Nature. The neurobiological basis of "sugar addiction".

Sugar taste is one of the most basic sensory perception for human and animals.there is no doubt that the strong preference for sugar (sugar is the main source of human nutrition) plays an important role in human evolution.however, in today's society, excessive intake of sugar may cause many health concerns, such as obesity, diabetes, etc.for the sake of health, people have developed a lot of sugar substitutes for daily food, such as aspartame, acesulfame and other artificial sweeteners.although these artificial sweeteners can "cheat" the sweet receptors of our tongue taste buds to produce sugar like sweetness, their effects can not really replace "real sugar". What is the underlying mechanism behind this? On April 16, 2020, the gut – brain axis mediators sugar preference was published by Charles S. Zuker's research group of Columbia University (Hwei EE Tan and Alexander sisti) in nature. The study revealed that sugar can also pass the gut brain axis pathway (gut brain axis) It plays a role and stimulates the uptake of sugar, while glycogen can not activate the gut brain pathway that specifically recognizes sugar molecules.using c-fos immunohistochemistry and fiber photometry, the researchers found a brain region that only responded to sugar (not glycogen).with the help of trap 2 mouse system developed by Luo Liqun research group of Stanford University, tettox (tetanus toxin light chain) was specifically expressed in the 'sugar neurons'. It was found that when the nerve cells responsive to glucose in the brain region were inhibited, mice no longer craved or preferred sugar.in order to further understand the root cause of sugar signal, the researchers used two kinds of tracing techniques, including injecting pseudo recombinant rabies virus (enva RABV) into the brain and retrograde transport cholera toxin subunit B protein binding fluorophore (CTB adjusted) It is found that these "sugar neurons" receive signals from the vagus nerve and the small intestine, revealing the gut vagus nerve brain pathway.finally, the researchers used chemical genetic technology to express an activated artificially designed receptor (hm3dq) in mouse's' sugar neurons' With the addition of clozapine (clozapine) to drinking water, researchers can control the "sugar neurons" and related behaviors of mice with clozapine small molecule chemicals, so that mice can have a new preference for a beverage taste that has no preference.the first author, Chen Huiyu, said: "when we add a chemical substance to the beverage that can specifically activate the 'sugar neurons', the mice actually act as if they were taking the real sugar molecules!" In conclusion, the researchers not only revealed the different neurobiological mechanisms of glycogen and glucose, but also revealed for the first time a circuit of sugar addiction, namely the gut vagal brain pathway.original link: