4th September 2019
Gene therapy reduces obesity and reverses type 2 diabetes in mice
Scientists have used CRISPR to switch off a fat storage gene in mice, resulting in a 20% weight loss and improved insulin resistance.
Credit: Jee Young Chung
The obesity epidemic affects 14% of the world's population, a figure that is forecast to reach 22% by 2045, if trends continue. Obesity-related diseases – including heart disease, stroke, type 2 diabetes, and cancer – are a leading cause of preventable death. Obesity is caused by a combination of genetic and environmental factors, confounding the development of anti-obesity drugs, which exhibit severe off-target effects. In a new study, published by the journal Genome Research, scientists developed a gene therapy that specifically reduces fat tissue and reverses obesity-related metabolic disease in obese mice.
To overcome the side effects of current anti-obesity drugs, Jee Young Chung and colleagues from Hanyang University in Seoul, South Korea, developed a specific gene silencing therapy against a fatty acid metabolism gene, Fabp4. The researchers used a CRISPR interference system, involving a Cas9 protein and single guide RNA targeted to white adipocytes with a tissue-specific fusion peptide.
Little toxicity to the cells was observed, as the molecule complex decreased the expression of Fabp4 and reduced lipid storage in adipocytes. Chung and colleagues tested their therapy on obese mice, fed a diet high in fat leading to obesity and insulin resistance. This resulted in a 20% reduction of body weight and improved insulin resistance and inflammation after just six weeks of treatment. Additional systemic improvements were observed, including a reduction in fatty lipid deposition in the liver and reduced circulating triglycerides.
For comparison, the current standard FDA-approved treatment shows just 5% of body weight loss after a year of treatment in humans. However, while this new genetic therapy displays promising results in mice, the researchers emphasise that further studies are required before it can be used in clinical treatment against human disease. Importantly, the team points out, this work highlights recent advances in precision gene editing technology, which could be translated to other types of therapies.