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A new study in Caenorhabditis elegans worms has identified 14 new genes that promote obesity and 3 genes that prevent diet-induced obesity.
Ke et al. report 14 genes that promote obesity and 3 genes that prevent diet-induced obesity when silenced in Caenorhabditis elegans. Image credit: Renée Gordon, FDA.
“We know of hundreds of genetic variants that are more likely to appear in people with obesity and other diseases. But being more likely to appear doesn’t mean causing disease, ”said lead author Dr. Eyleen O’Rourke, a researcher in the Department of Biology and Department of Cell Biology at the University of Virginia, Charlottesvill.
“This uncertainty is a major obstacle to harnessing the power of population genomics to identify targets for treating or curing obesity.”
“To overcome this hurdle, we have developed an automated pipeline to simultaneously test hundreds of genes for a causal role in obesity.”
“Our first set of experiments discovered over a dozen genes that cause and three genes that prevent obesity.”
In the study, Dr. O’Rourke and his colleagues used Caenorhabditis elegans to screen 293 genes associated with obesity in humans, with the aim of defining which genes actually cause or prevent obesity.
This obesity model, coupled with automation and supervised testing assisted by machine learning, allowed them to identify 14 genes that cause obesity and three that help prevent it.
Attractively, they found that blocking the action of the three genes that prevent worms from becoming obese also allows them to live longer and have better neuromotor function.
This is exactly the type of benefit drug developers hope to get from anti-obesity drugs.
“Of course you have to work more. But the indicators are encouraging, ”the researchers said.
“For example, blocking the effect of one of the genes in laboratory mice prevented weight gain, improved insulin sensitivity, and lowered blood sugar.”
“These results – along with the fact that the genes under study were chosen because they were associated with obesity in humans – bode well that the results will be true in humans as well.”
The study was published in the journal PLoS genetics.
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W. Ke et al. 2021. Genes in human obesity loci are causative obesity genes in C. elegans. PLoS Genet 17 (9): e1009736; doi: 10.1371 / journal.pgen.1009736
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