The rise in
fructose consumption, and its correlation with symptoms of
metabolic syndrome (MBS), has highlighted the need for a better understanding of
fructose metabolism. To that end, valid rodent models reflecting the same metabolism as in humans, both biochemically and physiologically, are critical. A key to understanding any type of metabolism comes from study of disease states that affect such metabolism. A serious defect of
fructose metabolism is the autosomal recessive condition called
hereditary fructose intolerance (HFI), caused by mutations in the human
aldolase B gene (Aldob). Those afflicted with HFI experience liver and kidney dysfunction after
fructose consumption, which can lead to death, particularly during infancy. With very low levels of
fructose exposure, HFI patients develop non-alcoholic
fatty acid liver disease and
fibrosis, sharing liver pathologies also seen in MBS. A major step toward establishing that
fructose metabolism in mice mimics that of humans is reported by investigating the consequences of targeting the mouse
aldolase-B gene (Aldo2) for deletion in mice (Aldo2(-/-)). The Aldo2(-/-) homozygous mice show similar pathology following exposure to
fructose as humans with HFI such as
failure to thrive,
liver dysfunction, and potential morbidity. Establishing that this mouse reflects the symptoms of HFI in humans is critical for comparison of rodent studies to the human condition, where this food source is increasing, and increasingly controversial. This animal should provide a valuable resource for answering remaining questions about
fructose metabolism in HFI, as well as help investigate the biochemical mechanisms leading to liver pathologies seen in MBS from high
fructose diets.