Newly identified peptide hormone inhibits intestinal fat absorption and improves NAFLD through its receptor GPRC6A.

Journal of Hepatology
Bin TengPei-Gen Ren

Abstract

Circulating peptides and G protein-coupled receptors (GPCRs) have gained much attention because of their biofunctions in metabolic disorders including obesity and non-alcoholic fatty liver disease (NAFLD). Herein, we aimed to characterize the role and therapeutic potential of a newly identified peptide hormone in NAFLD. Using bioinformatics, we identified a murine circulating pentadecapeptide flanked by potential convertase cleavage sites of osteocalcin (OCN), which we named 'metabolitin (MTL)'. We used ligand-receptor binding, receptor internalization, bioluminescence resonance energy transfer and Nano isothermal titration calorimetry assays to study the binding relationship between MTL and GPRC6A. For in vivo biological studies, wild-type mice kept on a high-fat diet (HFD) were injected or gavaged with MTL to study its function in NAFLD. We confirmed that MTL binds to GPRC6A and OCN interacts with GPRC6A using in vitro biological studies. Both intraperitoneal and oral administration of MTL greatly improved NAFLD and insulin resistance in a mouse model. Interacting with GPRC6A expressed in intestines, MTL can significantly inhibit intestinal neurotensin secretion, which in turn inhibits triglyceride but not cholesterol gut abs...Continue Reading

Citations

Jul 9, 2020·Scientific Reports·Min PiL Darryl Quarles
Dec 4, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Mingfeng XiaXin Gao
Dec 20, 2020·Biochimica Et Biophysica Acta. General Subjects·Karan KapoorJeremy C Smith
Feb 4, 2021·International Journal of Endocrinology·Mingliang ZhangYuqian Bao
Feb 8, 2021·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Ilaria BarchettaMarco G Baroni
Mar 16, 2021·World Journal of Gastroenterology : WJG·Ming Yang, Chun-Ye Zhang

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