Enteral nutrition alleviated lipopolysaccharides-induced hypercatabolism through ghrelin/GHS-R1 alpha-POMC

Sustained hypercatabolism induced by sepsis contributed to serious complications and mortality in the intensive care unit. Enteral nutrition (EN) was required to maintain the energy balance during sepsis. Ghrelin, which was stimulated secretion by EN, had been shown to regulate energy homeostasis. Therefore, we tested whether EN alleviated hypercatabolism through ghrelin/GH secretagogue receptor 1 alpha (GHS-R1 alpha)-proopiomelanocortin (POMC) in endotoxemic rats. Rats in the Sham and lipopolysac-charide (LPS) groups were free access to rodent chow diet and water. Rats in the EN, EN + Lys and EN + 3-MA groups were intracerebroventricularly injected with saline, D-Lys(3)-GHRP-6 or 3-MA and then received EN for three days. Hypercatabolism was measured by the change of body weight, insulin resistance, leptin, corticosterone, muscle protein synthesis and atrophy. Serum and hypothalamic total ghrelin, acylated ghrelin, GHS-R1 alpha and AMP-activated protein kinase (AMPK)-autophagy-POMC pathway were also detected. The results showed that EN increased serum and hypothalamic total ghrelin, acylated ghrelin and GHS-R1 alpha, effectively activated the hypothalamic AMPK-autophagy-POMC pathway and alleviated hypercatabolism in endotoxemic rats. The improving effects of EN on hypercatabolism and hypothalamic AMPK-autophagy-POMC pathway were abolished with the central administration of D-Lys3-GHRP-6 to inhibited hypothalamic GHS-R1(.) And with the central administration of 3-MA to inhibited hypothalamic autophagy, the improving effect of EN on hypercatabolism was also abolished in endotoxemic rats. In conclusions, EN could significantly alleviate hypercatabolism through ghrelin/GHS-R1(-)POMC in endotoxemic rats. (c) 2022 Elsevier Inc. All rights reserved.