Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation

J Clin Invest. 1997 Dec 15;100(12):3149-53. doi: 10.1172/JCI119870.


Activation of peroxisome proliferator-activated receptor (PPAR) gamma, a nuclear receptor highly expressed in adipocytes, induces the differentiation of murine preadipocyte cell lines. Recently, thiazolidinediones (TZDs), a novel class of insulin-sensitizing compounds effective in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) have been shown to bind to PPARgamma with high affinity. We have examined the effects of these compounds on the differentiation of human preadipocytes derived from subcutaneous (SC) and omental (Om) fat. Assessed by lipid accumulation, glycerol 3-phosphate dehydrogenase activity, and mRNA levels, subcultured preadipocytes isolated from either SC or Om depots did not differentiate in defined serum-free medium. Addition of TZDs (BRL49653 or troglitazone) or 15-deoxyDelta12,14prostaglandin J2 (a natural PPARgamma ligand) enhanced markedly the differentiation of preadipocytes from SC sites, assessed by all three criteria. The rank order of potency of these agents in inducing differentiation matched their ability to activate transcription via human PPARgamma. In contrast, preadipocytes from Om sites in the same individuals were refractory to TZDs, although PPARgamma was expressed at similar levels in both depots. The mechanism of this depot-specific TZD response is unknown. However, given the association between Om adiposity and NIDDM, the site-specific responsiveness of human preadipocytes to TZDs may be involved in the beneficial effects of these compounds on in vivo insulin sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Chromans / pharmacology*
  • Humans
  • Mice
  • Microbodies
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology
  • Receptors, Cytoplasmic and Nuclear / biosynthesis
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Rosiglitazone
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcriptional Activation / drug effects
  • Troglitazone


  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Chromans
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Rosiglitazone
  • Troglitazone
  • Prostaglandin D2