Liver-expressed antimicrobial peptide 2 functions independently of growth hormone secretagogue receptor in calorie-restricted mice.

Md Nurul Islam, Weidong Zhang, Katsuya Sakai, Yuki Nakazato, Ryota Tanida, Hideyuki Sakoda, Toshiki Takei, Toshifumi Takao, Masamitsu Nakazato

Peptides 2022 May

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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-1β mRNAs in the liver. Our findings suggest that LEAP2 functions independently of GHSR, implying that LEAP2 affects physiology beyond the ghrelin-GHSR system. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Md Nurul Islam, Weidong Zhang, Katsuya Sakai, Yuki Nakazato, Ryota Tanida, Hideyuki Sakoda, Toshiki Takei, Toshifumi Takao, Masamitsu Nakazato. Liver-expressed antimicrobial peptide 2 functions independently of growth hormone secretagogue receptor in calorie-restricted mice. Peptides. 2022 May;151:170763