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RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro.

Publication ,  Journal Article
Loh, NY; Minchin, JEN; Pinnick, KE; Verma, M; Todorčević, M; Denton, N; Moustafa, JE-S; Kemp, JP; Gregson, CL; Evans, DM; Neville, MJ ...
Published in: Nat Commun
June 3, 2020

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 3, 2020

Volume

11

Issue

1

Start / End Page

2797

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Wnt Signaling Pathway
  • Waist-Hip Ratio
  • Thrombospondins
  • Stem Cells
  • Sex Characteristics
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Mutation
 

Citation

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Chicago
ICMJE
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Loh, N. Y., Minchin, J. E. N., Pinnick, K. E., Verma, M., Todorčević, M., Denton, N., … Christodoulides, C. (2020). RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro. Nat Commun, 11(1), 2797. https://doi.org/10.1038/s41467-020-16592-z
Loh, Nellie Y., James E. N. Minchin, Katherine E. Pinnick, Manu Verma, Marijana Todorčević, Nathan Denton, Julia El-Sayed Moustafa, et al. “RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro.Nat Commun 11, no. 1 (June 3, 2020): 2797. https://doi.org/10.1038/s41467-020-16592-z.
Loh NY, Minchin JEN, Pinnick KE, Verma M, Todorčević M, Denton N, et al. RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro. Nat Commun. 2020 Jun 3;11(1):2797.
Loh, Nellie Y., et al. “RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro.Nat Commun, vol. 11, no. 1, June 2020, p. 2797. Pubmed, doi:10.1038/s41467-020-16592-z.
Loh NY, Minchin JEN, Pinnick KE, Verma M, Todorčević M, Denton N, Moustafa JE-S, Kemp JP, Gregson CL, Evans DM, Neville MJ, Small KS, McCarthy MI, Mahajan A, Rawls JF, Karpe F, Christodoulides C. RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro. Nat Commun. 2020 Jun 3;11(1):2797.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 3, 2020

Volume

11

Issue

1

Start / End Page

2797

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Wnt Signaling Pathway
  • Waist-Hip Ratio
  • Thrombospondins
  • Stem Cells
  • Sex Characteristics
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Mutation