Reduced endothelial leptin signaling increases vascular adrenergic reactivity in a mouse model of congenital generalized lipodystrophy

Thiago Bruder-Nascimento, Taylor C. Kress, Matthew Pearson, Weiqin Chen, Simone Kennard, Eric J.Belin de Chantemèle

Research output: Contribution to journalArticlepeer-review

Abstract

The adipokine leptin, which is best-known for its role in the control of metabolic function, is also a master regulator of cardiovascular function. While leptin has been approved for the treatment of metabolic disorders in patients with congenital generalized lipodystrophy (CGL), the effects of chronic leptin deficiency and the treatment on vascular contractility remain unknown. Herein, we investigated the effects of leptin deficiency and treatment (0.3 mg/day/7 days) on aortic contractility in male Berardinelli-Seip 2 gene deficient mice (gBscl2-/-, model of CGL) and their wild-type control (gBscl2+/+ ), as well as in mice with selective deficiency in endothelial leptin receptor (LepREC-/- ). Lipodystrophy selectively increased vascular adrenergic contractility via NO-independent mechanisms and induced hypertrophic vascular remodeling. Leptin treatment and Nox1 inhibition blunted adrenergic hypercontractility in gBscl2-/- mice, however, leptin failed to rescue vascular media thickness. Selective deficiency in endothelial leptin receptor did not alter baseline adrenergic contractility but abolished leptin-mediated reduction in adrenergic contractility, supporting the contribution of endothelium-dependent mechanisms. These data reveal a new direct role for endothelial leptin receptors in the control of vascular contractility and homeostasis, and present leptin as a safe therapy for the treatment of vascular disease in CGL.

Original languageEnglish (US)
Article number10596
JournalInternational journal of molecular sciences
Volume22
Issue number19
DOIs
StatePublished - Oct 1 2021

Keywords

  • Adipose tissue
  • Leptin
  • Lipodystrophy
  • Vascular function

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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