C-type natriuretic peptide as a new regulator of food intake and energy expenditure.
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.
Inuzuka
Megumi
M
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Tamura
Naohisa
N
Yamada
Nobuko
N
Katsuura
Goro
G
Oyamada
Naofumi
N
Taura
Daisuke
D
Sonoyama
Takuhiro
T
Fukunaga
Yasutomo
Y
Ohinata
Kousaku
K
Sone
Masakatsu
M
Nakao
Kazuwa
K
D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000235:genetics*; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009638:Norepinephrine / Q000652:urine; D009928:Organ Specificity / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D009478:Neuropeptide Y; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D020098:Natriuretic Peptide, C-Type; D006162:Guanylate Cyclase; D009638:Norepinephrine