Dietary intake of fructose increases purine de novo synthesis: A crucial mechanism for hyperuricemia.
Level 5 - mechanism / opinion, no new human data
Preclinical laboratory experiment in cell culture and mice
PubMed 36601078 · doi:10.3389/fnut.2022.1045805
What was done
Researchers evaluated the mechanisms of fructose-induced hyperuricemia using NCTC 1469 hepatic cell cultures treated with 0 or 25 mM fructose for 24 hours (assessed via RNA-sequencing) and mice fed diets containing 0 or 30 g/kg fructose for 2 weeks. Liver tissue from mice was analyzed using metabolomics, RNA-sequencing, immunofluorescence, and assays measuring the gene/protein expression and activity of purine synthesis enzymes (such as PRPSAP1, PPAT, ADSL, Adss1, IMPDH, and GMPS), mTOR, xanthine oxidoreductase (XOR), uricase, and serum uric acid.
What was found
The abstract reports directional and statistical significance without providing specific numeric values. Fructose treatment significantly increased levels of purine metabolites (AMP, adenine, adenosine, hypoxanthine, and guanine). It significantly upregulated the expression of purine de novo synthesis genes (PRPS2, GART, ATIC, ADSL, Adss1, IMPDH) and catabolism genes (AMPD3, ADA, NT5C, XOR). In mouse livers, fructose increased PRPSAP1 and PPAT gene and protein expression alongside increased mTOR expression, raised XOR expression and activity, reduced uricase expression, and elevated serum uric acid levels.
Why it matters
These findings suggest that fructose promotes hyperuricemia not only by accelerating ATP degradation but also by directly upregulating purine de novo synthesis via mTOR signaling pathways.
Limits
The study was conducted entirely in a rodent cell line and a mouse model; animal counts (n), exact numerical effect sizes, and p-values are omitted from the abstract. Mice possess endogenous uricase (unlike humans), and the high dietary fructose dose may not reflect standard human dietary exposure.
Cited by
- supports Serum uric acid levels exceeding 5 milligrams per deciliter indicate excess dietary fructose consumption and hepatic fructose overload.