Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Lee, Jae Min | - |
dc.contributor.author | Salazar Hernández, Mario Andrés | - |
dc.contributor.author | Auen, Thomas | - |
dc.contributor.author | Mucka, Patrick | - |
dc.contributor.author | Lee, Justin | - |
dc.contributor.author | Ozcan, Umut | - |
dc.date.available | 2018-02-05T04:11:34Z | - |
dc.date.created | 2018-01-18 | - |
dc.date.issued | 2018-01 | - |
dc.identifier.issn | 2212-8778 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/5603 | - |
dc.description.abstract | Objective Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) promotes hepatic gluconeogenesis by activating HNF4α and FoxO1. PGC-1α expression in the liver is highly elevated in obese and diabetic conditions, leading to increased hepatic glucose production. We previously showed that the spliced form of X-box binding protein 1 (XBP1s) suppresses FoxO1 activity and hepatic gluconeogenesis. The shared role of PGC-1α and XBP1s in regulating FoxO1 activity and gluconeogenesis led us to investigate the probable interaction between PGC-1α and XBP1s and its role in glucose metabolism. Methods We investigated the biochemical interaction between PGC-1α and XBP1s and examined the role of their interaction in glucose homeostasis using animal models. Results We show that PGC-1α interacts with XBP1s, which plays an anti-gluconeogenic role in the liver by suppressing FoxO1 activity. The physical interaction between PGC-1α and XBP1s leads to suppression of XBP1s activity rather than its activation. Upregulating PGC-1α expression in the liver of lean mice lessens XBP1s protein levels, and reducing PGC-1α levels in obese and diabetic mouse liver restores XBP1s protein induction. Conclusions Our findings reveal a novel function of PGC-1α as a suppressor of XBP1s function, suggesting that hepatic PGC-1α promotes gluconeogenesis through multiple pathways as a co-activator for HNF4α and FoxO1 and also as a suppressor for anti-gluconeogenic transcription factor XBP1s. © 2017 The Authors | - |
dc.language | English | - |
dc.publisher | Elsevier GmbH | - |
dc.title | PGC-1 alpha functions as a co-suppressor of XBP1 s to regulate glucose metabolism | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.molmet.2017.10.010 | - |
dc.identifier.scopusid | 2-s2.0-85033493250 | - |
dc.identifier.bibliographicCitation | Molecular Metabolism, v.7, pp.119 - 131 | - |
dc.description.isOpenAccess | TRUE | - |
dc.subject.keywordAuthor | PGC-1 alpha | - |
dc.subject.keywordAuthor | XBP1s | - |
dc.subject.keywordAuthor | Glucose homeostasis | - |
dc.subject.keywordAuthor | ER stress | - |
dc.subject.keywordAuthor | UPR | - |
dc.subject.keywordAuthor | Insulin resistance | - |
dc.subject.keywordPlus | ENDOPLASMIC-RETICULUM STRESS | - |
dc.subject.keywordPlus | UNFOLDED PROTEIN RESPONSE | - |
dc.subject.keywordPlus | TRANSCRIPTIONAL COACTIVATOR PGC-1 | - |
dc.subject.keywordPlus | HEPATIC GLUCONEOGENESIS | - |
dc.subject.keywordPlus | ER STRESS | - |
dc.subject.keywordPlus | ENERGY-METABOLISM | - |
dc.subject.keywordPlus | RECEPTOR-ALPHA | - |
dc.subject.keywordPlus | ADIPOSE-TISSUE | - |
dc.subject.keywordPlus | MESSENGER-RNA | - |
dc.subject.keywordPlus | UNITED-STATES | - |
dc.citation.endPage | 131 | - |
dc.citation.startPage | 119 | - |
dc.citation.title | Molecular Metabolism | - |
dc.citation.volume | 7 | - |