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

Proceedings of the National Academy of Sciences of the United States of America 2012 Mar 13

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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.

Citation

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, Laura G Sánchez-Lozada, David T Bonthron, Yuri Y Sautin, Richard J Johnson. Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice. Proceedings of the National Academy of Sciences of the United States of America. 2012 Mar 13;109(11):4320-5