Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures

• DOI: 10.1007/s00204-024-03773-8
• Publication Date: 2024-05-14T04:12:42Z
• Authors: Milos Mihajlovic; Sybren De Boever; Andrés Tabernilla; Ellen Callewaert; Julen Sanz-Serrano; Anouk Verhoeven; Amy Maerten; Zenzi Rosseel; Elisabeth De Waele; Mathieu Vinken
• Keywords: Steatosis; Liver disease; Enteral administration

Abstract Parenteral nutrition (PN) is typically administered to individuals with gastrointestinal dysfunction, a contraindication for enteral feeding, and need nutritional therapy. When PN the only energy source in patients, it defined as total parenteral (TPN). TPN life-saving approach different patient populations, both infants adults. However, despite numerous benefits, can cause adverse effects, including metabolic disorders liver injury. TPN-associated injury, known intestinal failure-associated disease (IFALD), represents significant problem affecting up 90% of receiving TPN. IFALD pathogenesis complex, depending on components well patient’s medical conditions. Despite animal studies clinical observations, molecular mechanisms driving remain largely unknown. The present study was set elucidate underlying IFALD. For this purpose, human spheroid co-cultures were treated mixture, followed by RNA sequencing analysis. Subsequently, following exposure its single components, several key events mitochondrial endoplasmic reticulum stress, oxidative apoptosis, lipid accumulation (steatosis), studied using various techniques. It found that prolonged substantially changes transcriptome profile spheroids affects multiple signaling pathways contributing Moreover, main especially emulsion, induce all measured trigger steatosis.