Liver-expressed antimicrobial peptide 2 functions independently of growth hormone secretagogue receptor in calorie-restricted mice
Liver-expressed antimicrobial peptide 2 functions independently of growth hormone secretagogue receptor in calorie-restricted mice
复制标题
DOI：
10.1016/j.peptides.2022.170763
复制
发表时间：
2022-02-12
期刊：
影响因子：
3
通讯作者：
Nakazato, Masamitsu
中科院分区：
文献类型：
--
作者：
Islam, Md Nurul;Zhang, Weidong;Nakazato, Masamitsu
Ghrelin是一种胃源性多肽，可刺激进食、血糖升高、体温下降和生长激素(GH)分泌。肝表达抗菌肽2(Leap2)是Ghrelin受体的内源性拮抗剂，又称生长激素促分泌素受体(GHSR)。我们研究了Leap2对C57BL/6J小鼠和GHSR基因敲除(GHSR-KO)小鼠的摄食、体重、血糖、体温和肝脏炎症相关基因的影响。我们发现，在禁食24小时的C57BL/6J小鼠或GHSR-KO小鼠中，单次注射Leap2并不能取消禁食诱导的食物摄取。此外，连续给自由喂养6天的小鼠服用Leap2不会影响摄食、体温、血浆Ghrelin或血糖。相比之下，连续给予热量限制的C57BL/6J小鼠和GHSR-KO小鼠Leap2可导致体重减轻、低血糖、体温下降，并上调肝脏中IL-6和IL-1β的mRNAs。我们的发现表明，Leap2的功能独立于GHSR，这意味着Leap2影响的生理学超越了Ghrelin-GHSR系统。
Ghrelin is a gastric-derived peptide that stimulates feeding, blood glucose elevation, body temperature reduction, and growth hormone (GH) secretion. Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous antagonist of the ghrelin receptor, also called growth hormone secretagogue receptor (GHSR). We studied the effects of LEAP2 administration on feeding, body weight, glycemia, body temperature, and inflammation-related genes in the liver in C57BL/6 J mice and Ghsr-knockout (Ghsr-KO) mice. We found that a single administration of LEAP2 did not abolish fasting-induced food intake in 24-h fasted C57BL/6 J mice or Ghsr-KO mice. Moreover, continuous LEAP2 administration to mice fed ad libitum for 6 days did not affect feeding, body temperature, plasma ghrelin, or blood glucose. By contrast, continuous LEAP2 administration to calorie-restricted C57BL/6 J mice and Ghsr-KO mice induced body weight loss, hypoglycemia, body temperature reduction, and upregulation of Il-6 and Il-1 beta mRNAs in the liver. Our findings suggest that LEAP2 functions independently of GHSR, implying that LEAP2 affects physiology beyond the ghrelin-GHSR system.