Sweet taste signaling functions as a hypothalamic glucose sensor.

Area of Science:

• Neuroscience
• Molecular Biology
• Endocrinology

Background:

• Brain glucosensing is vital for glucose homeostasis and neuronal function.
• Mechanisms of neuronal sensing of extracellular glucose are not fully understood.
• Identification of membrane molecular sensors independent of intracellular metabolism is needed.

Purpose of the Study:

• To investigate the expression of taste receptor genes in the mammalian brain.
• To identify candidate membrane molecular sensors for extracellular glucose.
• To explore the role of taste signaling in brain glucose sensing.

Main Methods:

• Detected expression of taste receptor genes (Tas1r1, Tas1r2, Tas1r3) and G-protein genes in mouse brain regions.
• Utilized in vivo studies to assess regulation of taste-related gene expression by nutritional state.
• Exposed mouse hypothalamic cells to varying glucose and amino acid concentrations, with and without sucralose.

Main Results:

• Taste receptor genes and their protein products were found in nutrient-sensing brain regions like the hypothalamus and hippocampus.
• Hypothalamic expression of Tas1r1 and Tas1r2 increased with food deprivation, unlike in the cortex.
• Low glucose medium increased Tas1r2 expression in hypothalamic cells, reversed by sucralose, indicating non-metabolic signaling.

Conclusions:

• The heterodimeric G-protein coupled sweet receptor T1R2/T1R3 is expressed in the brain.
• This receptor is regulated by nutritional status and responds to glucose independently of metabolism.
• T1R2/T1R3 is a strong candidate for a membrane-bound brain glucosensor involved in glucose homeostasis.