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dc.contributor.authorWang, Lifeng
dc.contributor.authorSinnott-Armstrong, Nicholas A
dc.contributor.authorWagschal, Alexandre
dc.contributor.authorWark, Abigail R.
dc.contributor.authorCamporez, Joao-Paulo
dc.contributor.authorPerry, Rachel J.
dc.contributor.authorJi, Fei
dc.contributor.authorSohn, Yoojin
dc.contributor.authorOh, Justin
dc.contributor.authorWu, Su
dc.contributor.authorChery, Jessica
dc.contributor.authorMoud, Bahareh Nemati
dc.contributor.authorSaadat, Alham
dc.contributor.authorDankel, Simon N
dc.contributor.authorMellgren, Gunnar
dc.contributor.authorTallapragada, Divya Sri Priyanka
dc.contributor.authorStrobel, Sophie Madlen
dc.contributor.authorLee, Mi-Jeong
dc.contributor.authorTewhey, Ryan
dc.contributor.authorSabeti, Pardis C.
dc.contributor.authorSchaefer, Anne
dc.contributor.authorPetri, Andreas
dc.contributor.authorKauppinen, Sakari
dc.contributor.authorChung, Raymond T.
dc.contributor.authorSoukas, Alexander
dc.contributor.authorAvruch, Joseph
dc.contributor.authorFried, Susan K.
dc.contributor.authorHauner, Hans
dc.contributor.authorSadreyev, Ruslan I.
dc.contributor.authorShulman, Gerald I.
dc.contributor.authorClaussnitzer, Melina
dc.contributor.authorNäär, Anders M.
dc.date.accessioned2021-06-28T09:30:59Z
dc.date.available2021-06-28T09:30:59Z
dc.date.created2020-11-08T13:13:46Z
dc.date.issued2020
dc.PublishedCell. 2020, 183 (3), 684-701.
dc.identifier.issn0092-8674
dc.identifier.urihttps://hdl.handle.net/11250/2761549
dc.description.abstractPositive selection in Europeans at the 2q21.3 locus harboring the lactase gene has been attributed to selection for the ability of adults to digest milk to survive famine in ancient times. However, the 2q21.3 locus is also associated with obesity and type 2 diabetes in humans, raising the possibility that additional genetic elements in the locus may have contributed to evolutionary adaptation to famine by promoting energy storage, but which now confer susceptibility to metabolic diseases. We show here that the miR-128-1 microRNA, located at the center of the positively selected locus, represents a crucial metabolic regulator in mammals. Antisense targeting and genetic ablation of miR-128-1 in mouse metabolic disease models result in increased energy expenditure and amelioration of high-fat-diet-induced obesity and markedly improved glucose tolerance. A thrifty phenotype connected to miR-128-1-dependent energy storage may link ancient adaptation to famine and modern metabolic maladaptation associated with nutritional overabundance.en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.titleA MicroRNA Linking Human Positive Selection and Metabolic Disordersen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionacceptedVersionen_US
dc.rights.holderCopyright 2020 Elsevieren_US
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode2
dc.identifier.doi10.1016/j.cell.2020.09.017
dc.identifier.cristin1845910
dc.source.journalCellen_US
dc.source.40183
dc.source.143
dc.source.pagenumber684-701en_US
dc.identifier.citationCell. 2020, 183 (3), 684-701en_US
dc.source.volume183en_US
dc.source.issue3en_US


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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal