2. Academic Validation
  3. 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

  • Peptides. 2022 May;151:170763. doi: 10.1016/j.peptides.2022.170763.
Md Nurul Islam 1,  Weidong Zhang 1,  Katsuya Sakai 2,  Yuki Nakazato 2,  Ryota Tanida 3,  Hideyuki Sakoda 1,  Toshiki Takei 4,  Toshifumi Takao 4,  Masamitsu Nakazato 5
Affiliations

Affiliations

  • 1 Department of Bioregulatory Sciences, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
  • 2 Division of Neurology, Respirology, Endocrinology, and Metabolism, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
  • 3 Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Ishikawa 920-8640, Japan.
  • 4 Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
  • 5 Division of Interactive Organ Systems, Department of Projects Research, Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan; AMED-CREST, Agency for Medical Research and Development, Tokyo 100-0004, Japan. Electronic address: nakazato@med.miyazaki-u.ac.jp.
PMID: 35151767 DOI: 10.1016/j.peptides.2022.170763
Abstract

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.

Keywords

Anamorelin; Blood glucose; Body temperature; GHSR; Ghrelin; JMV2959; LEAP2; [D-Lys(3)]-GHRP-6.

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