Antagonization of Ghrelin Suppresses Muscle Protein Deposition by Altering Gut Microbiota and Serum Amino Acid Composition in a Pig Model

SIMPLE SUMMARY: This study investigated the effects of the antagonization of ghrelin on muscle protein deposition, eating patterns and gut microbiota in pigs by injecting ghrelin antagonist ([D-Lys3]-GHRP-6) in a short term. We found that the antagonization of ghrelin affected the eating patterns of animals, which resulted in changes in the absorption of amino acids and gut microbiota, and it reduced protein deposition in muscles. We emphasize the important role of ghrelin in promoting muscle protein deposition and provide new clues for future research on improving muscle loss. ABSTRACT: Ghrelin is an appetite-stimulating hormone that can increase food intake and has been reported to prevent muscle loss; however, the mechanism is not yet fully understood. In this study, [D-Lys3]-GHRP-6 (GHRP) was used to investigate the effects of the antagonization of ghrelin on muscle protein deposition, eating patterns and gut microbiota in a pig model. We found that the growth performance and muscle fiber cross-sectional area of pigs treated with GHRP were significantly reduced compared with the control (CON) group. Moreover, the levels of serum isoleucine, methionine, arginine and tyrosine in the GHRP group were lower than that of the CON group. The abundance of acetate-producing bacteria (Oscillospiraceae UCG-005, Parabacteroides and Oscillospiraceae NK4A214 group) and acetate concentration in the colons of pigs treated with GHRP were significantly reduced. In addition, the injection of GHRP down-regulated the mRNA expression of MCT-1 and mTOR, and it up-regulated the mRNA expression of HDAC1, FOXO1 and Beclin-1. In summary, the antagonization of ghrelin reduced the concentration of important signal molecules (Arg, Met and Ile) that activate the mTOR pathway, concurrently reduce the concentration of HDAC inhibitors (acetate), promote autophagy and finally reduce protein deposition in muscles.