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Selective mtor inhibition via flcn drives tfe3-dependent vldl-tg secretion and protects from mafld/mash Chelsea Lauren Thorsheim
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Thorsheim, Chelsea Lauren, author.
- Language:
- English
- Subjects (All):
- Cellular biology.
- Molecular biology.
- Biology.
- Biochemistry.
- 0379.
- 0307.
- 0487.
- 0306.
- Local Subjects:
- Cellular biology.
- Molecular biology.
- Biology.
- Biochemistry.
- 0379.
- 0307.
- 0487.
- 0306.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (155 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Hepatic lipid homeostasis is controlled by multiple processes, including VLDL-TG secretion. We have previously shown that the FLCN/TFE3 branch of mTORC1 signaling controls hepatic fatty acid oxidation and de novo lipogenesis to protect mice from metabolic dysfunction-associated fatty liver disease (MAFLD). We now show that the FLCN/TFE3 pathway also controls VLDL-TG secretion via direct transcriptional activation of a broad program of genes involved in VLDL-TG secretion, including PCYT1A, the rate-limiting step of phosphatidylcholine synthesis. Loss of hepatic FLCN upregulates VLDL-TG secretion and prevents MAFLD, and this protection requires TFE3 and PCYT1A. The data unveil a new pathway that orchestrates multiple steps of VLDL-TG synthesis and secretion. The data also highlight that suppressing the selective FLCN/TFE3 branch of mTORC1 signaling maximizes hepatic lipid clearance by coordinately promoting fatty acid oxidation, suppressing de novo lipogenesis, and boosting VLDL-TG secretion, providing an attractive therapeutic target for the treatment of MAFLD
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Arany, Zoltan Committee members: Simon, Celeste; Abrams, Charles; Rader, Daniel; Titchenell, Paul
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247972815
- Access Restriction:
- Restricted for use by site license
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