The gene FABP4 is highly active in adipose tissue and known to be a major contributor to obesity and related diseases like type 2 diabetes. Researchers at Hanyang University in Seoul have developed a way to silence the gene using a type of gene-editing technology called CRISPR interference.
When the researchers inhibited FABP4 in white adipose tissue—commonly known as the unhealthy white fat—they observed a reduction in lipid storage.
Then they tried it in mice that had been fed a high-fat diet, injecting them twice a week with the CRISPR interference system. The mice lost 20% of their body weight and showed reductions in inflammation and insulin resistance, the team reported in the journal Genome Research.
Researchers continue to look for weight-loss strategies that might be more effective than the current slate of FDA-approved drugs. Those products—Eisai’s Belviq, Nalpropion’s Contrave and Vivus’ Qsymia—have only been shown to reduce body weight by a small percentage and have therefore struggled to gain much traction in the market.
Last year, Eisai showed that Belviq didn’t increase the incidence of heart attack and stroke in patients, making it the only weight-loss drug be able to boast heart safety. But that hasn’t made much of a difference in jump-starting sales.
Academic groups are investigating the potential of gene therapy in fighting obesity. Last December, a group led by Flinders University in South Australia removed the gene RCAN1 from mice, which accelerated the conversion of white fat into calorie-burning brown fat. When the mice were fed a high-fat diet, they stayed slim.
A team at the University of California, San Francisco is using CRISPR to turn up the volume on genes that help maintain a healthy body weight. They showed last year that when they amplified the activity of SIM1 and MC4R—genes that regulate the feeling of being full—in mice, the animals exhibited more controlled eating behavior than their untreated counterparts. They ended up weighing 40% less than the control mice.
The Hanyang University team is planning further studies to determine how best to translate their gene therapy to people with obesity. They believe that similar “precision gene-editing technology” could be used to treat other diseases, as well, they said in a statement.