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Obesity Inhibits Angiogenesis Through TWIST1-SLIT2 Signaling

Tendai Hunyenyiwa1,2, Kathryn Hendee1, Kienna Matus1

  • 1Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States.

Frontiers in Cell and Developmental Biology
|October 18, 2021
PubMed

Insights

Obesity impairs blood vessel formation in adipose tissue by reducing TWIST1 and SLIT2 signaling in endothelial cells (ECs). Restoring TWIST1 levels can improve angiogenesis in obese adipose tissue.

Area of Science:

  • Endocrinology
  • Vascular Biology
  • Cell Biology

Background:

  • Angiogenesis is crucial for adipose tissue function, but it is impaired in obese individuals.
  • The precise mechanisms inhibiting angiogenesis in obese adipose tissue remain unclear.
  • TWIST1 is a transcription factor known to regulate angiogenesis and vascular function.

Purpose of the Study:

  • To investigate the role of TWIST1-SLIT2 signaling in the inhibition of angiogenesis in obese human adipose tissue.
  • To elucidate the molecular mechanisms underlying impaired vascularization in obesity.

Main Methods:

  • Isolation and culture of endothelial cells (ECs) from lean and obese human adipose tissues.
  • Manipulation of TWIST1 expression (knockdown and overexpression) in ECs.
  • Assessment of SLIT2 expression, EC DNA synthesis, and cell migration.
  • In vivo assessment of blood vessel formation using subcutaneous implantation in mice.

Main Results:

  • TWIST1 and SLIT2 levels are significantly lower in ECs from obese adipose tissue compared to lean controls.
  • TWIST1 regulates SLIT2 expression; TWIST1 knockdown reduces SLIT2, while TWIST1 overexpression restores it.
  • Obese ECs exhibit reduced DNA synthesis and migration, which are rescued by TWIST1 overexpression.
  • In vivo, obese ECs impair blood vessel formation, an effect reversed by SLIT2 or TWIST1-overexpressing ECs.

Conclusions:

  • Obesity impairs adipose tissue angiogenesis via a mechanism involving reduced TWIST1-SLIT2 signaling in endothelial cells.
  • TWIST1-SLIT2 pathway represents a potential therapeutic target for improving adipose tissue vascularization in obesity.
Keywords:
SLIT2TWIST1adipose tissueangiogenesisobesity

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