ArticleMolecular neurobiology2020
Glial Endozepines Reverse High-Fat Diet-Induced Obesity by Enhancing Hypothalamic Response to Peripheral Leptin.
Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Written in the Stars: Astrocyte Biology From Evolution to Disease.Acta physiologica (Oxford, England) · 2026Review
- Tanycytes: bloodhounds of the metabolic brain.Trends in endocrinology and metabolism: TEM · 2026Review
- The role of tanycytes in the regulation of energy balance.Reviews in endocrine & metabolic disorders · 2026Review
- Metabolic regulation by tanycyte-derived extracellular vesicles through insulin precursor-mediated neuronal recognition and mTORC component delivery.Nature metabolism · 2026Article
- Therapeutic potential for glial-derived octadecaneuropeptide in the treatment of obesity.Expert opinion on therapeutic targets · 2026Article
- Insulin evokes release of endozepines from astrocytes of the NTS to modulate glucose metabolism in male rats.Molecular metabolism · 2025Article
- Sex differences in central endozepine expression and regulation of appetite.Physiology & behavior · 2025Article
- Hindbrain octadecaneuropeptide gliotransmission as a therapeutic target for energy balance control without nausea or emesis.Science translational medicine · 2025Article
- 3,5-Dimethyl-2,4,6-trimethoxychalcone Lessens Obesity and MAFLD in Leptin-DeficientInternational journal of molecular sciences · 2024Article
- Ovarian hormones and eating disorders.Frontiers in psychology · 2024Review
- Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies.International journal of molecular sciences · 2023Review
- Constitutively active microglial populations limit anorexia induced by the food contaminant deoxynivalenol.Journal of neuroinflammation · 2022Article
- Glial cells as integrators of peripheral and central signals in the regulation of energy homeostasis.Nature metabolism · 2022Review
- Glial Modulation of Energy Balance: The Dorsal Vagal Complex Is No Exception.International journal of molecular sciences · 2022Review
- From benzodiazepines to fatty acids and beyond: revisiting the role of ACBP/DBI.Trends in endocrinology and metabolism: TEM · 2021Review
- Astrocyte Gliotransmission in the Regulation of Systemic Metabolism.Metabolites · 2021Review
- Tanycytic networks mediate energy balance by feeding lactate to glucose-insensitive POMC neurons.The Journal of clinical investigation · 2021Article
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Research on energy homeostasis has focused on neuronal signaling; however, the role of glial cells has remained little explored. Glial endozepines exert anorexigenic actions by mechanisms which remain poorly understood. In this context, the present study was designed to decipher the mechanisms underlying the anorexigenic action of endozepines and to investigate their potential curative effect on high-fat diet-induced obesity. We carried out a combination of physiological, pharmacological, and molecular analyses together to dissect the underlying mechanisms of endozepine-induced hypophagia. To evaluate the potential anti-obesity effect of endozepines, different model of obesity were used, i.e., ob/ob and diet-induced obese mice. We show that the intracerebral administration of endozepines enhances satiety by targeting anorexigenic brain circuitry and induces STAT3 phosphorylation, a hallmark of leptin signaling. Strikingly, endozepines are entirely ineffective at reducing food intake in the presence of a circulating leptin antagonist and in leptin-deficient mice (ob/ob) but potentiate the reduced food intake and weight loss induced by exogenous leptin administration in these animals. Endozepines reversed high fat diet-induced obesity by reducing food intake and restored leptin-induced STAT3 phosphorylation in the hypothalamus. Interestingly, we observed that glucose and insulin synergistically enhance tanycytic endozepine expression and release. Finally, endozepines, which induce ERK activation necessary for leptin transport into the brain in cultured tanycytes, require tanycytic leptin receptor expression to promote STAT3 phosphorylation in the hypothalamus. Our data identify endozepines as potential anti-obesity compounds in part through the modulation of the LepR-ERK-dependent tanycytic leptin shuttle.
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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 Socratic graph.