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

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 (<i>Oscillospiraceae</i> UCG-005, <i>Parabacteroides</i> and <i>Oscillospiraceae</i> 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 <i>MCT-1</i> and <i>mTOR</i>, and it up-regulated the mRNA expression of <i>HDAC1</i>, <i>FOXO1</i> and <i>Beclin-1</i>. 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.