ArticleMolecular metabolism2016
Mediobasal hypothalamic overexpression of DEPTOR protects against high-fat diet-induced obesity.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus.Molecular diversity · 2026Article
- Recent Updates on the Role of Genetic and Epigenetic Factors in the Pathogenesis of the Metabolic Syndrome.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Article
- Changes of Signaling Pathways in Hypothalamic Neurons with Aging.Current issues in molecular biology · 2023Review
- Mechanistic Target of Rapamycin Complex 1: From a Nutrient Sensor to a Key Regulator of Metabolism and Health.Advances in nutrition (Bethesda, Md.) · 2022Article
- Regulation of human mTOR complexes by DEPTOR.eLife · 2021Article
- Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace.eLife · 2021Article
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Pharmacological chaperone action in humanized mouse models of MC4R-linked obesity.JCI insight · 2021Article
- miRNA-182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury.Journal of cellular and molecular medicine · 2020Article
- Modulation of hypothalamic S6K1 and S6K2 alters feeding behavior and systemic glucose metabolism.The Journal of endocrinology · 2020Article
- The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis.Molecular metabolism · 2019Article
- Molecular Mechanisms of Hypothalamic Insulin Resistance.International journal of molecular sciences · 2019Review
- mTOR as a central regulator of lifespan and aging.F1000Research · 2019Review
- Role of mTOR in Glucose and Lipid Metabolism.International journal of molecular sciences · 2018Review
- DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.Physiological reviews · 2018Review
- Loss of DEPTOR in renal tubules protects against cisplatin-induced acute kidney injury.Cell death & disease · 2018Article
- Dynamic modelling of the mTOR signalling network reveals complex emergent behaviours conferred by DEPTOR.Scientific reports · 2018Article
- TOR-mediated regulation of metabolism in aging.Aging cell · 2017Review
- FTO associations with obesity and telomere length.Journal of biomedical science · 2017Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
objectiveThe mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulate energy homeostasis. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to dampen mTORC1 function, consequently reducing mTORC1 negative feedbacks and promoting insulin signaling and Akt/PKB activation in several models. Recently, we observed that DEPTOR is expressed in several structures of the brain including the mediobasal hypothalamus (MBH), a region that regulates energy balance. Whether DEPTOR in the MBH plays a functional role in regulating energy balance and hypothalamic insulin signaling has never been tested.
methodsWe have generated a novel conditional transgenic mouse model based on the Cre-LoxP system allowing targeted overexpression of DEPTOR. Mice overexpressing DEPTOR in the MBH were subjected to a metabolic phenotyping and MBH insulin signaling was evaluated.
resultsWe first report that systemic (brain and periphery) overexpression of DEPTOR prevents high-fat diet-induced obesity, improves glucose metabolism and protects against hepatic steatosis. These phenotypes were associated with a reduction in food intake and feed efficiency and an elevation in oxygen consumption. Strikingly, specific overexpression of DEPTOR in the MBH completely recapitulated these phenotypes. DEPTOR overexpression was associated with an increase in hypothalamic insulin signaling, as illustrated by elevated Akt/PKB activation.
conclusionAltogether, these results support a role for MBH DEPTOR in the regulation of energy balance and metabolism.
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