors/*agonists/*physiology
MH  - Transcriptional Activation/genetics
MH  - Triglycerides/*blood
EDAT- 1998/03/04 03:05
MHDA- 2001/03/28 10:01
CRDT- 1998/03/04 03:05
PHST- 1998/03/04 03:05 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1998/03/04 03:05 [entrez]
AID - 10.1161/01.atv.18.2.272 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1998 Feb;18(2):272-6. doi: 
      10.1161/01.atv.18.2.272.