Hypothalamic PDE3B deficiency alters body weight and glucose homeostasis in mouse.
Hypothalamic PDE3B deficiency alters body weight and glucose homeostasis in mouse.
复制标题
DOI：
10.1530/joe-18-0304
复制
发表时间：
2018-10-01
期刊：
影响因子：
--
通讯作者：
Sahu A
中科院分区：
文献类型：
--
作者：
Sahu M;Anamthathmakula P;Sahu A
药理学研究表明，下丘脑磷酸二酯酶-3B介导瘦素和胰岛素在调节能量平衡中的作用。尽管Pde3b基因缺失的小鼠表现出能量平衡的改变，但尚不清楚这是否是由于下丘脑中Pde3b的消融。因此，为了阐明下丘脑磷酸二酯酶-3B的功能意义，我们使用Pde3bFlox/Flox和Nkx2.1-Cre小鼠产生了Pde3bNkx2.1KD小鼠，其下丘脑磷酸二酯酶-3B的表达降低了50%。为了确定部分切除下丘脑磷酸二酯酶-3B对能量和葡萄糖稳态的影响，对雄性和雌性大鼠进行了19-21周的低脂或高脂饮食。只有雌性而不是雄性的Pde3bNkx2.1KD小鼠在低脂饮食下显示出体重在13周后增加，食物摄入量增加，脂肪垫重量减少，并出现低血浆蛋白血症。高脂饮食喂养的雄性Pde3bNkx2.1KD小鼠的葡萄糖耐量得到改善，并伴随着肝脏中磷酸烯醇式丙酮酸羧激酶-1和葡萄糖-6-磷酸酶mRNA水平的降低。此外，在低脂饮食下，雄性Pde3bNkx2.1KD小鼠的胰岛素敏感性也增加了。体重或血糖稳态的变化与下丘脑前阿片黑素皮质素、神经肽Y和刺鼠相关肽mRNA水平的任何变化无关。这些结果表明，下丘脑中磷酸二酯酶-3B的部分缺失在体重和血糖稳态方面产生了性别特异性的反应，并至少部分支持了下丘脑磷酸二酯酶-3B在调节小鼠能量和葡萄糖稳态中的作用。
Pharmacological studies have suggested hypothalamic phosphodiesterase-3B to mediate leptin and insulin action in regulation of energy homeostasis. Whereas Pde3b-null mice show altered energy homeostasis, it is unknown whether this is due to ablation of Pde3b in the hypothalamus. Thus to address the functional significance of hypothalamic phosphodiesterase-3B, we used Pde3bflox/flox and Nkx2.1-Cre mice to generate Pde3bNkx2.1KD mice that showed 50% reduction of phosphodiesterase-3B in the hypothalamus. To determine the effect of partial ablation of phosphodiesterase-3B in the hypothalamus on energy and glucose homeostasis, males and females were subjected to either a low- or high-fat diet for 19-21 weeks. Only female but not male Pde3bNkx2.1KD mice on the low-fat diet showed increased body weight from 13 weeks onward with increased food intake, decreased fat pad weights and hypoleptinemia. Glucose tolerance was improved in high-fat diet-fed male Pde3bNkx2.1KD mice in association with decreased phosphoenolpyruvate carboxykinase-1 and glucose-6-phosphatase mRNA levels in the liver. Also, insulin sensitivity was increased in male Pde3bNkx2.1KD mice on the low-fat diet. Changes in body weight or in glucose homeostasis were not associated with any alteration in hypothalamic proopiomelanocortin, neuropepide Y and agouti-related peptide mRNA levels. These results suggest that partial loss of phosphodiesterase-3B in the hypothalamus produces a sex-specific response in body weight and glucose homeostasis, and support a role, at least in part, for hypothalamic phosphodiesterase-3B in regulation of energy and glucose homeostasis in mice.
影响因子：
2.5
作者：
Sahu M;Litvin DG;Sahu A
通讯作者：
Sahu A