Format

Send to

Choose Destination
Nat Commun. 2019 Jul 3;10(1):2936. doi: 10.1038/s41467-019-11003-4.

Adipocyte β-arrestin-2 is essential for maintaining whole body glucose and energy homeostasis.

Author information

1
Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, NIH-20892, USA.
2
Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA.
3
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA.
4
Center for Molecular Medicine, National Heart, Lung, and Blood Institute, Bethesda, MD, 20892, USA.
5
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA.
6
Department of Cell Biology, Duke University Medical Center, Durham, NC, 27710, USA.
7
Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, NIH-20892, USA. jurgenw@niddk.nih.gov.

Abstract

β-Arrestins are major regulators of G protein-coupled receptor-mediated signaling processes. Their potential roles in regulating adipocyte function in vivo remain unexplored. Here we report the novel finding that mice lacking β-arrestin-2 (barr2) selectively in adipocytes show significantly reduced adiposity and striking metabolic improvements when consuming excess calories. We demonstrate that these beneficial metabolic effects are due to enhanced signaling through adipocyte β3-adrenergic receptors (β3-ARs), indicating that barr2 represents a potent negative regulator of adipocyte β3-AR activity in vivo. Interestingly, essentially all beneficial metabolic effects caused by adipocyte barr2 deficiency are absent in adipocyte barr2-PRDM16 double KO mice, indicating that the metabolic improvements caused by the lack of barr2 in adipocytes are mediated by the browning/beiging of white adipose tissue. Our data support the novel concept that 'G protein-biased' β3-AR agonists that do not promote β3-AR/barr2 interactions may prove useful for the treatment of obesity and related metabolic disorders.

PMID:
31270323
PMCID:
PMC6610117
DOI:
10.1038/s41467-019-11003-4
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center