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Alamandine reduces leptin expression through the c-Src/p38 MAP kinase pathway in adipose tissue

Tsuyoshi Uchiyama1, Fumikazu Okajima2, Chihiro Mogi1

  • 1Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan.

Plos One
|June 8, 2017
PubMed
Abstract

Insights

Alamandine and angiotensin 1-7 have opposing effects on leptin in fat cells. Alamandine decreases leptin, while angiotensin 1-7 increases it, impacting obesity-related conditions.

Area of Science:

  • Endocrinology and Metabolism
  • Cardiovascular Physiology
  • Renal Physiology

Background:

  • Obesity is linked to diabetes, hypertension, and kidney dysfunction.
  • Angiotensin 1-7 and alamandine are peptide hormones in the renin-angiotensin system.
  • Alamandine levels rise with renal dysfunction, and both peptides improve cardiovascular function.

Purpose of the Study:

  • To investigate if alamandine affects leptin expression and secretion in adipocytes similarly to angiotensin 1-7.
  • To understand the differential roles of these peptides in adipose tissue regulation.

Main Methods:

  • Isolated peri-renal visceral adipose tissue and adipocytes from male Wistar rats were studied.
  • Leptin expression and secretion were measured after treatment with Angiotensin II, Angiotensin 1-7, and alamandine.
  • In vivo effects on blood leptin levels and signaling pathways (Gq, c-Src, p38 MAPK, IκB) were analyzed.

Main Results:

  • Angiotensin 1-7 (1 nM) increased leptin secretion and expression.
  • Alamandine (1 nM) decreased leptin secretion and expression in adipose tissue and adipocytes, and lowered blood leptin levels.
  • Alamandine also induced nitric oxide and plasminogen activator inhibitor 1 expression.

Conclusions:

  • Angiotensin 1-7 and alamandine exert opposing effects on leptin in adipose tissue.
  • These opposing actions in adipocytes are mediated by distinct receptors (Mas and MRGPRD), mirroring effects seen with Angiotensin II receptors.

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