Gene Therapy Shown to Reverse Metabolic Disease in Obese Mice

Gene Therapy Shown to Reverse Metabolic Disease in Obese Mice

A team of researchers at Hanyang University in South Korea have used CRISPR gene therapy to silence a fatty acid metabolism gene and reverse metabolic disease in mice. The gene therapy technique could serve as an alternative to anti-obesity drugs, which have low efficacy and often cause severe side effects such as nausea, dizziness, vomiting, and insomnia.

The drugs act on the gastrointestinal tract and the central nervous system, which are both delicate systems. Using drugs to target these systems and reduce caloric intake can causes problems throughout the body. Due to the severity of the side effects, many individuals choose to stop their treatment.

Tackling obesity is essential for improving the health of a population. Obesity increases the risk of developing cardiovascular disease, diabetes, and cancer. These obesity-related diseases are a leading cause of preventable death. Around half a billion people around the world are obese, many of whom are children.

While there are many cases of obesity caused by environmental factors, obesity can also be caused by genetic factors. Correcting faulty genes could give patients the best possible chance of reducing their weight and greatly improving their health.

The researchers, led by Jee Young Chung, used the CRISPR-Cas9 gene editing tool to silence the Fabp4 fatty acid metabolism gene in white adipocyte cells. The researchers showed there was low toxicity and expression of Fabp4 decreased, which in turn reduced lipid storage in adipocyte cells in the lab and was subsequently tested on obese mice.

After being fed a fat-rich diet, mice became obese and started to develop insulin resistance. Mice in the control group saw no weight loss, whereas mice that received the CRISPR treatment saw repression of Fabp4 and a 20% reduction in body weight 6 weeks following treatment. There was also reduced inflammation, an improvement in insulin resistance, a reduction in circulating triglycerides, and less fatty lipid deposition in the liver.

A 20% reduction in body weight in just 6 weeks is considerable. Treatment with anti-obesity drugs typically result in a loss of 5% of body weight over a period of one year.

The new CRISPR treatment appears to be highly effective in mice, but it will likely be several years before the treatment could be used in humans. Further studies are first required to test the effectiveness and safety of the treatment in humans.

The study is detailed in the paper – Targeted delivery of CRISPR interference system against Fabp4 to white adipocytes ameliorates obesity, inflammation, hepatic steatosis, and insulin resistance – which was recently published in the journal Genome Research. DOI: 10.1101/gr.246900.118

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