title: XBP-1s is linked to suppressed gluconeogenesis in the Ebb phase of burn injury.
abstract: The first 24 h following burn injury is known as the ebb phase and is characterized by a depressed metabolic rate. While the postburn ebb phase has been well described, the molecular mechanisms underlying this response are poorly understood. The endoplasmic reticulum (ER) regulates metabolic rate by maintaining glucose homeostasis through the hepatic ER stress response. We have shown that burn injury leads to ER stress in the liver during the first 24 h following thermal injury. However, whether ER stress is linked to the metabolic responses during the ebb phase of burn injury is poorly understood. Here, we show in an animal model that burn induces activation of activating transcription factor 6 (ATF6) and inositol requiring enzyme-1 (IRE-1) and this leads to increased expression of spliced X-box binding protein-1 (XBP-1s) messenger ribonucleic acid (mRNA) during the ebb phase. This is associated with increased expression of XBP-1 target genes and downregulation of the key gluconeogenic enzyme glucose-6-phosphatase (G6Pase). We conclude that upregulation of the ER stress response after burn injury is linked to attenuated gluconeogenesis and sustained glucose tolerance in the postburn ebb phase.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Natasha C
authors.initials: NC
authors.lastname: Brooks
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Marshall
authors.forename: Nour
authors.initials: N
authors.lastname: Qa'aty
authors.forename: Yaeko
authors.initials: Y
authors.lastname: Hiyama
authors.forename: Darren
authors.initials: D
authors.lastname: Boehning
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002056:Burns / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005943:Gluconeogenesis / Q000235:genetics*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D000071717:X-Box Binding Protein 1; D000071161:Forkhead Box Protein O1
chemical_list: D001786:Blood Glucose; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D005952:Glucose-6-Phosphatase; D007328:Insulin; D009419:Nerve Tissue Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605545:Xbp1 protein, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1