Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Adhesion Molecules / metabolism
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Cyclic GMP / metabolism*
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Cyclic GMP-Dependent Protein Kinases / metabolism
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Diet, High-Fat / adverse effects
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Gastrointestinal Hormones / genetics
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Gastrointestinal Hormones / metabolism*
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Immunohistochemistry
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Inflammation Mediators / metabolism
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Intra-Abdominal Fat / enzymology
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Intra-Abdominal Fat / immunology
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Intra-Abdominal Fat / metabolism*
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Intra-Abdominal Fat / pathology
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Macrophages, Peritoneal / enzymology
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / metabolism*
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Macrophages, Peritoneal / pathology
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Male
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Microfilament Proteins / metabolism
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Natriuretic Peptides / genetics
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Natriuretic Peptides / metabolism*
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Obesity / etiology
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Obesity / immunology
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Obesity / metabolism
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Obesity / pathology
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Panniculitis, Peritoneal / etiology
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Panniculitis, Peritoneal / immunology
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Panniculitis, Peritoneal / metabolism*
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Panniculitis, Peritoneal / pathology
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Processing, Post-Translational
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Random Allocation
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Rats
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Rats, Transgenic
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Receptors, Enterotoxin
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Receptors, Guanylate Cyclase-Coupled / agonists*
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Receptors, Guanylate Cyclase-Coupled / genetics
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Receptors, Guanylate Cyclase-Coupled / metabolism
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Receptors, Peptide / agonists*
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Receptors, Peptide / genetics
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Receptors, Peptide / metabolism
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Second Messenger Systems*
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Vasodilator-Stimulated Phosphoprotein
Substances
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Cell Adhesion Molecules
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Gastrointestinal Hormones
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Inflammation Mediators
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Microfilament Proteins
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Natriuretic Peptides
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Phosphoproteins
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Receptors, Peptide
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Vasodilator-Stimulated Phosphoprotein
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guanylin
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Cyclic GMP-Dependent Protein Kinases
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Receptors, Enterotoxin
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Receptors, Guanylate Cyclase-Coupled
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Cyclic GMP