Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway

Expansion of visceral white adipose tissue (vWAT) occurs in response to nutrient excess, and is a risk factor for metabolic disease. SPRY1, a feedback inhibitor of receptor tyrosine kinase (RTK) signaling, is expressed in PDGFRa+ adipocyte progenitor cells (APC) in vivo. Global deficiency of Spry1 i...

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Autores principales: Xuehui Yang, Shivangi Pande, Robert A. Koza, Robert Friesel
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Publicado: Taylor & Francis Group 2021
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Acceso en línea:https://doaj.org/article/dfd1f8d43a5c4d89876a7a582db6fd13
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spelling oai:doaj.org-article:dfd1f8d43a5c4d89876a7a582db6fd132021-11-04T15:00:45ZSprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway2162-39452162-397X10.1080/21623945.2021.1987634https://doaj.org/article/dfd1f8d43a5c4d89876a7a582db6fd132021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/21623945.2021.1987634https://doaj.org/toc/2162-3945https://doaj.org/toc/2162-397XExpansion of visceral white adipose tissue (vWAT) occurs in response to nutrient excess, and is a risk factor for metabolic disease. SPRY1, a feedback inhibitor of receptor tyrosine kinase (RTK) signaling, is expressed in PDGFRa+ adipocyte progenitor cells (APC) in vivo. Global deficiency of Spry1 in mice results in disproportionate postnatal growth of gonadal WAT (gWAT), while iWAT and BAT were similar in size between Spry1KO and WT mice. Spry1 deficiency increased the number of PDGFRa+ stromal vascular fraction (SVF) cells in gWAT and showed increased proliferation and fibrosis. Spry1KO gWAT had increased collagen deposition and elevated expression of markers of inflammation. In vitro, SPRY1 was transiently down regulated during early adipocyte differentiation of SVF cells, with levels increasing at later stages of differentiation. SPRY1 deficiency enhances PDGF-AA and PDGF-BB induced proliferation of SVF cells. Increased proliferation of SVF from Spry1KO gWAT accompanies an increase in AKT activation. PDGF-AA stimulated a transient down regulation of SPRY1 in wild type SVF, whereas PDGF-BB stimulated a sustained down regulation of SPRY1 in wild type SVF. Collectively, our data suggest that SPRY1 is critical for regulating postnatal growth of gWAT by restraining APC proliferation and differentiation in part by regulation of PDGFRa/b-AKT signaling.Xuehui YangShivangi PandeRobert A. KozaRobert FrieselTaylor & Francis Grouparticleadipocytesprouty1proliferationdifferentiationfibrosiscell signallingDiseases of the endocrine glands. Clinical endocrinologyRC648-665CytologyQH573-671PhysiologyQP1-981ENAdipocyte, Vol 10, Iss 1, Pp 574-586 (2021)
institution DOAJ
collection DOAJ
language EN
topic adipocyte
sprouty1
proliferation
differentiation
fibrosis
cell signalling
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
Cytology
QH573-671
Physiology
QP1-981
spellingShingle adipocyte
sprouty1
proliferation
differentiation
fibrosis
cell signalling
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
Cytology
QH573-671
Physiology
QP1-981
Xuehui Yang
Shivangi Pande
Robert A. Koza
Robert Friesel
Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway
description Expansion of visceral white adipose tissue (vWAT) occurs in response to nutrient excess, and is a risk factor for metabolic disease. SPRY1, a feedback inhibitor of receptor tyrosine kinase (RTK) signaling, is expressed in PDGFRa+ adipocyte progenitor cells (APC) in vivo. Global deficiency of Spry1 in mice results in disproportionate postnatal growth of gonadal WAT (gWAT), while iWAT and BAT were similar in size between Spry1KO and WT mice. Spry1 deficiency increased the number of PDGFRa+ stromal vascular fraction (SVF) cells in gWAT and showed increased proliferation and fibrosis. Spry1KO gWAT had increased collagen deposition and elevated expression of markers of inflammation. In vitro, SPRY1 was transiently down regulated during early adipocyte differentiation of SVF cells, with levels increasing at later stages of differentiation. SPRY1 deficiency enhances PDGF-AA and PDGF-BB induced proliferation of SVF cells. Increased proliferation of SVF from Spry1KO gWAT accompanies an increase in AKT activation. PDGF-AA stimulated a transient down regulation of SPRY1 in wild type SVF, whereas PDGF-BB stimulated a sustained down regulation of SPRY1 in wild type SVF. Collectively, our data suggest that SPRY1 is critical for regulating postnatal growth of gWAT by restraining APC proliferation and differentiation in part by regulation of PDGFRa/b-AKT signaling.
format article
author Xuehui Yang
Shivangi Pande
Robert A. Koza
Robert Friesel
author_facet Xuehui Yang
Shivangi Pande
Robert A. Koza
Robert Friesel
author_sort Xuehui Yang
title Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway
title_short Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway
title_full Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway
title_fullStr Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway
title_full_unstemmed Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway
title_sort sprouty1 regulates gonadal white adipose tissue growth through a pdgfrα/β-akt pathway
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/dfd1f8d43a5c4d89876a7a582db6fd13
work_keys_str_mv AT xuehuiyang sprouty1regulatesgonadalwhiteadiposetissuegrowththroughapdgfrabaktpathway
AT shivangipande sprouty1regulatesgonadalwhiteadiposetissuegrowththroughapdgfrabaktpathway
AT robertakoza sprouty1regulatesgonadalwhiteadiposetissuegrowththroughapdgfrabaktpathway
AT robertfriesel sprouty1regulatesgonadalwhiteadiposetissuegrowththroughapdgfrabaktpathway
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