Here at EpiGenie, we don’t like to sugar-coat our headlines. The sickly-sweet truth is that fructose can be pretty bad for your health. Fructose has become a common additive in many foods in the form of high-fructose corn syrup. Sugary drinks are one of the most common forms. Heavy soft drink consumption is linked to heart disease, stroke, diabetes, and cognitive decline. However, the gestational effect of high fructose consumption remains unclear.
Koji Ohashi’s group at Tottori University (Japan) wanted to investigate whether gestational fructose had long-term epigenetic consequences in the brain. This group previously showed that in rats, excess maternal fructose consumption alters hippocampal gene expression in offspring. Others have shown that excess maternal fructose consumption impairs hippocampal-dependent learning and memory. However, no previous study has examined the role of epigenetics in mediating these effects. Ohashi’s group focused on the hippocampus, since it is known to be highly sensitive to prenatal/early life stress. Environmental stress and malnutrition can cause inflammation, apoptosis, and reduced levels of neurotrophic factors resulting in decreased hippocampal neurogenesis. The authors hypothesised that a maternal high fructose diet would result in altered brain-derived neurotrophic factor (Bdnf) expression & methylation, reduced neurogenesis, and impaired hippocampal-dependent learning in offspring. They provided rats with access 20% fructose or 20% glucose compared to a water control during gestation and lactation.
Here’s what they found when examining juvenile (day 21) and adult (day 60) offspring:
- High fructose offspring spend significantly less time exploring a novel object than either other group as adults, suggesting impaired learning
- Similarly, in a fear conditioning task, the high fructose offspring exhibit less freezing behavior in the contextual task than either other group, but there are no differences in the auditory-cued fear memory task, implying impaired hippocampal- but not amygdala-dependent learning
- High fructose offspring (but not glucose) have 20% fewer BrdU/NeuN hippocampal neurons, while there is no significant difference in apoptosis, suggesting reduced neurogenesis
- qPCR revealed that the BDNF gene expression was reduced in high fructose (but not glucose) juvenile offspring but only in high fructose males at adulthood
- Pyrosequencing uncovered that the CREB binding site in the Bdnf promoter is hypermethylated in juvenile and adult male fructose-exposed offspring. A luciferase assay showed that deletion of the affected CG sites affects BDNF gene expression, suggesting a functional relationship
Taken together, the findings demonstrate that gestational fructose leads to long-term changes in the epigenetic regulation of Bdnf, which lead to decreased cognitive performance and reduced adult hippocampal neurogenesis. If high gestational fructose acts as an epigenetic disruptor of neurogenesis, it would add yet another entry to the long list of reasons to be sure as sugar to avoid it.
Catch the rest of this sugar rush over at FASEB, January 2018