Nutritional Modulation of Melatonin-SIRT1 Signaling by Octanoic Acid-Rich Enteral Nutrition Protects Against...

Area of Science:

• Gastroenterology
• Oncology
• Radiotherapy
• Nutrition Science

Background:

• Radiation-induced intestinal injury (RIII) is a severe complication of abdominopelvic radiotherapy, limiting treatment efficacy and patient quality of life.
• Standard enteral nutrition (EN) offers limited therapeutic benefits for RIII, necessitating novel nutritional interventions.

Purpose of the Study:

• To investigate the protective effects of octanoic acid (OA)-rich EN against RIII in a mouse model.
• To elucidate the underlying mechanisms, particularly the role of the melatonin-silent information regulator 1 (SIRT1) pathway.

Main Methods:

• C3H/HeN mice were subjected to radiation and treated with standard EN or OA-rich EN.
• Further experiments involved co-administration of OA-rich EN with melatonin or SIRT1 pathway inhibitors (Luzindole, EX527).
• Intestinal histopathology, apoptosis, tight junction protein expression, permeability, melatonin, inflammatory cytokines, and the SIRT1/PGC-1α/PPARγ pathway were assessed.

Main Results:

• OA-rich EN significantly improved intestinal histopathology, reduced apoptosis, and enhanced tight junction protein expression compared to standard EN.
• OA-rich EN promoted melatonin secretion and activated the SIRT1/PGC-1α/PPARγ pathway, leading to reduced inflammation.
• The protective effects of OA-rich EN were abolished by melatonin antagonists or SIRT1 inhibitors, confirming the pathway's involvement.

Conclusions:

• OA-rich EN alleviates RIII by promoting intestinal melatonin secretion, which subsequently activates the SIRT1/PGC-1α/PPARγ pathway.
• This study establishes OA-rich EN as a promising nutritional strategy to mitigate RIII and improve outcomes for patients undergoing abdominal radiotherapy.