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NIH Research Festival

September 14 – 16, 2016

Critical role of β-arrestin-2 in regulating adipocyte function and whole body glucose and energy homeostasis

Thursday, September 15, 2016 – Poster Session III
3:30 – 5:00 p.m.

FAES Terrace

NIDDK

MOLBIO-23

Authors

  • SP Pydi
  • S Jain
  • J Liu
  • T Finkel
  • J Wess

Abstract

In obese individuals, excess fat accumulates in adipose tissue, leading to altered adipose tissue metabolism and increased insulin resistance, a key feature of type 2 diabetes (T2D). Therefore, it is of great importance to understand the signaling pathways that regulate adipose tissue function. Activation of certain G protein coupled receptors (GPCRs) in adipose tissue has been reported to have beneficial effects on whole body glucose homeostasis. GPCR signaling is modulated by proteins of the β-arrestin family (barr1 and barr2), which can terminate GPCR signaling and/or mediate GPCR-independent signaling. Since recent studies have revealed that barr1 and barr2 regulate many important physiological functions, the in vivo roles of β-arrestins have become the focus of intense research. The potential importance of barr1 and barr2 in regulating adipocyte function and whole body glucose homeostasis remains unexplored. To shed light on this issue, we generated mutant mice that lack barr1 or barr2 (or both barr1 and barr2) selectively in adipocytes. Interestingly, adipo-barr2 KO mice maintained on a high-fat diet showed reduced body weight, improved glucose tolerance and enhanced insulin sensitivity. These mutant mice also displayed reduced subcutaneous adiposity and increased expression of thermogenic and beige fat markers. Our data support the novel concept that barr2 deficiency promotes beiging of WAT and improves whole body glucose metabolism, most likely by promoting signaling through adipocyte β-adrenergic receptors. These findings suggest that pharmacological inhibition of barr2 signaling in adipose tissue may prove clinically useful for the treatment of T2D.

Scientific Focus Area: Molecular Biology and Biochemistry

This page was last updated on Friday, March 26, 2021

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Download the 2016 Research Festival Schedule Overview (6 pages)

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