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dc.contributor.authorLiu, Sihaoen_US
dc.contributor.authorBrown, Jonathan D.en_US
dc.contributor.authorStanya, Kristopher J.en_US
dc.contributor.authorHoman, Edwinen_US
dc.contributor.authorLeidl, Mathiasen_US
dc.contributor.authorInouye, Karenen_US
dc.contributor.authorBhargava, Prernaen_US
dc.contributor.authorGangl, Matthew R.en_US
dc.contributor.authorDai, Linglingen_US
dc.contributor.authorHatano, Benen_US
dc.contributor.authorHotamisligil, Gökhan S.en_US
dc.contributor.authorSaghatelian, Alanen_US
dc.contributor.authorPlutzky, Jorgeen_US
dc.contributor.authorLee, Chih-Haoen_US
dc.date.accessioned2014-09-08T15:36:21Z
dc.date.issued2014en_US
dc.identifier.citationLiu, S., J. D. Brown, K. J. Stanya, E. Homan, M. Leidl, K. Inouye, P. Bhargava, et al. 2014. “A diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid utilization.” Nature 502 (7472): 550-554. doi:10.1038/nature12710. http://dx.doi.org/10.1038/nature12710.en
dc.identifier.issn0028-0836en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12785841
dc.description.abstractFood intake increases the activity of hepatic de novo lipogenesis, which mediates the conversion of glucose to fats for storage or utilization. In mice, this program follows a circadian rhythm that peaks with nocturnal feeding1,2 and is repressed by Rev-erbα/β and an HDAC3-containing complex3–5 during the day. The transcriptional activators controlling rhythmic lipid synthesis in the dark cycle remain poorly defined. Disturbances in hepatic lipogenesis are also associated with systemic metabolic phenotypes6–8, suggesting that lipogenesis in the liver communicates with peripheral tissues to control energy substrate homeostasis. Here we identify a PPARδ-dependent de novo lipogenic pathway in the liver that modulates fat utilization by muscle via a circulating lipid. The nuclear receptor PPARδ controls diurnal expression of lipogenic genes in the dark/feeding cycle. Liver-specific PPARδ activation increases, while hepatocyte-Ppard deletion reduces, muscle fatty acid (FA) uptake. Unbiased metabolite profiling identifies PC(18:0/18:1), or 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), as a serum lipid regulated by diurnal hepatic PPARδ activity. PC(18:0/18:1) reduces postprandial lipid levels and increases FA utilization through muscle PPARα. High fat feeding diminishes rhythmic production of PC(18:0/18:1), whereas PC(18:0/18:1) administration in db/db mice improves metabolic homeostasis. These findings reveal an integrated regulatory circuit coupling lipid synthesis in the liver to energy utilization in muscle by coordinating the activity of two closely related nuclear receptors. These data implicate alterations in diurnal hepatic PPARδ-PC(18:0/18:1) signaling in metabolic disorders including obesity.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/nature12710en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141623/pdf/en
dash.licenseLAAen_US
dc.titleA diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid utilizationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNatureen
dash.depositing.authorBrown, Jonathan D.en_US
dc.date.available2014-09-08T15:36:21Z
dc.identifier.doi10.1038/nature12710*
dash.authorsorderedfalse
dash.contributor.affiliatedLeidl, Mathias
dash.contributor.affiliatedGangl, Matthew
dash.contributor.affiliatedBrown, Jonathan D.
dash.contributor.affiliatedPlutzky, Jorge
dash.contributor.affiliatedLee, Chih-Hao
dash.contributor.affiliatedInouye, Karen
dash.contributor.affiliatedHotamisligil, Gokhan


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