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Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue.

Publication ,  Journal Article
Minchin, JEN; Dahlman, I; Harvey, CJ; Mejhert, N; Singh, MK; Epstein, JA; Arner, P; Torres-Vázquez, J; Rawls, JF
Published in: Proc Natl Acad Sci U S A
April 7, 2015

Genome-wide association studies have implicated PLEXIN D1 (PLXND1) in body fat distribution and type 2 diabetes. However, a role for PLXND1 in regional adiposity and insulin resistance is unknown. Here we use in vivo imaging and genetic analysis in zebrafish to show that Plxnd1 regulates body fat distribution and insulin sensitivity. Plxnd1 deficiency in zebrafish induced hyperplastic morphology in visceral adipose tissue (VAT) and reduced lipid storage. In contrast, subcutaneous adipose tissue (SAT) growth and morphology were unaffected, resulting in altered body fat distribution and a reduced VAT:SAT ratio in zebrafish. A VAT-specific role for Plxnd1 appeared conserved in humans, as PLXND1 mRNA was positively associated with hypertrophic morphology in VAT, but not SAT. In zebrafish plxnd1 mutants, the effect on VAT morphology and body fat distribution was dependent on induction of the extracellular matrix protein collagen type V alpha 1 (col5a1). Furthermore, after high-fat feeding, zebrafish plxnd1 mutant VAT was resistant to expansion, and excess lipid was disproportionately deposited in SAT, leading to an even greater exacerbation of altered body fat distribution. Plxnd1-deficient zebrafish were protected from high-fat-diet-induced insulin resistance, and human VAT PLXND1 mRNA was positively associated with type 2 diabetes, suggesting a conserved role for PLXND1 in insulin sensitivity. Together, our findings identify Plxnd1 as a novel regulator of VAT growth, body fat distribution, and insulin sensitivity in both zebrafish and humans.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

April 7, 2015

Volume

112

Issue

14

Start / End Page

4363 / 4368

Location

United States

Related Subject Headings

  • Zebrafish
  • Signal Transduction
  • RNA, Messenger
  • Obesity
  • Nerve Tissue Proteins
  • Mutation
  • Mice
  • Membrane Glycoproteins
  • Lipids
  • Intracellular Signaling Peptides and Proteins
 

Citation

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Minchin, J. E. N., Dahlman, I., Harvey, C. J., Mejhert, N., Singh, M. K., Epstein, J. A., … Rawls, J. F. (2015). Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue. Proc Natl Acad Sci U S A, 112(14), 4363–4368. https://doi.org/10.1073/pnas.1416412112
Minchin, James E. N., Ingrid Dahlman, Christopher J. Harvey, Niklas Mejhert, Manvendra K. Singh, Jonathan A. Epstein, Peter Arner, Jesús Torres-Vázquez, and John F. Rawls. “Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue.Proc Natl Acad Sci U S A 112, no. 14 (April 7, 2015): 4363–68. https://doi.org/10.1073/pnas.1416412112.
Minchin JEN, Dahlman I, Harvey CJ, Mejhert N, Singh MK, Epstein JA, et al. Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4363–8.
Minchin, James E. N., et al. “Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue.Proc Natl Acad Sci U S A, vol. 112, no. 14, Apr. 2015, pp. 4363–68. Pubmed, doi:10.1073/pnas.1416412112.
Minchin JEN, Dahlman I, Harvey CJ, Mejhert N, Singh MK, Epstein JA, Arner P, Torres-Vázquez J, Rawls JF. Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4363–4368.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

April 7, 2015

Volume

112

Issue

14

Start / End Page

4363 / 4368

Location

United States

Related Subject Headings

  • Zebrafish
  • Signal Transduction
  • RNA, Messenger
  • Obesity
  • Nerve Tissue Proteins
  • Mutation
  • Mice
  • Membrane Glycoproteins
  • Lipids
  • Intracellular Signaling Peptides and Proteins