Ablation of glucokinase-expressing tanycytes impacts energy balance and increases adiposity in mice
| العنوان: | Ablation of glucokinase-expressing tanycytes impacts energy balance and increases adiposity in mice |
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| المؤلفون: | Fanny Langlet, Bernard Thorens, Antoine Rohrbach, Irina Kolotuev, Emilie Caron, Roxane Pasquettaz, Federico Santoni, Rafik Dali, Maxime Brunner |
| المصدر: | Molecular Metabolism Molecular Metabolism, Vol 53, Iss, Pp 101311-(2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Apoptosis, Glucose homeostasis, ARH, arcuate nucleus, Mice, DIO2, deiodinase 2, 0302 clinical medicine, CART, cocaine- and amphetamine-related transcript, Glucokinase, Internal medicine, Adiposity, 0303 health sciences, AgRP, agouti-related peptide, Tanycyte, Tanycytes, GCK, glucokinase, medicine.anatomical_structure, Hypothalamus, vmARH, ventromedial arcuate nucleus, Original Article, medicine.medical_specialty, Ependymoglial Cells, NPY, neuropeptide Y, Cre recombinase, Mice, Transgenic, DMH, dorsomedial nucleus, In situ hybridization, Energy balance, Biology, 03 medical and health sciences, POMC, proopiomelanocortin, 2-DG, 2-deoxyglucose, Arcuate nucleus, medicine, Animals, ME, median eminence, Molecular Biology, VMH, ventromedial nucleus, 030304 developmental biology, Cell Biology, RC31-1245, Mice, Inbred C57BL, Endocrinology, Neuron, Energy Metabolism, 030217 neurology & neurosurgery |
| الوصف: | Objectives Glucokinase (GCK) is critical for glucosensing. In rats, GCK is expressed in hypothalamic tanycytes and appears to play an essential role in feeding behavior. In this study, we investigated the distribution of GCK-expressing tanycytes in mice and their role in the regulation of energy balance. Methods In situ hybridization, reporter gene assay, and immunohistochemistry were used to assess GCK expression along the third ventricle in mice. To evaluate the impact of GCK-expressing tanycytes on arcuate neuron function and mouse physiology, Gck deletion along the ventricle was achieved using loxP/Cre recombinase technology in adult mice. Results GCK expression was low along the third ventricle, but detectable in tanycytes facing the ventromedial arcuate nucleus from bregma −1.5 to −2.2. Gck deletion induced the death of this tanycyte subgroup through the activation of the BAD signaling pathway. The ablation of GCK-expressing tanycytes affected different aspects of energy balance, leading to an increase in adiposity in mice. This phenotype was systematically associated with a defect in NPY neuron function. In contrast, the regulation of glucose homeostasis was mostly preserved, except for glucoprivic responses. Conclusions This study describes the role of GCK in tanycyte biology and highlights the impact of tanycyte loss on the regulation of energy balance. Graphical abstract Image 1 Highlights • vmARH tanycytes express glucokinase. • Glucokinase deletion in tanycytes induces cell death. • Ablation of vmARH tanycytes alters energy balance and adiposity. • Ablation of vmARH tanycytes alters NPY neuron function. |
| تدمد: | 2212-8778 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::04c27ff32b82421b71e5764fb0b90600 https://pubmed.ncbi.nlm.nih.gov/34325016 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....04c27ff32b82421b71e5764fb0b90600 |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 22128778 |
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