C-Type Natriuretic Peptide as a New Regulator of Food Intake and Energy Expenditure

• Published in: Endocrinology (Philadelphia) 2010-08, Vol.151 (8), p.3633-3642
• Main Authors: Inuzuka, Megumi, Tamura, Naohisa, Yamada, Nobuko, Katsuura, Goro, Oyamada, Naofumi, Taura, Daisuke, Sonoyama, Takuhiro, Fukunaga, Yasutomo, Ohinata, Kousaku, Sone, Masakatsu, Nakao, Kazuwa
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose tissue (brown); Agouti-Related Protein - genetics; Agouti-Related Protein - metabolism; Animals; Appetite Regulation - drug effects; Appetite Regulation - genetics; Blood levels; Body fat; Body Temperature - drug effects; Body Temperature - genetics; Body weight; Bone dysplasia; C-Type natriuretic peptide; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Energy expenditure; Energy metabolism; Energy Metabolism - drug effects; Energy Metabolism - genetics; Food; Food intake; Gene expression; Gene Expression Regulation - drug effects; Glucose tolerance; Guanylate cyclase; Guanylate Cyclase - genetics; Guanylate Cyclase - metabolism; Injections, Intraventricular; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Natriuretic Peptide, C-Type - administration & dosage; Natriuretic Peptide, C-Type - genetics; Natriuretic Peptide, C-Type - metabolism; Natriuretic Peptide, C-Type - physiology; Neuropeptide Y - genetics; Neuropeptide Y - metabolism; Norepinephrine - urine; Organ Specificity - genetics; Oxygen consumption; Peptides; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phenotypes; PPAR gamma - genetics; PPAR gamma - metabolism; Propranolol; Protein folding; Skeleton; Tissue Distribution; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2010-0141

The physiological implication of C-type natriuretic peptide (CNP) including energy metabolism has not been elucidated, because of markedly short stature in CNP-null mice. In the present study we analyzed food intake and energy expenditure of CNP-null mice with chondrocyte-targeted CNP expression (CNP-Tg/Nppc−/− mice), in which marked skeletal dysplasia was rescued, to investigate the significance of CNP under minimal influences of skeletal phenotypes. In CNP-Tg/Nppc−/− mice, body weight and body fat ratio were reduced by 24% and 32%, respectively, at 20 wk of age, and decreases of blood glucose levels during insulin tolerance tests were 2-fold exaggerated at 17 wk of age, as compared with CNP-Tg/Nppc+/+ mice. Urinary noradrenalin excretion of CNP-Tg/Nppc−/− mice was greater than that of CNP-Tg/Nppc+/+ mice by 28%. In CNP-Tg/Nppc−/− mice, rectal temperature at 1600 h was higher by 1.1 C, and uncoupling protein-1 mRNA expression in the brown adipose tissue was 2-fold increased, which was canceled by propranolol administration, as compared with CNP-Tg/Nppc+/+ mice. Oxygen consumption was significantly increased in CNP-Tg/Nppc−/− mice compared with that in CNP-Tg/Nppc+/+ mice. Food intake of CNP-Tg/Nppc−/− mice upon ad libitum feeding and refeeding after 48 h starvation were reduced by 21% and 61%, respectively, as compared with CNP-Tg/Nppc+/+ mice. This study unveiled a new aspect of CNP as a molecule regulating food intake and energy expenditure. Further analyses on precise mechanisms of CNP actions would lead to the better understanding of the significance of the CNP/guanylyl cyclase-B system in food intake and energy expenditure. C-type natriuretic peptide is a new regulator of energy homeostasis and participates in body fat accumulation by inhibiting sympathetic nervous system activity and energy expenditure.