C-Type Natriuretic Peptide as a New Regulator of Food Intake and Energy Expenditure
C-Type Natriuretic Peptide as a New Regulator of Food Intake and Energy Expenditure
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DOI：
10.1210/en.2010-0141
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发表时间：
2010-08-01
期刊：
影响因子：
4.8
通讯作者：
Nakao, Kazuwa
中科院分区：
文献类型：
--
作者：
Inuzuka, Megumi;Tamura, Naohisa;Nakao, Kazuwa
由于C型利钠肽（CNP）基因敲除小鼠身材明显矮小，因此尚未阐明CNP的生理学意义（包括能量代谢）。在本研究中，我们分析了具有软骨细胞靶向CNP表达的CNP缺失小鼠（CNP-Tg/Nppc（-/-）小鼠）的食物摄入和能量消耗，其中显著的骨骼发育不良得到挽救，以研究CNP在骨骼表型影响最小的情况下的意义。与CNP-Tg/Nppc（+/+）小鼠相比，CNP-Tg/Nppc（-/-）小鼠在20周龄时体重和体脂比分别降低了24%和32%，在17周龄时胰岛素耐量试验期间血糖水平的降低被放大了2倍。CNP-Tg/Nppc（-/-）小鼠尿去甲肾上腺素排泄量比CNP-Tg/Nppc（+/+）小鼠高28%。与CNP-Tg/Nppc（-/-）小鼠相比，CNP-Tg/Nppc（-/-）小鼠1600 h直肠温度升高1.1 ℃，棕色脂肪组织中解偶联蛋白-1 mRNA表达增加2倍，但普萘洛尔可消除这种增加。与CNP-Tg/Nppc（+/+）小鼠相比，CNP-Tg/Nppc（-/-）小鼠的耗氧量显著增加。与CNP-Tg/Nppc（+/+）小鼠相比，CNP-Tg/Nppc（-/-）小鼠在自由进食和饥饿48 h后再进食时的摄食量分别减少21%和61%。这项研究揭示了CNP作为调节食物摄入和能量消耗的分子的新方面。对CNP作用的精确机制的进一步分析将导致更好地理解CNP/鸟苷酸环化酶-B系统在食物摄入和能量消耗中的意义。（内分泌学151：3633-3642，2010）
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. (Endocrinology 151: 3633-3642, 2010)