A depressing discovery was the fact that the body can make large amounts of fructose. One of the major sources is from high glycemic carbohydrates, such as rice, bread, potatoes, and cereals. When we eat these foods, the glucose in our blood can rise, and when this happens, it can trigger the conversion of glucose to fructose.
The power of this pathway became evident when we put glucose into the drinking water of laboratory mice. The mice drank the glucose water voraciously, and over a few months became very fat and insulin resistant. We had thought that this might simply be due to chronic stimulation of insulin, since one of the actions of insulin is to stimulate fat accumulation. The way we showed this was by studying mice that could not metabolize fructose but who had normal glucose metabolism and insulin responses. When we gave glucose to these mice, they also loved the glucose, but they only gained a modest amount of weight and importantly they were protected from developing diabetes or fatty liver.
In other words, the reason high glycemic carbs cause diabetes and fatty liver, also most of their fattening effects, is not because they stimulate insulin, but rather because the glucose is converted to fructose.
More recently, we gave soft drinks to mice that could not metabolize fructose. As you recall, soft drinks contain both glucose and fructose which are combined to make the sweetener, high fructose corn syrup. Our mice that lacked the ability to metabolize fructose were completely protected from obesity and diabetes despite high intake of both sugars. Again, this shows that the way soft drinks cause obesity is due to their ability to provide fructose.
- Lanaspa, M.A., Ishimoto, T., Li, N., Cicerchi, C., Orlicky, D.J., Ruzycki, P., Rivard, C., Inaba, S., Roncal-Jimenez, C.A., Bales, E.S., Diggle, C.P., Asipu, A., Petrash, J.M., Kosugi, T., Maruyama, S., Sanchez-Lozada, L.G., McManaman, J.L., Bonthron, D.T., Sautin, Y.Y. and Johnson, R.J. (2013) Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome. Nat Commun 4: 2434.
- Andres-Hernando, A., Orlicky, D.J., Kuwabara, M., Ishimoto, T., Nakagawa, T., Johnson, R.J. and Lanaspa, M.A. (2020) Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction. Cell Metab 32: 117-127 e113.