title: C333H ameliorated insulin resistance through selectively modulating peroxisome proliferator-activated receptor γ in brown adipose tissue of db/db mice.
abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a unique target for insulin sensitizer agents. These drugs have been used for the clinical treatment of type 2 diabetes for almost twenty years. However, serious safety issues are associated with the PPARγ agonist thiazolidinediones (TZDs). Selective PPARγ modulators (SPPARMs) which retain insulin sensitization without TZDs-like side effects are emerging as a promising new generation of insulin sensitizers. C333H is a novel structure compound synthesized by our laboratory. In diabetic rodent models, C333H has insulin-sensitizing and glucose-lowering activity comparable to that of TZDs, and causes no significant increase in body weight or adipose tissue weight in db/db mice. In diabetic db/db mice, C333H elevated circulating high molecular weight adiponectin isoforms, decreased PPARγ 273 serine phosphorylation in brown adipose tissue and selectively modulated the expression of a subset of PPARγ target genes in adipose tissue. In vitro, C333H weakly recruited coactivator and weakly dissociated corepressor activity. These findings suggest that C333H has similar properties to SPPARMs and may be a potential therapeutic agent for the treatment of type 2 diabetes.
authors.affiliation: Institute of Radiation Medicine, Peking Union Medical College &Chinese Academy of Medical Sciences, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Xinbo
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhou
authors.forename: Xinni
authors.initials: X
authors.lastname: Xie
authors.forename: Aimin
authors.initials: A
authors.lastname: Meng
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D045744:Cell Line, Tumor; D003920:Diabetes Mellitus / Q000378:metabolism*; D005663:Furans / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D009765:Obesity / Q000097:blood / Q000139:chemically induced; D009929:Organ Size / Q000187:drug effects; D010080:Oxazoles / Q000494:pharmacology*; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012970:Sodium Glutamate
chemical_list: D001786:Blood Glucose; C513069:C333H compound; D005663:Furans; D007328:Insulin; D020738:Leptin; D010080:Oxazoles; D047495:PPAR gamma; D012970:Sodium Glutamate