GKRP-dependent modulation of feeding behavior by tanycyte-released monocarboxylates

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dc.coverageDOI: 10.7150/thno.66634
dc.creatorSalgado, Magdiel
dc.creatorElizondo-Vega, Roberto
dc.creatorVillar, Pablo S.
dc.creatorKonar, Macarena
dc.creatorGallegos, Scarlet
dc.creatorTarifeño-Saldivia, Estefanía
dc.creatorLuz-Crawford, Patricia
dc.creatorAguayo, Luis G.
dc.creatorAraneda, Ricardo C.
dc.creatorUribe, Elena
dc.creatorGarcía-Robles, María Ángeles
dc.date2022
dc.date.accessioned2025-11-18T19:41:45Z
dc.date.available2025-11-18T19:41:45Z
dc.description<p>Objectives: Glucokinase Regulatory Protein (GKRP) is the only known endogenous modulator of glucokinase (GK) localization and activity to date, and both proteins are localized in tanycytes, radial glia-like cells involved in metabolic and endocrine functions in the hypothalamus. However, the role of tanycytic GKRP and its impact on the regulation of feeding behavior has not been investigated. Here, we hypothesize that GKRP regulates feeding behavior by modulating tanycyte-neuron metabolic communication in the arcuate nucleus. Methods: We used primary cultures of tanycytes to evaluate the production of lactate and β-hydroxybutyrate (βHB). Similarly, we examined the electrophysiological responses to these metabolites in pro-opiomelanocortin (POMC) neurons in hypothalamic slices. To evaluate the role of GKRP in feeding behavior, we generated tanycyte-selective GKRP-overexpressing and GKRP-knock down mice (GKRPt-OE and GKRPt-KD respectively) using adenovirus-mediated transduction. Results: We demonstrated that lactate release induced by glucose uptake is favored in GKRP-KD tanycytes. Conversely, tanycytes overexpressing GKRP showed an increase in βHB efflux induced by low glucose concentration. In line with these findings, the excitability of POMC neurons was enhanced by lactate and decreased in the presence of βHB. In GKRPt-OE rats, we found an increase in post-fasting food avidity, whereas GKRPt-KD caused a significant decrease in feeding and body weight, which is reverted when MCT1 is silenced. Conclusion: Our study highlights the role of tanycytic GKRP in metabolic regulation and positions this regulator of GK as a therapeutic target for boosting satiety in patients with obesity problems.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/2802fbbe-c48f-44b1-abf1-8ea1e0f12221
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/51988
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.12 (2022) nr.4 p.1518-1536
dc.subjectFeeding behavior
dc.subjectGKRP
dc.subjectLactate
dc.subjectObesity
dc.subjectTanycyte
dc.subjectβ-hydroxybutyrate
dc.subjectSDG 3 - Good Health and Well-being
dc.titleGKRP-dependent modulation of feeding behavior by tanycyte-released monocarboxylateseng
dc.typeArticleeng
dc.typeArtículospa
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