Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor-Mediated PKA Pathway

Obesity (Silver Spring). 2021 Jan;29(1):86-97. doi: 10.1002/oby.23012. Epub 2020 Sep 28.

Abstract

Objective: Adrenomedullin (ADM) possesses therapeutic potential for inflammatory diseases. Consequently, the effects of ADM on inflammation in visceral white adipose tissue (vWAT) of obese rats or in adipocytes were explored in this study.

Methods: Male rats were fed a high-fat diet for 12 weeks to induce obesity, and obese rats were implanted with osmotic minipumps providing constant infusion of ADM (300 ng/kg per hour) and continued to be fed a high-fat diet for 4 weeks.

Results: When compared with the control group, endogenous protein expression of ADM and ADM receptors in vWAT and in lipopolysaccharide (LPS)-treated adipocytes was markedly increased. ADM significantly decreased the protein expression of the inflammatory mediators TNFα, IL-1β, cyclooxygenase-2, and inducible nitric oxide synthase in vWAT of obese rats and in adipocytes stimulated by LPS. It also inhibited the activation of the inflammatory signaling pathways MAPK and NF-κB induced by LPS in adipocytes. These effects of ADM in adipocytes were inhibited by the administration of ADM receptor antagonist and cAMP-dependent protein kinase (PKA) activation inhibitor.

Conclusions: ADM can inhibit inflammation in WAT in obesity, which may be mediated by the activation of ADM receptors and PKA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / metabolism
  • Adipose Tissue, White / metabolism*
  • Adrenomedullin / metabolism*
  • Animals
  • C-Reactive Protein / analysis
  • Cyclooxygenase 2 / metabolism
  • Diet, High-Fat
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Obesity / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenomedullin / antagonists & inhibitors
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / blood

Substances

  • IL1B protein, rat
  • Inflammation Mediators
  • Interleukin-1beta
  • NF-kappa B
  • Receptors, Adrenomedullin
  • Tumor Necrosis Factor-alpha
  • adrenomedullin receptor, rat
  • Adrenomedullin
  • C-Reactive Protein
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Cyclooxygenase 2
  • Ptgs2 protein, rat