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The GIPR is Predominantly Localized to Non-Adipocyte Cell Types Within White Adipose Tissue

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posted on 22.02.2022, 20:45 by Jonathan E. Campbell, Jacqueline L. Beaudry, Berit Svendsen, Laurie L. Baggio, Andrew N. Gordon, John R. Ussher, Chi Kin Wong, Fiona M. Gribble, David A. D’Alessio, Frank Reimann, Daniel J. Drucker
The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) augments glucose-dependent insulin secretion through its receptor expressed on islet b-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. Here, 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 CMV promoter, or transgenic expression of Cre using non-adipocyte-selective promoters (Ap2/Fabp4 and Ubc) markedly attenuated WAT Gipr expression. Analysis of single nucleus RNA-seq 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.

Funding

Government of Canada > Canadian Institutes of Health Research > Institute of Nutrition, Metabolism and Diabetes 154321

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