How Fructose Inudces the Metabolic Syndrome

Byron's Comments:

A helpful study explaining how excess frucose consumption can lead to disease.

Study Title:

Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice

Study Abstract:

Fructose intake from added sugars correlates with the epidemic rise in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Fructose intake also causes features of metabolic syndrome in laboratory animals and humans. The first enzyme in fructose metabolism is fructokinase, which exists as two isoforms, A and C. Here we show that fructose-induced metabolic syndrome is prevented in mice lacking both isoforms but is exacerbated in mice lacking fructokinase A. Fructokinase C is expressed primarily in liver, intestine, and kidney and has high affinity for fructose, resulting in rapid metabolism and marked ATP depletion. In contrast, fructokinase A is widely distributed, has low affinity for fructose, and has less dramatic effects on ATP levels. By reducing the amount of fructose for metabolism in the liver, fructokinase A protects against fructokinase C-mediated metabolic syndrome. These studies provide insights into the mechanisms by which fructose causes obesity and metabolic syndrome.

From press release:

A group of scientists from across the world have come together in a just-published study that provides new insights into how fructose consumption results in obesity and metabolic syndrome, which can lead to diabetes. In this study which was performed in lab animals, researchers found that fructose can be metabolized by an enzyme that exists in two forms. One form appears to be responsible for causing how fructose causes fatty liver, obesity, and insulin resistance. The other form may actually protect animals from developing these features in response to sugar.

These studies may provide important insights into the cause of the prediabetic condition known as “metabolic syndrome,” which currently affects more than one-quarter of adults in the United States.
The study, “Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice” was just published in the journal Proceedings of the National Academy of Sciences. Richard Johnson, MD, the senior author of the study and Chief of the Division of Renal Diseases and Hypertension at the University of Colorado School of Medicine said the findings are significant because we now have a better understanding of how fructose causes obesity and other illnesses.
“These studies provide new insights into how fructose may contribute to the development of obesity and diabetes. In particular, the identification of contrasting roles for two enzymes that are involved in fructose metabolism was surprising and could be important in understanding why some individuals may be more sensitive to the metabolic effects of fructose than others.”
Previous research has shown that fructose intake in added sugars such as sucrose and high fructose corn syrup is strongly linked to the epidemic rise in obesity and nonalcoholic fatty liver disease. Fructose intake also causes features of metabolic syndrome in laboratory animals and humans. It is known to cause visceral (organ) fat accumulation and insulin resistance compared to starch based diets even when calories are kept even.
Faculty at the University of Colorado School of Medicine work to advance science and improve care. These faculty members include physicians, educators and scientists at University of Colorado Hospital, Children’s Hospital Colorado, Denver Health, National Jewish Health, and the Denver Veterans Affairs Medical Center. Degrees offered by the CU Denver School of Medicine include doctor of medicine, doctor of physical therapy, and masters of physician assistant studies.

Study Information:

Takuji Ishimoto, Miguel A. Lanaspa, MyPhuong T. Le, Gabriela E. Garcia, Christine P. Diggle, Paul S. MacLean, Matthew R. Jackman, Aruna Asipu, Carlos A. Roncal-Jimenez, Tomoki Kosugi, Christopher J. Rivard, Shoichi Maruyama, Bernardo Rodriguez-Iturbe. Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice Proceedings of the National Academy of Sciences 2012 March vol. 109 no. 11 4320-4325
Division of Renal Diseases and Hypertension at the University of Colorado School of Medicine