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dc.contributor.advisorSingh, Rajat
dc.contributor.authorBatista-Gonzalez, Ana
dc.date.accessioned2020-04-01T09:31:23Z
dc.date.available2020-04-01T09:31:23Z
dc.date.issued2018
dc.identifier.citationSource: Dissertations Abstracts International, Volume: 80-05, Section: B.;Publisher info.: Dissertation/Thesis.;Advisors: Singh, Rajat.en_US
dc.identifier.isbn978-0-438-64065-8
dc.identifier.urihttps://yulib002.mc.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:11010200en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12202/5327
dc.description.abstractMechanistic target of rapamycin (mTOR) senses amino acids; however, its role in lipid metabolism is less established. Organismal lipid requirements are largely met through dietary intake. How nutrient sensing mechanisms in gut interface with dietary fat remains unclear. Here we reveal fundamental and cooperative roles for mTOR complexes 1 and 2 (mTORC1/2) in absorption of dietary triglycerides. Dietary lipid activates mTORC1/2 signaling in gut. Hyperactivating mTORC1 by deleting Tsc1 is sufficient to promote triglyceride absorption and metabolic disease in high fat-fed mice. Conversely, blocking mTORC1/2 by deleting Raptor or Rictor each decreases triglyceride absorption. Loss of Raptor sequesters lipid in Golgi in enterocytes and suppresses triglyceride secretion, while RictorKO mice show reduced triglycerides in enterocytes and circulation. Lipidomics in Rictor-null enterocytes revealed accumulation of diacylglycerols and funneling of absorbed fatty acids into phospholipids supporting triglyceride synthesis failure. Targeting mTOR signaling in gut may help counter hypertriglyceridemia and prevent cardiometabolic diseases. One Sentence Summary: Lipid activates mTORC1 and mTORC2, which play fundamental and cooperative roles in the absorption of dietary triglycerides.en_US
dc.language.isoen_USen_US
dc.publisherProQuest Dissertations & Theses Globalen_US
dc.subjectEndocrinologyen_US
dc.titlemTOR Impacts Metabolic Health by Regulating Dietary Lipid Absorptionen_US
dc.typeDissertationen_US
dc.typeThesisen_US


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