ESPE Yearbook of Paediatric Endocrinology

Nature, 2020. 580, 511–516.https://www.nature.com/articles/s41586-020-2199-7

The authors identify in mice a population of neurons in the vagal ganglia and brainstem that are activated by the direct delivery of sugar but not artificial sweeteners to the gut. They genetically engineered changes in this gut-to-brain circuit. Silencing of synaptic activity in this circuit prevented the behavioural preference for sugar. Conversely, by chemogenetic activation of this circuit, they could create preferences to alternative stimuli.

Sugar, the simple carbohydrate, provides our most immediate source of dietary energy and most species have evolved to recognise and favour its consumption. Specific sweet taste receptors in our mouths provide an immediate hard-wired signaling route to our brains. But our responses to sugar are more complex, including longer-term effects on brain centres for reward, pleasure and preferences. In mice, artificial sweeteners are less effective than sugars in generating long-term preferences, despite their stronger binding affinity to sweet taste receptors and similar short-term appeal (1). Furthermore, taste receptor-knockout mice retain a preference for sugars, indicating other post-ingestive mechanisms.

Here the authors identify a fascinating new circuit that links post-ingestive sugar-sensing to the brain via the vagal pathway. They identified sodium–glucose-linked transporter-1 (SGLT1) as a key link in activating this circuit. SGLT1 is the principal glucose transporter in the gut, corresponding to the role of SGLT2 in the renal proximal tubule. It seems conceivable that SGLT1 inhibitors could have health benefits, similar to the exciting evidence that is currently being generated on SGLT2 inhibitors. However, losing our euphoric buzz to sugars may not be an appealing prospect for many people. So alternatively, the authors suggest that new artificial sweeteners might be developed that can activate both our tongues and our gut sensors.

Reference: 1. Sclafani A, Zukerman S & Ackroff K. Postoral glucose sensing, not caloric content, determines sugar reward in C57BL/6J mice. Chem. Senses 40, 245–258 (2015).