Scientists Explain Why Artificial Sweeteners Don’t Quench Our Appetite for Sugar

We identified a key gut-to-brain circuit responsible for our unquenchable sugar appetite. Interview with:
Alexander Sisti, MD/PhD Candidate
Zuker Lab
Columbia University

suga  What is the background for this study? 

Response: Our lab has studied the biology of mammalian taste for over two decades. Previous work has identified the receptors for all five basic taste qualities (sweet, sour, bitter, salty, umami).

In the course of these studies, we generated mice lacking sweet receptors (i.e. “sweet-blind”). Unexpectedly, we observed that these animals could eventually learn to identify and develop a preference for a sugar-containing bottle—even though they could not taste it. This was not true for artificial sweeteners. This led us to hypothesize that there was something about the sugar that made the animals feel good and want more of it.

We set out to identify the brain circuits underlying our insatiable appetite for sugar which could operate independently from the taste system. So, we searched the brain for areas activated by sugar but not artificial sweeteners and areas that responded to sugar in the sweet-blind animals. We wanted to identify where the sugar signal was coming from.  What are the main findings?

Response: Our work revealed that sugar activates a selective circuit from the gut to the brain. This pathway is responsible for our “wanting” of sugar. It does not respond to artificial sweeteners and operates completely independently from the classical tongue-to-brain taste system (which mediates “liking” of all sweet substances, including artificial sweeteners). The discovery of this new circuit fundamentally changes the way we think about the action of sugar in the brain. What should readers take away from your report?

Response: Our most significant findings are:

  1. We identified a key gut-to-brain circuit responsible for our unquenchable sugar appetite.
  2. We demonstrate that silencing this circuit is able to completely abolish development of sugar preference. Essentially, we were able to create “sugar-blind” animals insensitive to sugar craving. Given the extraordinary impact of sugar on the global epidemic of obesity, metabolic syndrome and diabetes, identifying new strategies to curb sugar consumption could have a meaningful impact on human health.
  3. Our results explain why artificial sweeteners have failed in reducing our appetite for sugar, as they cannot activate this gut-brain circuit.


Hwei-Ee Tan, Alexander C. Sisti, Hao Jin, Martin Vignovich, Miguel Villavicencio, Katherine S. Tsang, Yossef Goffer, Charles S. Zuker. The gut–brain axis mediates sugar preferenceNature, 2020; DOI: 10.1038/s41586-020-2199-7


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Last Updated on April 16, 2020 by weightcontrol