Rabbit Anti-Human GPRC6A (internal) Polyclonal antibody

Simple Summary Insect powders, includingTenebrio molitor(TM),Musca domesticalarvae (MDL) andZophobas morio(ZM), as high-quality and renewable protein sources are commonly applied in livestock and poultry feed production. The molecular effect of insect protein on amino acid metabolism in pigs needs to be explored. We found that insect powder as a protein source in feed regulated the mTOR signal pathway and improved amino acid transportation in the intestine for growth promotion. Insect powder may be a potentially promising protein source for pig production. This study was conducted to evaluate the effects of dietary insect powder supplementation as a protein source on plasma amino acid profiles, intestinal amino acid transport and sensing in a piglet model. A total of 144 weanling piglets were randomly assigned to four experimental diets for two phases (Days 1-28 and Days 29-56), to assess the effects on amino acid profiles and transportation in the segments of the intestine. The groups were basal diet (control), control diet plusTenebrio molitor(TM), control diet plusMusca domesticalarvae (MDL) and control diet plusZophobas morio(ZM). The plasma free amino acid levels were stable comparable among treatments, except that the lysine level was significantly reduced by dietary MDL and ZM supplementation in the first phase (p< 0.05). In the 1st phase, the sensitivity of intestinal segments to the regulation of the amino acid level by insect powder supplementation follows sequence: colon > ileum > jejunum, while the order switched to jejunum > colon > ileum in the 2nd phase. The relative RNA expressions of mitogen-activated protein 4 kinase 3 (MAP4K3), sodium dependent neutral amino acid transporter2 (SNAT2), the transient receptor potential cation channel subfamily V member 1 (TRPV1) and taste 1 receptor member 1/3 (T1R3) in the segments of the intestine were affected by different dietary insect powder supplementation. G protein-coupled receptor family C group 6 member A (GPRC6A) level in the jejunal and colonic mucosa was upregulated by MDL supplementation (p< 0.05). These results indicated that dietary insects improved the metabolism of the amino acid in the prophase (the 1st phase) through regulating the sensing gene and mTOR signal pathway in intestinal mucosa by targeting different receptors. The finding demonstrates that the insect powder is a potentially promising source for protein deposition.

Background & Aims: 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. Methods: 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. Results: 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 absorption, mediated by the 5'AMP-activated protein kinase pathway. In addition, glucagon like peptide-1 secretion was induced by MTL treatment. Conclusions: Oral or intraperitoneal MTL significantly improves the symptoms of NAFLD by inhibiting lipid absorption and insulin resistance. MTL could be a potential therapeutic candidate for the treatment of NAFLD. Lay summary: A novel murine peptide hormone, herein named 'metabolitin', inhibits fatty acid absorption and improves systemic insulin resistance in a murine model of obesity and non-alcoholic fatty liver disease. Thus, metabolitin has therapeutic potential for the treatment of patients with non-alcoholic fatty liver disease. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.