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

Adams, M, Montague, CT, Prins, JB, Holder, JC, Smith, SA, Sanders, L, Digby, JE, Sewter, CP, Lazar, MA, Chatterjee, VKK and O'Rahilly, S (1997) Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation. Journal of Clinical Investigation, 100 12: 3149-3153. doi:10.1172/JCI119870


Author Adams, M
Montague, CT
Prins, JB
Holder, JC
Smith, SA
Sanders, L
Digby, JE
Sewter, CP
Lazar, MA
Chatterjee, VKK
O'Rahilly, S
Title Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
Publication date 1997-12-01
Year available 1997
Sub-type Article (original research)
DOI 10.1172/JCI119870
Open Access Status DOI
Volume 100
Issue 12
Start page 3149
End page 3153
Total pages 5
Place of publication NEW YORK
Publisher ROCKEFELLER UNIV PRESS
Language eng
Abstract 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 PPAR gamma 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-deoxy Delta(12,14)prostaglandin J(2) (a natural PPAR gamma 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 PPAR gamma. In contrast, preadipocytes from Om sites in the same individuals were refractory to TZDs, although PPAR gamma 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.
Keyword thiazolidinediones
human adipocyte differentiation
peroxisome proliferator-activated receptor
insulin resistance
Gene-Expression
Ppar-Gamma
Adipocyte Differentiation
Transcription Factor
Db/db Mice
Acid
Phosphorylation
Fibroblasts
Metabolism
Rodents
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID DK-49780
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: ResearcherID Downloads - Archived
 
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