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Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor‐Mediated PKA Pathway
Author(s) -
Dai HangBing,
Wang FangZheng,
Kang Ying,
Sun Jing,
Zhou Hong,
Gao Qing,
Li ZhenZhen,
Qian Pei,
Zhu GuoQing,
Zhou YeBo
Publication year - 2021
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.23012
Subject(s) - adrenomedullin , medicine , endocrinology , inflammation , adipose tissue , white adipose tissue , receptor , protein kinase a , nitric oxide synthase , chemistry , nitric oxide , kinase , biochemistry
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.