Brain-specific natriuretic peptide receptor-B deletion attenuates high-fat diet-induced visceral and hepatic lipid deposition in mice

Yui Yamashita, Nobuko Yamada-Goto, Goro Katsuura, Yukari Ochi, Yugo Kanai, Yuri Miyazaki, Koichiro Kuwahara, Naotetsu Kanamoto, Masako Miura, Akihiro Yasoda, Kousaku Ohinata, Nobuya Inagaki, Kazuwa Nakao

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

C-type natriuretic peptide (CNP) and its receptor, natriuretic peptide receptor-B (NPR-B), are abundantly distributed in the hypothalamus. To explore the role of central CNP/NPR-B signaling in energy regulation, we generated mice with brain-specific NPR-B deletion (BND mice) by crossing Nestin-Cre transgenic mice and mice with a loxP-flanked NPR-B locus. Brain-specific NPR-B deletion prevented body weight gain induced by a high-fat diet (HFD), and the mesenteric fat and liver weights were significantly decreased in BND mice fed an HFD. The decreased liver weight in BND mice was attributed to decreased lipid accumulation in the liver, which was confirmed by histologic findings and lipid content. Gene expression analysis revealed a significant decrease in the mRNA expression levels of CD36, Fsp27, and Mogat1 in the liver of BND mice, and uncoupling protein 2 mRNA expression was significantly lower in the mesenteric fat of BND mice fed an HFD than in that of control mice. This difference was not observed in the epididymal or subcutaneous fat. Although previous studies reported that CNP/NPR-B signaling inhibits SNS activity in rodents, SNS is unlikely to be the underlying mechanism of the metabolic phenotype observed in BND mice. Taken together, CNP/NPR-B signaling in the brain could be a central factor that regulates visceral lipid accumulation and hepatic steatosis under HFD conditions. Further analyses of the precise mechanisms will enhance our understanding of the contribution of the CNP/NPR-B system to energy regulation.

Original languageEnglish
Pages (from-to)38-50
Number of pages13
JournalPeptides
Volume81
DOIs
Publication statusPublished - 2016 Jul 1

Keywords

  • Guanylyl cyclase
  • Hepatic steatosis
  • Natriuretic peptide
  • Obesity
  • Visceral fat

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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