TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression

Area of Science:

• Metabolic regulation
• Molecular biology
• Cell signaling

Background:

• Insulin signaling is crucial for blood glucose homeostasis.
• Dysregulation of insulin signaling contributes to metabolic syndrome.
• The precise regulatory mechanisms of insulin signaling remain incompletely understood.

Purpose of the Study:

• To identify novel regulators of insulin signaling.
• To elucidate the role of TAZ in insulin sensitivity.
• To investigate the interplay between TAZ, Hippo/Wnt pathways, and insulin action.

Main Methods:

• Muscle-specific TAZ-knockout mouse models.
• Analysis of insulin receptor substrate 1 (IRS1) expression.
• Assessment of Akt- and Glut4-mediated glucose uptake.
• Co-immunoprecipitation to study protein interactions.
• Investigation of Wnt signaling pathways.
• Statin administration studies in myoblasts.

Main Results:

• TAZ upregulates IRS1, enhancing Akt- and Glut4-mediated glucose uptake in muscle cells.
• Muscle-specific TAZ deficiency impairs insulin sensitivity and IRS1 expression.
• TAZ is essential for Wnt signaling-induced IRS1 expression.
• TAZ interacts with c-Jun and Tead4 to drive IRS1 transcription.
• Statins reduce TAZ, IRS1 levels, and insulin sensitivity, an effect reversed by constitutively active TAZ.

Conclusions:

• TAZ is a novel activator of insulin signaling, enhancing insulin sensitivity.
• TAZ bridges the Hippo and Wnt signaling pathways with insulin sensitivity.
• Targeting TAZ may offer therapeutic strategies for metabolic disorders.