A pill to stop obesity may be on the horizon after the discovery of a protein that makes people fat. It would be the ‘holy grail’ of modern medicine – helping reduce the risk of heart disease, cancer, diabetes and even dementia. When the enzyme known as CerS1 (ceramide synthase 1) was blocked in mice they remained lean – even after gorging on high fat food. The Australian team is hopeful the same will apply to humans. They hailed it as a “major step forward” in combating obesity and related diseases. Read More The new prototype drug was tested on mice
Their drug, dubbed PO53, was developed to specifically target the protein because it was believed to be linked to insulin resistance in muscles, liver and fat. Surprisingly, it did not prevent the lab rodents’ levels of blood sugar rising – but lipids instead. These are fats such as cholesterol and triglycerides that increase the risk of heart attacks and other illnesses. The researchers found stopping CerS1 burned them up in skeletal muscle – meaning the mice had less adipose tissue. Corresponding author Professor Nigel Turner, of the University of New South Wales, said: “We anticipated that targeting this enzyme would have insulin-sensitising, rather than anti-obesity effects.
However, since obesity is a strong risk factor for many different diseases including cardiovascular disease and cancer, any new therapy in this space could have widespread benefits.” Prof Turner and colleagues said the results published in Nature Communications were unexpected. They were intending to stop insulin resistance that triggers Type 2 diabetes, the form caused by eating junk food, rather than obesity itself. But it is the first time scientists have been able to develop a drug that successfully destroys lipid producing proteins that cause metabolic disease. This makes it a significant advancement in the understanding and prevention of a range of chronic health conditions. The ceramide proteins are lipids are involved in regulating metabolism. There are six of them. But the role of each is not fully understood.
Inhibition of certain ones is predicted to produce significant benefits for metabolic health, whereas with others it is likely to be detrimental. But drugs with sufficient potency, selectivity and suitable properties for use in a living organism have been elusive – until now. The molecule PO53 stopped the activity of CerS1 in its tracks – reducing fat across the whole body without affecting insulin resistance in mice fed a high-fat diet. Prof Turner and colleagues believe it was due to the drug boosting the oxidation of fatty acids in the muscles of the animals. Co-corresponding author Prof Anthony Don, of the University of Sydney, added: “From here, I would like to develop drugs which target both the CerS1 and 6 enzymes together, and see whether it produces a much stronger anti-obesity and insulin sensitising response.
“Although these drugs need more work before they are suitable for use in the clinic, our work so far has been a very important step in that direction.” In Australia two in three adults are classified as being overweight or obese, about the same as Britain which has the worst rates in Europe. The researchers said the findings open up a potential new therapeutic avenue for the treatment of obesity. But further studies are required to determine if they translate to humans.