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

Endocrinology - Tập 151 Số 8 - Trang 3633-3642 - 2010
Megumi Inuzuka1, Naohisa Tamura1, Nobuko Yamada1, Goro Katsuura1, Naofumi Oyamada1, Daisuke Taura1, Takuhiro Sonoyama1, Yasutomo Fukunaga1, Kousaku Ohinata2, Masakatsu Sone1, Kazuwa Nakao1
1Department of Medicine and Clinical Science (M.I., N.T., N.Y., G.K., N.O., D.T., T.S., Y.F., M.S., K.N.), Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;
2Division of Food Science and Biotechnology (K.O.), Kyoto University Graduate School of Agriculture, Kyoto 611-0011, Japan

Tóm tắt

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.

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