Enteral Nutrition Fights Muscle Wasting by Boosting Ghrelin Pathway

In critical illness or conditions like sepsis, the body can enter a state of hypercatabolism, where tissues, especially muscle, are rapidly broken down. This process is often triggered by inflammatory mediators such as lipopolysaccharides (LPS), leading to significant weight loss and poor outcomes. While enteral nutrition (feeding through the gastrointestinal tract) is a standard supportive therapy, the precise molecular mechanisms by which it counteracts LPS-induced hypercatabolism, particularly involving the ghrelin/GHS-R1α-POMC pathway, have remained underexplored.

The study revealed that LPS administration significantly induced hypercatabolism, evidenced by a 15-20% reduction in body weight and a 30-40% increase in muscle protein degradation markers (e.g., MuRF1, Atrogin-1) compared to controls (p<0.01). Furthermore, LPS suppressed circulating ghrelin levels by 35% and reduced hypothalamic GHS-R1α expression by 25% (p<0.05). Enteral nutrition markedly attenuated these catabolic effects, reducing LPS-induced weight loss by 50% (to only 7-10% reduction) and decreasing muscle protein degradation markers by 45-55% (p<0.001) compared to the LPS-alone group. Mechanistically, enteral nutrition significantly increased circulating ghrelin levels by 2.3-fold (p<0.01) and enhanced the expression of its receptor, GHS-R1α, in the hypothalamus by 1.8-fold (p<0.05) in LPS-treated animals. Moreover, EN restored POMC (pro-opiomelanocortin) expression, which was suppressed by LPS, to near control levels (p<0.01), suggesting a crucial role for this pathway. The researchers also demonstrated that pharmacological blockade of the ghrelin receptor significantly abrogated the beneficial effects of EN, confirming the pathway's involvement.