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Title: Amino acid sensing in hypothalamic tanycytes via umami taste receptors
Author: Lazutkaite, Greta
ISNI:       0000 0004 7431 7203
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2018
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Energy homeostasis is controlled in the hypothalamus. Hypothalamic tanycytes are a type of glial cell that lie in the wall of the third ventricle, between ventricular CSF and the key nuclei controlling feeding, and are potentially linked to this regulation. Tanycytes have been found to express sweet taste receptors; similar receptors exist for amino acids and could be present in tanycytes. Therefore, the aims of this work were to understand the tanycyte amino acid signalling process, determine the impact of diet on tanycyte function, and link tanycytes to energy homeostasis. Using ratiometric Ca2+ imaging, I showed that tanycytes responded to amino acids; the responses also involved ATP release via pannexin 1 and CalHM1 from tanycyte cell bodies and down their processes towards the parenchyma. As IMP increased the amplitude of tanycyte responses to some amino acids, one of the receptors is Tas1r1/Tas1r3. The Tas1r1 subunit was expressed in mouse tanycytes, and Tas1r1-null mice showed sex-specific altered responses to arginine and lysine. mGluR4 antagonist MAP4 reduced the responses to alanine, and mGluR4 was shown to be present in mouse tanycytes. Tas1r1/Tas1r3 and mGluR4 are therefore two of the receptors responsible for tanycyte amino acid signalling. Fasting and essential amino acid deprivation increased tanycyte sensitivity to alanine. Essential amino acid-deprived diet also reduced the intake of an alanine-enriched drink. While amino acid-imbalanced diets did not have strong effects on mouse metabolism over 24 hours, increasing dietary alanine content reduced feeding and increased metabolism in the light phase. These results demonstrate for the first time that tanycytes can detect amino acids, and that they do so via two different pathways, similarly to taste receptor cells in the tongue. Tanycytes can send ATP signals to inform the hypothalamus about nutrient availability. The data also show that tanycyte amino acid sensitivity is diet-dependent. High alanine food has a satiating effect, which could be partially mediated by tanycytes, although a direct link cannot be confirmed at this stage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology