Ablation of glucokinase-expressing tanycytes impacts energy balance and increases adiposity in mice

• DOI: 10.1016/j.molmet.2021.101311
• Publication Date: 2021-07-26T05:38:25Z
• Authors: Antoine Rohrbach; Emilie Caron; Rafik Dali; Maxime Brunner; Roxane Pasquettaz; Irina Kolotuev; Federico Santoni; Bernard Thorens; Fanny Langlet
• Keywords: Male; 0303 health sciences; [SDV]Life Sciences [q-bio]; Tanycytes; Ependymoglial Cells; Hypothalamus; Apoptosis; Mice, Transgenic; Energy balance; Glucose homeostasis; RC31-1245; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Glucokinase; Animals; Original Article; Energy Metabolism; Internal medicine; Adiposity

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.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.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.This study describes the role of GCK in tanycyte biology and highlights the impact of tanycyte loss on the regulation of energy balance.