Iturin A Rescued STb-R-Induced Pork Skeletal Muscle Growth Restriction through the Hypothalamic-Pituitary-mTORC1 Growth Axis

SIMPLE SUMMARY: Since antimicrobial peptides (AMPs) possess broad-spectrum antimicrobial activity and low drug resistance, their development as antibiotic alternatives are of interest. Previous studies reported that the performance of pigs was improved by AMPs through the protection of the intestine. Nevertheless, direct evidence linking AMPs and skeletal muscle growth is needed. In the current work, Iturin A as a novel antimicrobial peptide was selected to fight engineered STb-Rosetta Escherichia coli (STb-R) to measure pork skeletal muscle growth and further mechanisms. We found the restrictions of body weight gain and skeletal muscle growth caused by STb-R could be rescued after Iturin A gavage, and this was mediated by the hypothalamic-pituitary-Mtorc1 growth axis. ABSTRACT: The engineered STb-Rosetta Escherichia coli (STb-R) was designed to investigate the effects of Iturin A on the skeletal muscle growth of weaned piglets. A total of 28 piglets were randomly divided into 4 groups (7 piglets per group): the control group (100 mL PBS), the Iturin A group (100 mL 320 mg/kg body weight (BW) Iturin A), the STb-R group (100 mL 1 × 10(10) CFU/mL STb-R), and the Iturin A + STb-R group (100 mL 320 mg/kg BW Iturin A + 1 × 10(10) CFU/mL STb-R). Compared with the control, STb-R-reduced body weight gain were rescued by Iturin A. The semimembranosus muscle weight recovered to normal level in the Iturin A + STb-R group. The level of relevant genes of the growth axis were elevated by Iturin A, including GHRH in the hypothalamus, GHRHR and GH in the pituitary, and GHR, IGF-1 and IGF-1R in the semimembranosus muscle. Moreover, Iturin A increased the mean fiber area and the number of proliferating cells in the semimembranosus muscle, which were decreased by STb-R. Additionally, the mTORC1 pathway was reactivated by Iturin A to relieve the suppression of STb-R. Collectively, the hypothalamic-pituitary growth axis-mediated Iturin A reactivated the mTORC1 pathway to rescue STb-R-restricted pork skeletal muscle growth.