A new study in Caenorhabditis elegans worms has identified 14 new genes that promote obesity and 3 genes that prevent diet-induced obesity.
“We know of hundreds of gene variants that are more likely to show up in individuals suffering obesity and other diseases. But more likely to show up does not mean causing the disease,” said senior author Dr. Eyleen O’Rourke, a researcher in the Department of Biology and the Department of Cell Biology at the University of Virginia, Charlottesvill.
“This uncertainty is a major barrier to exploit the power of population genomics to identify targets to treat or cure obesity.”
“To overcome this barrier, we developed an automated pipeline to simultaneously test hundreds of genes for a causal role in obesity.”
“Our first round of experiments uncovered more than a dozen genes that cause and three genes that prevent obesity.”
In the study, Dr. O’Rourke and colleagues used Caenorhabditis elegans to screen 293 genes associated with obesity in humans, with the goal of defining which of the genes were actually causing or preventing obesity.
This obesity model, coupled to automation and supervised machine learning-assisted testing, allowed them to identify 14 genes that cause obesity and three that help prevent it.
Enticingly, they found that blocking the action of the three genes that prevented the worms from becoming obese also led to them living longer and having better neuro-locomotory function.
Those are exactly the type of benefits drug developers would hope to obtain from anti-obesity medicines.
“More work needs to be done, of course. But the indicators are encouraging,” the researchers said.
“For example, blocking the effect of one of the genes in lab mice prevented weight gain, improved insulin sensitivity and lowered blood sugar levels.”
“These results — plus the fact that the genes under study were chosen because they were associated with obesity in humans — bode well that the results will hold true in people as well.”
The study was published in the journal PLoS Genetics.
W. Ke et al. 2021. Genes in human obesity loci are causal obesity genes in C. elegans. PLoS Genet 17 (9): e1009736; doi: 10.1371/journal.pgen.1009736