Cell Metabolism
Volume 30, Issue 4, 1 October 2019, Pages 833-844.e7
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Short Article
Tanycytes Regulate Lipid Homeostasis by Sensing Free Fatty Acids and Signaling to Key Hypothalamic Neuronal Populations via FGF21 Secretion

https://doi.org/10.1016/j.cmet.2019.08.004Get rights and content
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Highlights

  • Hypothalamic tanycytes synthesize and secrete Fgf21 under nutritional stress

  • Palmitate oxidation in tanycytes triggers Fgf21 expression via the ROS/p38-MAPK pathway

  • Deletion of tanycytic Fgf21 reduces fat depot size and promotes energy expenditure

  • Deletion of tanycytic Fgf21 promotes lipolysis and browning of WAT

Summary

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
hypothalamus
tanycyte
palmitate
browning
white adipose tissue
glial
liver
oleate
monocarboxylates

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Present address: Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Center for Systems Medicine, Suzhou, China

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