Genomic insertion of ancestral uricase into human liver cells to determine metabolic consequences of pseudogenization
Level 5 - mechanism / opinion, no new human data
In vitro bench study using gene-edited human liver cell models
OpenAlex W4412521796 · doi:10.1038/s41598-025-10551-8
What was done
CRISPR gene editing was used to insert a functional ancestral uricase gene into the genome of human liver cells. Uricase expression, intracellular urate levels, and triglyceride accumulation following fructose exposure were evaluated in both hepatocyte monolayer and spheroid cell culture models.
What was found
The abstract reports no numerical values or statistical metrics. It reports that functional ancestral uricase was successfully expressed in monolayer and spheroid cultures, led to decreased intracellular urate concentrations, and blocked the increase in triglyceride production typically triggered by fructose uptake.
Why it matters
This study provides mechanistic cellular evidence supporting the evolutionary hypothesis that uricase gene inactivation in ancestral primates facilitated increased fat storage in response to fructose.
Limits
The study was conducted entirely in vitro using cultured human hepatocytes, which cannot capture whole-organism metabolic physiology or systemic feedback. Quantitative measurements, statistical effect sizes, and specific cell line details are omitted from the abstract.
Cited by
- supports A mutation in uricase occurred in ancestral great apes and humans approximately 15 million years ago that eliminated uricase activity.