Targeting orphan nuclear receptor SHP in the treatment of metabolic diseases.
BACKGROUND
The orphan nuclear receptor small heterodimer partner (SHP; NR0B2) is an atypical nuclear receptor that contains a ligand-binding domain, but lacks the conserved DNA-binding domain. Since its discovery, SHP has been identified as a key transcriptional regulatory factor of genes involved in diverse metabolic pathways.


METHODS
We performed a Medline/Pubmed search to find published studies on the role of SHP in the regulation of metabolism in the liver, pancreatic islets, blood vessel, and kidney and on the feasibility of using SHP as a therapeutic target in metabolic disease.


RESULTS
In this review, we discuss the function of SHP as regulator of cholesterol, lipid and glucose metabolism, and the role of SHP in metabolic and fibrotic diseases.


CONCLUSIONS
The reviewed studies suggested that SHP could be a major target for therapeutic intervention in metabolic and fibrotic diseases, including metabolic syndrome and its complications. However, for SHP-targeted therapy, there are some outstanding issues, including the small number of known inducers of SHP and the lack of sufficient data in humans.
Keimyung University School of Medicine, Department of Internal Medicine, Daegu, 700-712, South Korea. kgpark@dsmc.or.kr
Mi-Kyung
MK
Kim
Dipanjan
D
Chanda
In-Kyu
IK
Lee
Hueng-Sik
HS
Choi
Keun-Gyu
KG
Park
D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D007674:Kidney Diseases / Q000503:physiopathology; D007680:Kidney Neoplasms / Q000503:physiopathology; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000503:physiopathology; D008659:Metabolic Diseases / Q000188:drug therapy*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects*
D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D002784:Cholesterol; D005947:Glucose