GIPR Is Predominantly Localized to Nonadipocyte Cell Types Within White Adipose Tissue.

Journal Article (Journal Article)

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) augments glucose-dependent insulin secretion through its receptor expressed on islet β-cells. GIP also acts on adipose tissue; yet paradoxically, both enhanced and reduced GIP receptor (GIPR) signaling reduce adipose tissue mass and attenuate weight gain in response to nutrient excess. Moreover, the precise cellular localization of GIPR expression within white adipose tissue (WAT) remains uncertain. We used mouse genetics to target Gipr expression within adipocytes. Surprisingly, targeting Cre expression to adipocytes using the adiponectin (Adipoq) promoter did not produce meaningful reduction of WAT Gipr expression in Adipoq-Cre:Giprflx/flx mice. In contrast, adenoviral expression of Cre under the control of the cytomegalovirus promoter, or transgenic expression of Cre using nonadipocyte-selective promoters (Ap2/Fabp4 and Ubc) markedly attenuated WAT Gipr expression. Analysis of single-nucleus RNA-sequencing, adipose tissue data sets localized Gipr/GIPR expression predominantly to pericytes and mesothelial cells rather than to adipocytes. Together, these observations reveal that adipocytes are not the major GIPR+ cell type within WAT-findings with mechanistic implications for understanding how GIP and GIP-based co-agonists control adipose tissue biology.

Full Text

Duke Authors

Cited Authors

  • Campbell, JE; Beaudry, JL; Svendsen, B; Baggio, LL; Gordon, AN; Ussher, JR; Wong, CK; Gribble, FM; D'Alessio, DA; Reimann, F; Drucker, DJ

Published Date

  • May 1, 2022

Published In

Volume / Issue

  • 71 / 5

Start / End Page

  • 1115 - 1127

PubMed ID

  • 35192688

Pubmed Central ID

  • PMC7612781

Electronic International Standard Serial Number (EISSN)

  • 1939-327X

Digital Object Identifier (DOI)

  • 10.2337/db21-1166

Language

  • eng

Conference Location

  • United States