Dr. Fanny Langlet, Group Leader (Ambizione)

Fanny Langlet received her PhD in 2013 from the University of Lille for her work carried out in the group of Vincent Prévot about the role of tanycytes in the regulation of energy balance. For her postdoctoral training, she joined the laboratory of Dr. Domenico Accili in 2014 to study the transcriptional and epigenetic regulation of key hepatic enzymes involved in the maintenance of glucose homeostasis. In October 2017, she joined the Center for Integrative Genomics at the University of Lausanne as SNSF Ambizione fellow to investigate subpopulation-specific molecular mechanisms underlying glucose-sensing by tanycytes.

Research summary

An adequate balance between energy supply and energy expenditure is essential to ensure healthy life. To maintain this energy homeostasis, the brain is engaged in continuous dialogue with peripheral tissues in order to regulate the fraction of energy which enters the organism (food intake) and that which leaves the organism (energy expenditure). To exert this role, the brain is able to sense metabolic signals -including hormones and nutrients - which convey information about the nutritional status and body energy stores, and respond responds via efferent regulatory signals –channeled mostly via the endocrine and the autonomic nervous system– to restore energy balance. In the last decade, it has become clear that tanycytes –hypothalamic glial cells lining the bottom of the third ventricle– are in prime position to detect variations of nutrient and hormone levels. Our research aims at understanding the molecular mechanisms underlying tanycyte fuel sensing and its impact on the regulation of energy balance.

Deciphering tanycyte heterogeneity

Tanycyte cell population shows a complex heterogeneity which is not fully comprehended yet. Depending on their location along the third ventricle, tanycytes display different morphological, structural, genetic and functional properties. We seek to deeper characterize their transcriptional heterogeneity using FACS associated single-cell RNAseq in order to identify new tanycyte subtypes, markers and functions.

Role of tanycyte glucokinase in the regulation of energy balance

Among different mechanisms proposed to explain how tanycytes sense glucose, our group study the glucokinase-dependent hypothesis in which the glucokinase-dependent metabolism of glucose leads to ATP production. We investigate which tanycyte subgroups are associated to this mechanism, the role of glucokinase for tanycyte functions as well as its impact on neuronal activity and mice physiology.

Representative Publications

Langlet F. Targeting tanycytes: balance between efficiency and specificity. In press in Neuroendocrinology.

Langlet F. Tanycyte Gene Expression Dynamics in the Regulation of Energy Homeostasis. Front Endocrinol (Lausanne). 2019 May 7;10:286. doi: 10.3389/fendo.2019.00286.

Balland E, Dam J*, Langlet F*, Caron E*, Steculorum S*, Messina A, Rasika S, Falluel-Morel A, Anouar Y, Dehouck B, Trinquet E, Jockers R, Bouret SG, Prevot V. Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab. 2014 Feb 4; 19(2):293-301. doi: 10.1016/j.cmet.2013.12.015. *Equal contribution (Cell Metab Previews p. 173-175)

Langlet F, Mullier A, Bouret SG, Prévot V, Dehouck B. Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain. J Comp Neurol. 2013 Oct 15; 521(15):3389-405. doi: 10.1002/cne.23355.

Langlet F, Levin BE*, Luquet S*, Mazzone M*, Messina A*, Dunn-Meynell AA, Balland E, Lacombe A, Mazur D, Carmeliet P, Bouret SG, Prevot V, Dehouck B. Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab. 2013 Apr 2; 17(4):607-17. doi: 10.1016/j.cmet.2013.03.004. *Equal contribution (Cell Metab Previews p. 467-468)

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Fanny Langlet

fanny.langlet@unil.ch

Tel: +41 21 692 3983