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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 -
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Department of New Biology Aging, Metabolism and Physiology Lab 1. Journal Articles

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