Altered purine and pentose phosphate pathway metabolism in uteroplacental insufficiency-induced intrauterine growth restriction offspring rats impair intestinal function.

Ho, Sheng-Yuan; Yuliana, Merryl Esther; Chou, Hsiu-Chu; Huang, Liang-Ti; Chen, Chung-Ming

Ho, Sheng-Yuan; Yuliana, Merryl Esther; Chou, Hsiu-Chu; Huang, Liang-Ti; Chen, Chung-Ming.

Afiliación

Ho SY; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Yuliana ME; International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Faculty of Medicine, Christian University of Indonesia, Jakarta, Indonesia.
Chou HC; Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Huang LT; Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chen CM; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical Universi

J Nutr Biochem ; 134: 109737, 2024 Aug 13.

Article en En | MEDLINE | ID: mdl-39147244

ABSTRACT

ABSTRACT

This study aimed to identify metabolic alterations in the small intestine of newborn rats with intrauterine growth restriction (IUGR), a condition linked to intestinal dysfunction. Pregnant Sprague Dawley rats underwent bilateral uterine artery ligation on gestational day 17 to induce intrauterine growth restriction or sham surgery. Rat pups were delivered spontaneously on gestational day 22. Small intestine tissues were collected on postnatal days 0 and 7 from offspring. Liquid chromatography-mass spectrometry analysis was performed to investigate untargeted metabolomic profiles. Western blot analysis assessed protein expression of key regulators. Newborn rats with intrauterine growth restriction exhibited distinct small intestine metabolic profiles compared to controls on postnatal day 0. Notably, significant alterations were observed in purine metabolism, the pentose phosphate pathway, and related pathways. Western blot analysis revealed a decrease expression in transketolase, a key enzyme of the pentose phosphate pathway, suggesting impaired activity of the pentose phosphate pathway. Additionally, decreased expression of tight junction proteins ZO-1 and occludin indicated compromised intestinal barrier function in rats with intrauterine growth restriction. Similar metabolic disruptions persisted on postnatal day 7, with further reductions in tricarboxylic acid cycle intermediates and folate biosynthesis precursors. Interestingly, lysyl-glycine, a protein synthesis marker, was elevated in rats with intrauterine growth restriction. Our findings reveal a distinct metabolic signature in the small intestine of neonatal rats with intrauterine growth restriction, characterized by disruptions in the pentose phosphate pathway, purine metabolism, and energy production pathways. These novel insights suggest potential mechanisms underlying IUGR-associated intestinal dysfunction and impaired growth.

Palabras clave

Intestinal dysfunction; Intrauterine growth restriction; Metabolomics; Pentose phosphate pathway; Purine metabolism; Uteroplacental insufficiency

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Nutr Biochem Asunto de la revista: BIOQUIMICA / CIENCIAS DA NUTRICAO Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos

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