ArticleMolecular metabolism2017
Loss of hepatic DEPTOR alters the metabolic transition to fasting.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Normalization of trophoblast mTOR signaling rescues impaired function in primary human trophoblast cells isolated from pregnancies complicated by fetal growth restriction.Cell death discovery · 2025Article
- Generation and characterization of a Cre-inducible ZNF768 overexpression mouse model.Scientific reports · 2025Article
- Trophoblast-specific Deptor knockdown enhances trophoblast nutrient transport and fetal growth in mice.Acta physiologica (Oxford, England) · 2025Article
- Hypolipidemic Effects of Beetroot Juice in SHR-CRP and HHTg Rat Models of Metabolic Syndrome: Analysis of Hepatic Proteome.Metabolites · 2023Article
- Crosstalk between Glycogen-Selective Autophagy, Autophagy and Apoptosis as a Road towards Modifier Gene Discovery and New Therapeutic Strategies for Glycogen Storage Diseases.Life (Basel, Switzerland) · 2022Review
- Formimidoyltransferase cyclodeaminase prevents the starvation-induced liver hepatomegaly and dysfunction through downregulating mTORC1.PLoS genetics · 2021Article
- Limited survival and impaired hepatic fasting metabolism in mice with constitutive Rag GTPase signaling.Nature communications · 2021Article
- Tanc2-mediated mTOR inhibition balances mTORC1/2 signaling in the developing mouse brain and human neurons.Nature communications · 2021Article
- Metabolic responses to intermittent hypoxia are regulated by sex and estradiol in mice.American journal of physiology. Endocrinology and metabolism · 2021Article
- DEPTOR stabilizes ErbB2 to promote the proliferation and survival of ErbB2-positive breast cancer cells.Theranostics · 2021Article
- Role of exercise and rapamycin on the expression of energy metabolism genes in liver tissues of rats fed a high‑fat diet.Molecular medicine reports · 2020Article
- miRNA-182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury.Journal of cellular and molecular medicine · 2020Article
- HIF-mediated Suppression of DEPTOR Confers Resistance to mTOR Kinase Inhibition in Renal Cancer.iScience · 2019Article
- RETRACTED: A Novel Therapeutic Induces DEPTOR Degradation in Multiple Myeloma Cells with Resulting Tumor Cytotoxicity.Molecular cancer therapeutics · 2019Article
- Novel roles of mechanistic target of rapamycin signaling in regulating fetal growth†.Biology of reproduction · 2019Review
- Fasting Physiology and Therapeutic Diets: A Look Back to the Future.Integrative medicine (Encinitas, Calif.) · 2019Article
- Concurrent activation of growth factor and nutrient arms of mTORC1 induces oxidative liver injury.Cell discovery · 2019Article
- Regulation of metabolic health by essential dietary amino acids.Mechanisms of ageing and development · 2019Review
- DEPTOR modulates activation responses in CD4American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.Physiological reviews · 2018Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveThe mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulates growth and metabolism. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to reduce their activity. Whether DEPTOR loss affects metabolism and organismal growth
methodsWe have generated a conditional transgenic mouse allowing the tissue-specific deletion of DEPTOR. This model was crossed with CMV-cre mice or Albumin-cre mice to generate either whole-body or liver-specific DEPTOR knockout (KO) mice.
resultsWhole-body DEPTOR KO mice are viable, fertile, normal in size, and do not display any gross physical and metabolic abnormalities. To circumvent possible compensatory mechanisms linked to the early and systemic loss of DEPTOR, we have deleted DEPTOR specifically in the liver, a tissue in which DEPTOR protein is expressed and affected in response to mTOR activation. Liver-specific DEPTOR null mice showed a reduction in circulating glucose upon fasting versus control mice. This effect was not associated with change in hepatic gluconeogenesis potential but was linked to a sustained reduction in circulating glucose during insulin tolerance tests. In addition to the reduction in glycemia, liver-specific DEPTOR KO mice had reduced hepatic glycogen content when fasted. We showed that loss of DEPTOR cell-autonomously increased oxidative metabolism in hepatocytes, an effect associated with increased cytochrome c expression but independent of changes in mitochondrial content or in the expression of genes controlling oxidative metabolism. We found that liver-specific DEPTOR KO mice showed sustained mTORC1 activation upon fasting, and that acute treatment with rapamycin was sufficient to normalize glycemia in these mice.
conclusionWe propose a model in which hepatic DEPTOR accelerates the inhibition of mTORC1 during the transition to fasting to adjust metabolism to the nutritional status.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.