The accumulation of fat in muscle tissue is linked to the development of insulin resistance, which can lead to type 2 diabetes.
To identify the mechanisms involved in this process, US researchers used a high-throughput screening method to identify compounds that reduced accumulation of lipid in skeletal muscle cells.
They found a molecule called SBI-477, which deactivates a protein involved in both fat storage and insulin signalling, known as MondoA. In mice fed a high-fat diet, the researchers showed that an SBI-477 analogue could reduce muscle and liver triacylglyceride levels, enhance insulin signalling and improve glucose tolerance. It also induced modest weight loss.
The team, who report their findings in the Journal of Clinical Investigation (online, 8 August 2016)
, say that exploring other molecules that inhibit MondoA could be an avenue for developing drugs to prevent type 2 diabetes.