Fasting induces metabolic switches and spatial redistributions of lipid processing and neuronal interactions in tanycytes.

The ependyma lining the third ventricle (3V) in the mediobasal hypothalamus plays a crucial role in energy balance and glucose homeostasis. It is characterized by a high functional heterogeneity and plasticity, but the underlying molecular mechanisms governing its features are not fully understood. Here, 5481 hypothalamic ependymocytes were cataloged using FACS-assisted scRNAseq from fed, 12h-fasted, and 24h-fasted adult male mice. With standard clustering analysis, typical ependymal cells and ß2-tanycytes appear sharply defined, but other subpopulations, ß1- and α-tanycytes, display fuzzy boundaries with few or no specific markers. Pseudospatial approaches, based on the 3V neuroanatomical distribution, enable the identification of specific versus shared tanycyte markers and subgroup-specific versus general tanycyte functions. We show that fasting dynamically shifts gene expression patterns along the 3V, leading to a spatial redistribution of cell type-specific responses. Altogether, we show that changes in energy status induce metabolic and functional switches in tanycyte subpopulations, providing insights into molecular and functional diversity and plasticity within the tanycyte population.

Tanycyte, the neuron whisperer.

Reciprocal communication between neurons and glia is essential for normal brain functioning and adequate physiological functions, including energy balance. In vertebrates, the homeostatic process that adjusts food intake and energy expenditure in line with physiological requirements is tightly controlled by numerous neural cell types located within the hypothalamus and the brainstem and organized in complex networks. Within these neural networks, peculiar ependymoglial cells called tanycytes are nowadays recognized as multifunctional players in the physiological mechanisms of appetite control, partly by modulating orexigenic and anorexigenic neurons. Here, we review recent advances in tanycytes' impact on hypothalamic neuronal activity, emphasizing on arcuate neurons.

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

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.