Involvement of guanylin and GC-C in rat mesenteric macrophages in resistance to a high-fat diet

Sayaka Akieda-Asai, Masako Sugiyama, Takashi Miyazawa, Shuichi Koda, Ichiro Okano, Kazuyo Senba, Paul Emile Poleni, Yoshiyuki Hizukuri, Atsushi Okamoto, Kenichi Yamahara, Eri Mutoh, Fumiyo Aoyama, Akira Sawaguchi, Mayumi Furuya, Mikiya Miyazato, Kenji Kangawa, Yukari Date

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


A high-fat diet (HFD) is a well-known contributing factor in the development of obesity. Most rats fed HFDs become obese. Those that avoid obesity when fed HFDs are considered diet resistant (DR). We performed a microarray screen to identify genes specific to the mesenteric fat of DR rats and revealed high expression of guanylin and guanylyl cyclase C (GC-C) in some subjects. Our histologic studies revealed that the cellular source of guanylin and GC-C is macrophages. Therefore, we developed double-transgenic (Tg) rats overexpressing guanylin and GC-C in macrophages and found that they were resistant to the effects of HFDs. In the mesenteric fat of HFD-fed Tg rats, Fas and perilipin mRNAs were downregulated, and those of genes involved in fatty acid oxidation were upregulated, compared with the levels in HFD-fed wild-type rats. In vitro studies demonstrated that lipid accumulation was markedly inhibited in adipocytes cocultured with macrophages expressing guanylin and GC-C and that this inhibition was reduced after treatment with guanylin- and GC-C-specific siRNAs. Our results suggest that the macrophagic guanylin-GC-C system contributes to the altered expression of genes involved in lipid metabolism, leading to resistance to obesity.

Original languageEnglish
Pages (from-to)85-96
Number of pages12
JournalJournal of Lipid Research
Issue number1
Publication statusPublished - Jan 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology


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