RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro
Fat distribution is an independent cardiometabolic risk factor. However, its molecular and cellular underpinnings remain obscure. Here we demonstrate that two independent GWAS signals at RSPO3, which are associated with increased body mass index-adjusted waist-to-hip ratio, act to specifically incre...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2020
|
| _version_ | 1797074225733828608 |
|---|---|
| author | Loh, NY Minchin, JE Loh, NY Pinnick, KE Verma, M Verma, M Denton, N Neville, M McCarthy, M Mahajan, A Karpe, F Christodoulides, C |
| author_facet | Loh, NY Minchin, JE Loh, NY Pinnick, KE Verma, M Verma, M Denton, N Neville, M McCarthy, M Mahajan, A Karpe, F Christodoulides, C |
| author_sort | Loh, NY |
| collection | OXFORD |
| description | Fat distribution is an independent cardiometabolic risk factor. However, its molecular and cellular underpinnings remain obscure. Here we demonstrate that two independent GWAS signals at RSPO3, which are associated with increased body mass index-adjusted waist-to-hip ratio, act to specifically increase RSPO3 expression in subcutaneous adipocytes. These variants are also associated with reduced lower-body fat, enlarged gluteal adipocytes and insulin resistance. Based on human cellular studies RSPO3 may limit gluteofemoral adipose tissue (AT) expansion by suppressing adipogenesis and increasing gluteal adipocyte susceptibility to apoptosis. RSPO3 may also promote upper-body fat distribution by stimulating abdominal adipose progenitor (AP) proliferation. The distinct biological responses elicited by RSPO3 in abdominal versus gluteal APs in vitro are associated with differential changes in WNT signalling. Zebrafish carrying a nonsense rspo3 mutation display altered fat distribution. Our study identifies RSPO3 as an important determinant of peripheral AT storage capacity. |
| first_indexed | 2024-03-06T23:33:04Z |
| format | Journal article |
| id | oxford-uuid:6cb86e0f-cc0e-4bf5-86d7-da85300193e1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:33:04Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:6cb86e0f-cc0e-4bf5-86d7-da85300193e12022-03-26T19:12:59ZRSPO3 impacts body fat distribution and regulates adipose cell biology in vitroJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6cb86e0f-cc0e-4bf5-86d7-da85300193e1EnglishSymplectic ElementsSpringer Nature2020Loh, NYMinchin, JELoh, NYPinnick, KEVerma, MVerma, MDenton, NNeville, MMcCarthy, M Mahajan, AKarpe, FChristodoulides, CFat distribution is an independent cardiometabolic risk factor. However, its molecular and cellular underpinnings remain obscure. Here we demonstrate that two independent GWAS signals at RSPO3, which are associated with increased body mass index-adjusted waist-to-hip ratio, act to specifically increase RSPO3 expression in subcutaneous adipocytes. These variants are also associated with reduced lower-body fat, enlarged gluteal adipocytes and insulin resistance. Based on human cellular studies RSPO3 may limit gluteofemoral adipose tissue (AT) expansion by suppressing adipogenesis and increasing gluteal adipocyte susceptibility to apoptosis. RSPO3 may also promote upper-body fat distribution by stimulating abdominal adipose progenitor (AP) proliferation. The distinct biological responses elicited by RSPO3 in abdominal versus gluteal APs in vitro are associated with differential changes in WNT signalling. Zebrafish carrying a nonsense rspo3 mutation display altered fat distribution. Our study identifies RSPO3 as an important determinant of peripheral AT storage capacity. |
| spellingShingle | Loh, NY Minchin, JE Loh, NY Pinnick, KE Verma, M Verma, M Denton, N Neville, M McCarthy, M Mahajan, A Karpe, F Christodoulides, C RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro |
| title | RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro |
| title_full | RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro |
| title_fullStr | RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro |
| title_full_unstemmed | RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro |
| title_short | RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro |
| title_sort | rspo3 impacts body fat distribution and regulates adipose cell biology in vitro |
| work_keys_str_mv | AT lohny rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT minchinje rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT lohny rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT pinnickke rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT vermam rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT vermam rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT dentonn rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT nevillem rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT mccarthym rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT mahajana rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT karpef rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro AT christodoulidesc rspo3impactsbodyfatdistributionandregulatesadiposecellbiologyinvitro |