TAZ Is a Negative Regulator of PPARγ Activity in Adipocytes and TAZ Deletion Improves Insulin Sensitivity and Glucose Tolerance

Cell Metab. 2020 Jan 7;31(1):162-173.e5. doi: 10.1016/j.cmet.2019.10.003. Epub 2019 Nov 7.


Insulin resistance is a major factor in obesity-linked type 2 diabetes. PPARγ is a master regulator of adipogenesis, and small molecule agonists, termed thiazolidinediones, are potent therapeutic insulin sensitizers. Here, we studied the role of transcriptional co-activator with PDZ-binding motif (TAZ) as a transcriptional co-repressor of PPARγ. We found that adipocyte-specific TAZ knockout (TAZ AKO) mice demonstrate a constitutively active PPARγ state. Obese TAZ AKO mice show improved glucose tolerance and insulin sensitivity compared to littermate controls. PPARγ response genes are upregulated in adipose tissue from TAZ AKO mice and adipose tissue inflammation was also decreased. In vitro and in vivo mechanistic studies revealed that the TAZ-PPARγ interaction is partially dependent on ERK-mediated Ser112 PPARγ phosphorylation. As adipocyte PPARγ Ser112 phosphorylation is increased in obesity, repression of PPARγ activity by TAZ could contribute to insulin resistance. These results identify TAZ as a new factor in the development of obesity-induced insulin resistance.

Keywords: Hippo pathway; PPAR gamma; TAZ; adipocyte; glucose tolerance; insulin sensitivity; obesity; transcriptional co-activator with PDZ-binding motif.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adipocytes / enzymology
  • Adipocytes / metabolism*
  • Adipogenesis / genetics
  • Animals
  • Cell Line
  • Diet, High-Fat
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Humans
  • Immunohistochemistry
  • Inflammation / genetics
  • Inflammation / metabolism
  • Insulin Resistance / genetics*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Phosphorylation
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Adaptor Proteins, Signal Transducing
  • PPAR gamma
  • Trans-Activators
  • Wwtr1 protein, mouse
  • Extracellular Signal-Regulated MAP Kinases
  • Glucose