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Nischarin inhibition alters energy metabolism by activating AMP-activated protein kinase

dc.contributor.authorDong, Shengli
dc.contributor.authorBaranwal, Somesh
dc.contributor.authorGarcia, Anapatricia
dc.contributor.authorSerrano-Gomez, Silvia
dc.contributor.authorEastlack, Steven
dc.contributor.authorIwakuma, Tomoo
dc.contributor.authorMercante, Donald
dc.contributor.authorMauvais-Jarvis, Franck
dc.contributor.authorAlahari, Suresh K.
dc.contributor.authorDong, S.
dc.contributor.authorBaranwal, S.
dc.contributor.authorGarcia, A.
dc.contributor.authorSerrano-Gomez, S.J.
dc.contributor.authorEastlack, S.
dc.contributor.authorIwakuma, T.
dc.contributor.authorMercante, D.
dc.contributor.authorMauvais-Jarvis, F.
dc.contributor.authorAlahari, S.K.
dc.date.accessioned2018-02-08T13:00:59Z
dc.date.available2018-02-08T13:00:59Z
dc.date.issued2017
dc.identifier.citationDong, S., Baranwal, S., Garcia, A., Serrano-Gomez, S. J., Eastlack, S., Iwakuma, T., . . . Alahari, S. K. (2017). Nischarin inhibition alters energy metabolism by activating AMP-activated protein kinase. Journal of Biological Chemistry, 292(41), 16833-16846. doi: 10.1074/jbc.M117.784256en_US
dc.identifier.issn219258
dc.identifier.urihttp://kr.cup.edu.in/handle/32116/595
dc.description.abstractNischarin (Nisch) is a key protein functioning as a molecular scaffold and thereby hosting interactions with several protein partners. To explore the physiological importance of Nisch, here we generated Nisch loss-of-function mutant mice and analyzed their metabolic phenotype. Nisch-mutant embryos exhibited delayed development, characterized by small size and attenuated weight gain. We uncovered the reason for this phenotype by showing that Nisch binds to and inhibits the activity of AMP-activated protein kinase (AMPK), which regulates energy homeostasis by suppressing anabolic and activating catabolic processes. The Nisch mutations enhanced AMPK activation and inhibited mechanistic target of rapamycin signaling in mouse embryonic fibroblasts as well as in muscle and liver tissues of mutant mice. Nisch-mutant mice also exhibited increased rates of glucose oxidation with increased energy expenditure, despite reduced overall food intake. Moreover, the Nisch-mutant mice had reduced expression of liver markers of gluconeogenesis associated with increased glucose tolerance. As a result, these mice displayed decreased growth and body weight. Taken together, our results indicate that Nisch is an important AMPK inhibitor and a critical regulator of energy homeostasis, including lipid and glucose metabolism. ? 2017 by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc.en_US
dc.subjectCell cultureen_US
dc.subjectChemical activationen_US
dc.subjectEnzyme activityen_US
dc.subjectEnzymesen_US
dc.subjectGlucoseen_US
dc.subjectMammalsen_US
dc.subjectMedical problemsen_US
dc.subjectPhysiologyen_US
dc.subjectProteinsen_US
dc.subjectScaffolds (biology)en_US
dc.subjectAMP-activated protein kinaseen_US
dc.subjectEnergy homeostasisen_US
dc.subjectGlucose metabolismen_US
dc.subjectLoss-of-function mutantsen_US
dc.subjectMetabolic phenotypeen_US
dc.subjectMolecular scaffoldsen_US
dc.subjectMouse embryonic fibroblastsen_US
dc.subjectTarget of rapamycinen_US
dc.subjectMetabolismen_US
dc.subjectNischarinen_US
dc.subjectScaffold proteinen_US
dc.subjectUnclassified drugen_US
dc.subjectGlucoseen_US
dc.titleNischarin inhibition alters energy metabolism by activating AMP-activated protein kinaseen_US
dc.typeArticleen_US
dc.identifier.doi10.1074/jbc.M117.784256
dc.identifier.urlhttp://www.jbc.org/content/292/41/16833
dc.title.journalJournal of Biological Chemistry


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