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Cell Metab. 2019 Aug 26. pii: S1550-4131(19)30433-4. doi: 10.1016/j.cmet.2019.08.004. [Epub ahead of print]

Tanycytes Regulate Lipid Homeostasis by Sensing Free Fatty Acids and Signaling to Key Hypothalamic Neuronal Populations via FGF21 Secretion.

Author information

1
Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland. Electronic address: sarah.geller.phd@gmail.com.
2
Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland.
3
Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland.
4
Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland; Institute of Sports Sciences, University of Lausanne, Lausanne 1005, Switzerland; Service of Endocrinology, Diabetology, and Metabolism, Department of Medicine, Lausanne University Hospital, Lausanne 1011, Switzerland.
5
Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
6
Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland; Centre de Résonance Magnétique des Systèmes Biologiques, UMR5536 CNRS, LabEx TRAIL-IBIO, Université de Bordeaux, Bordeaux Cedex 33760, France. Electronic address: luc.pellerin@unil.ch.

Abstract

The hypothalamus plays a key role in the detection of energy substrates to regulate energy homeostasis. Tanycytes, the hypothalamic ependymo-glia, are located at a privileged position to integrate multiple peripheral inputs. We observed that tanycytes produce and secrete Fgf21 and are located close to Fgf21-sensitive neurons. Fasting, likely via the increase in circulating fatty acids, regulates this central Fgf21 production. Tanycytes store palmitate in lipid droplets and oxidize it, leading to the activation of a reactive oxygen species (ROS)/p38-MAPK signaling pathway, which is essential for tanycytic Fgf21 expression upon palmitate exposure. Tanycytic Fgf21 deletion triggers an increase in lipolysis, likely due to impaired inhibition of key neurons during fasting. Mice deleted for tanycytic Fgf21 exhibit increased energy expenditure and a reduction in fat mass gain, reminiscent of a browning phenotype. Our results suggest that tanycytes sense free fatty acids to maintain body lipid homeostasis through Fgf21 signaling within the hypothalamus.

KEYWORDS:

Fgf21; browning; glial; hypothalamus; liver; monocarboxylates; oleate; palmitate; tanycyte; white adipose tissue

PMID:
31474567
DOI:
10.1016/j.cmet.2019.08.004

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