Guanylin-Guanylyl cyclase-C signaling in macrophages regulates mesenteric fat inflammation induced by high-fat diet

Endocrine Journal

Yukari Date¹  Yurie Fujii¹  Cho-Rong Bae²  Sayaka Akieda-Asai¹  Masahiro Yasuda³  Kazuya Hasegawa¹ 

[1]Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan

[2]Department of Food Science and Human Nutrition, Obesity Research Center, Chonbuk National University, Jeonju 561-756, Korea

[3]Department of Veterinary Anatomy, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan

关键词: cGMP;    High-fat diet;    PKG;    Proinflammatory factor;    VASP;   

DOI  :  10.1507/endocrj.EJ15-0193

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(28)Guanylin (Gn), a bioactive peptide, and its receptor, guanylyl cyclase-C (GC-C), are primarily present in the intestine and maintain homeostasis in body fluids.Recently, rats whose macrophages overexpress Gn and GC-C were found to be resistant to diet-induced obesity.Considering that obesity is strongly related to a chronic inflammatory state in white adipose tissues, it is possible that Gn-GC-C macrophages contribute to the regulation of inflammation.In the present study, we investigated the inflammatory state of mesenteric fat in rats transgenic for both Gn and GC-C (double-transgenic [dTg] rats) by evaluating the levels of cyclic guanosine monophosphate (cGMP), a second messenger of Gn-GC-C, cGMP-dependent protein kinase (PKG), and phosphorylated vasodilator-stimulated phosphoprotein (VASP), a target protein of PKG.The levels of cGMP in dTg rats was higher than in WT rats fed the same diet.Although there were no significant differences in levels of PKG and phosphorylated VASP between WT and dTg rats fed a standard diet (STD), these levels in dTg rats fed a high fat diet (HFD) were markedly increased compared with levels in HFD WT rats.Furthermore, mRNA levels of proinflammatory factors in mesenteric fat were lower in HFD dTg rats than in HFD WT rats and were similar to levels in STD WT and dTg rats.These results indicate that the Gn-GC-C system in macrophages regulates the cGMP-PKG-VASP pathway and controls obesity through the downregulation of proinflammatory factors.

【 授权许可】

Unknown