1. Involvement of guanylin and GC-C in rat mesenteric macrophages in resistance to a high-fat diet
- Author
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Paul Emile Poleni, Eri Mutoh, Takashi Miyazawa, Atsushi Okamoto, Kazuyo Senba, Kenichi Yamahara, Yukari Date, Ichiro Okano, Mayumi Furuya, Shuichi Koda, Kenji Kangawa, Mikiya Miyazato, Akira Sawaguchi, Yoshiyuki Hizukuri, Masako Sugiyama, Fumiyo Aoyama, and Sayaka Akieda-Asai
- Subjects
Male ,obesity ,medicine.medical_specialty ,Receptors, Peptide ,Guanylin ,diet resistance ,Receptors, Enterotoxin ,QD415-436 ,Fatty Acids, Nonesterified ,Biology ,Diet, High-Fat ,Biochemistry ,dietary lipids ,Gastrointestinal Hormones ,chemistry.chemical_compound ,Endocrinology ,Downregulation and upregulation ,Internal medicine ,lipid metabolism ,Adipocytes ,medicine ,Animals ,Insulin ,Mesentery ,Gene Knock-In Techniques ,RNA, Messenger ,RNA, Small Interfering ,Natriuretic Peptides ,Receptor ,Beta oxidation ,Triglycerides ,Research Articles ,Cholesterol ,Macrophages ,Lipid metabolism ,Cell Biology ,Guanylate cyclase 2C ,Rats ,Gene Expression Regulation ,Liver ,Receptors, Guanylate Cyclase-Coupled ,chemistry ,Macrophages, Peritoneal ,Perilipin ,Rats, Transgenic ,Oxidation-Reduction ,hormones, hormone substitutes, and hormone antagonists - Abstract
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.
- Published
- 2013