title: Brain-specific natriuretic peptide receptor-B deletion attenuates high-fat diet-induced visceral and hepatic lipid deposition in mice.
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.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: yui_y@kuhp.kyoto-u.ac.jp.
authors.forename: Yui
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University, School of Medicine, 35, Shinano-machi, Shinjyuku-ku, Tokyo 160-8582, Japan. Electronic address: nyamadagoto@keio.jp.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Yamada-Goto
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Katsuura
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ochi
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Division of Food Science and Biotechnology, Kyoto University Graduate School of Agriculture, Gokasyo, Uji-shi, Kyoto 611-0011, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kuwahara
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Naotetsu
authors.initials: N
authors.lastname: Kanamoto
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yasoda
authors.affiliation: Division of Food Science and Biotechnology, Kyoto University Graduate School of Agriculture, Gokasyo, Uji-shi, Kyoto 611-0011, Japan.
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Kyoto University Graduate School of Medicine Medical Innovation Center, 53, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D007031:Hypothalamus / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000737:chemistry / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015430:Weight Gain / Q000235:genetics
chemical_list: D018955:CD36 Antigens; D011506:Proteins; D012333:RNA, Messenger; C058930:brain natriuretic peptide receptor; C525805:fat-specific protein 27, mouse; D020098:Natriuretic Peptide, C-Type; D000217:Acyltransferases; C021802:2-acylglycerol O-acyltransferase; D017461:Receptors, Atrial Natriuretic Factor
keywords: Guanylyl cyclase; Hepatic steatosis; Natriuretic peptide; Obesity; Visceral fat