Peroxisome proliferator-activated receptor γ and its role in adipocyte homeostasis and thiazolidinedione-mediated insulin sensitization

Qiong A. Wang, Fang Zhang, Lei Jiang, Risheng Ye, Yu An, Mengle Shao, Caroline Tao, Rana K Gupta, Philipp E Scherer

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, peroxisome proliferator-activated receptor γ (PPARγ) is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPARγ in mature adipocytes in vivo. Short-term PPARγ deficiency in adipocytes reduces whole-body insulin sensitivity, but adipocytes are viable both in vitro and in vivo. However, after exposure to a high-fat diet, even short-term PPARγ deficiency leads to rapid adipocyte death. When mature adipocytes are depleted of both PPARγ and CCAAT-enhancer-binding protein α (C/EBPα), they are rapidly depleted of lipids and undergo adipocyte death, both in vitro and in vivo. Surprisingly, although thiazolidinediones (TZDs; PPARγ agonists) are thought to act mainly on PPARγ, PPARγ in adipocytes is not required for the whole-body insulinsensitizing effect of TZDs. This offers new mechanistic aspects of PPARγ/TZD action and its effect on whole-body metabolic homeostasis.

Original languageEnglish (US)
Article numbere00677
JournalMolecular and cellular biology
Volume38
Issue number10
DOIs
StatePublished - May 1 2018

Keywords

  • Adipocyte
  • Adipose tissue
  • C/EBPα
  • Inducible knockout
  • Insulin sensitization
  • Mouse model
  • Obesity
  • PPARγ
  • Thiazolidinedione

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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