GIPR Is Predominantly Localized to Nonadipocyte Cell Types Within White Adipose Tissue.
Authors
Campbell, Jonathan E
Beaudry, Jacqueline L
Svendsen, Berit
Baggio, Laurie L
Gordon, Andrew N
Wong, Chi Kin
Reimann, Frank
Publication Date
2022-05-01Journal Title
Diabetes
ISSN
0012-1797
Publisher
American Diabetes Association
Volume
71
Issue
5
Pages
1115-1127
Type
Article
This Version
AM
Physical Medium
Print
Metadata
Show full item recordCitation
Campbell, J. E., Beaudry, J. L., Svendsen, B., Baggio, L. L., Gordon, A. N., Ussher, J. R., Wong, C. K., et al. (2022). GIPR Is Predominantly Localized to Nonadipocyte Cell Types Within White Adipose Tissue.. Diabetes, 71 (5), 1115-1127. https://doi.org/10.2337/db21-1166
Abstract
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.
Keywords
Adipose Tissue, White, Animals, Gastric Inhibitory Polypeptide, Glucose, Mice, Receptors, Gastrointestinal Hormone
Sponsorship
MRC (MC_UU_00014/3)
Wellcome Trust (100574/Z/12/Z)
Wellcome Trust (106262/Z/14/Z)
Medical Research Council (MC_UU_12012/3)
Identifiers
External DOI: https://doi.org/10.2337/db21-1166
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336993
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