title: The orphan nuclear receptor small heterodimer partner is required for thiazolidinedione effects in leptin-deficient mice.
abstract: BACKGROUND
  Small heterodimer partner (SHP, NR0B2) is involved in diverse metabolic pathways, including hepatic bile acid, lipid and glucose homeostasis, and has been implicated in effects on the peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and the receptor for antidiabetic drugs thiazolidinediones (TZDs). In this study, we aim to investigate the role of SHP in TZD response by comparing TZD-treated leptin-deficient (ob/ob) and leptin-, SHP-deficient (ob/ob;Shp(-/-)) double mutant mice.
  
  
  RESULTS
  Both ob/ob and double mutant ob/ob;Shp(-/-) mice developed hyperglycemia, insulin resistance, and hyperlipidemia, but hepatic fat accumulation was decreased in the double mutant ob/ob;Shp(-/-) mice. PPARγ2 mRNA levels were markedly lower in ob/ob;Shp(-/-) liver and decreased to a lesser extent in adipose tissue. The TZD troglitazone did not reduce glucose or circulating triglyceride levels in ob/ob;Shp(-/-) mice. Expression of the adipocytokines, such as adiponectin and resistin, was not stimulated by troglitazone treatment. Expression of hepatic lipogenic genes was also reduced in ob/ob;Shp(-/-) mice. Moreover, overexpression of SHP by adenovirus infection increased PPARγ2 mRNA levels in mouse primary hepatocytes.
  
  
  CONCLUSIONS
  Our results suggest that SHP is required for both antidiabetic and hypolipidemic effects of TZDs in ob/ob mice through regulation of PPARγ expression.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA. httseng@most.gov.tw.
authors.forename: Hsiu-Ting
authors.initials: HT
authors.lastname: Tseng
authors.affiliation: 300 Gumi-dong, Bundang-gu, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Kyeonggi-do, South Korea. yjparkmd@snu.ac.kr.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA. ylee3@neomed.edu.
authors.forename: Yoon Kwang
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA. moore@bcm.tmc.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Moore
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D020738:Leptin / Q000172:deficiency / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008820:Mice, Obese; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage*
chemical_list: D001647:Bile Acids and Salts; D007328:Insulin; D020738:Leptin; D047495:PPAR gamma; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; C099713:nuclear receptor subfamily 0, group B, member 2; C089946:2,4-thiazolidinedione; D005947:Glucose