RAMP1 and RAMP3 Differentially Control Amylin's Effects on Food Intake, Glucose and Energy Balance in Male and Female Mice.,Neuroscience

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RAMP1 and RAMP3 Differentially Control Amylin's Effects on Food Intake, Glucose and Energy Balance in Male and Female Mice.
Neuroscience ( IF 2.9 ) Pub Date : 2019-12-24 , DOI: 10.1016/j.neuroscience.2019.11.036
Bernd Coester ₁ , Sydney W Pence ₁ , Soraya Arrigoni ₁ , Christina N Boyle ₁ , Christelle Le Foll ₁ , Thomas A Lutz ₁

Affiliation

Amylin is a pancreatic peptide, which acts as a key controller of food intake and energy balance and predominately binds to three receptors (AMY 1-3). AMY 1-3 are composed of a calcitonin core receptor (CTR) and associated receptor-activity modifying proteins (RAMPs) 1-3. Using RAMP1, RAMP3 and RAMP1/3 global KO mice, this study aimed to determine whether the absence of one or two RAMP subunits affects food intake, glucose homeostasis and metabolism. Of all the RAMP-deficient mice, only high-fat diet fed RAMP1/3 KO mice had increased body weight. Chow-fed RAMP3 KO and high-fat diet fed 1/3 KO male mice were glucose intolerant. Fat depots were increased in RAMP1 KO male mice. No difference in energy expenditure was observed but the respiratory exchange ratio (RER) was elevated in RAMP1/3 KO. RAMP1 and 1/3 KO male mice displayed an increase in intermeal interval (IMI) and meal duration, whereas IMI was decreased in RAMP3 KO male and female mice. WT and RAMP1, RAMP3, and RAMP1/3 KO male and female littermates were then assessed for their food intake response to an acute intraperitoneal injection of amylin or its receptor agonist, salmon calcitonin (sCT). RAMP1/3 KO were insensitive to both, while RAMP3 KO were responsive to sCT only and RAMP1 KO to amylin only. While female mice generally weighed less than male mice, only RAMP1 KO showed a clear sex difference in meal pattern and food intake tests. Lastly, a decrease in CTR fibers did not consistently correlate with a decrease in amylin- induced c-Fos expression in the area postrema (AP). Ultimately, the results from this study provide evidence for a role of RAMP1 in mediation of fat utilization and a role for RAMP3 in glucose homeostasis and amylin's anorectic effect.

中文翻译：

RAMP1 和 RAMP3 不同地控制糊精对雄性和雌性小鼠食物摄入、葡萄糖和能量平衡的影响。

胰淀素是一种胰肽，它是食物摄入和能量平衡的关键控制器，主要与三种受体 (AMY 1-3) 结合。AMY 1-3 由降钙素核心受体 (CTR) 和相关的受体活性修饰蛋白 (RAMP) 1-3 组成。本研究使用 RAMP1、RAMP3 和 RAMP1/3 全局 KO 小鼠，旨在确定一个或两个 RAMP 亚基的缺失是否会影响食物摄入、葡萄糖稳态和新陈代谢。在所有 RAMP 缺陷小鼠中，只有高脂饮食喂养的 RAMP1/3 KO 小鼠体重增加。喂食 RAMP3 KO 和喂食 1/3 KO 雄性小鼠的高脂肪饮食是葡萄糖不耐受的。RAMP1 KO 雄性小鼠的脂肪库增加。没有观察到能量消耗的差异，但 RAMP1/3 KO 中的呼吸交换率 (RER) 升高。RAMP1 和 1/3 KO 雄性小鼠的中间间隔 (IMI) 和进餐时间增加，而 RAMP3 KO 雄性和雌性小鼠的 IMI 减少。然后评估 WT 和 RAMP1、RAMP3 和 RAMP1/3 KO 雄性和雌性同窝仔猪对急性腹腔注射胰淀素或其受体激动剂鲑鱼降钙素 (sCT) 的食物摄入反应。RAMP1/3 KO 对两者都不敏感，而 RAMP3 KO 仅对 sCT 有反应，而 RAMP1 KO 仅对胰淀素有反应。虽然雌性小鼠的体重通常低于雄性小鼠，但只有 RAMP1 KO 在膳食模式和食物摄入测试中显示出明显的性别差异。最后，CTR 纤维的减少与极区 (AP) 中糊精诱导的 c-Fos 表达的减少并不一致。最终，

更新日期：2019-12-24

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