New hope for sufferers of chronic disease behind weight gain

Melbourne scientists have made a breakthrough discovery that may help sufferers of a debilitating chronic condition in which fat cells multiply uncontrollably.

Melbourne scientists have uncovered the genetic secrets of why some women suffer uncontrollable fat growth, raising hopes drugs may be able to overcome a debilitating chronic condition.

The world-first St Vincent’s Institute discovery has identified an abnormal stem cell involved in lipedema, as well as a gene that causes its sufferer’s fat cells to multiply in a similar way to cancer cells. Lipedema has not previously been recognised as a specific disease, but was considered a form of obesity most commonly impacting the legs and hips in about 11 per cent of women.               However, a five-year study led by Dr Tara Karnezis and her husband Associate Prof Ramin Shayan identified vastly different cells involved in lipedema than in classic obesity, which may now be used as the basis of a screening test and drugs to target the condition’s uncontrolled growth of fat.

In further good news for sufferers, the SVI-led team was also able to adapt a new experimental drug designed to stop the growth of cancer cells to successfully block a protein on lipedema cells and stop abnormal fat growth during lab tests. Lipedema has not previously been recognised as a specific disease, but considered as a form of obesity. “We found in lipedema that the stem cells are quite unique to the disease. They are growing much faster and basically have had their brake removed and, as a result, they grow significantly faster than normal fat cells from obese patients,” Dr Karnezis said. “We also pinpointed genes that could be targeted by drugs — and that’s exactly what we did.           “We treated the lipedema stem cells with these drugs and we were able to bring them back into line again. We started sort of putting on the brakes and they were not able to grow.” After analysing samples from 14 Melbourne lipedema patients and 10 obese patients the Melbourne researchers found significant differences in gene expression, tissue make-up, adipose-derived stem cells and other key elements.                                                                                                                                            Results published in the International Journal of Obesity also reveal that the Bub1 protein - which normally controls the number of cells that grow — misfires in lipedema, signalling uncontrolled fat growth. By using a Bub1 inhibitor called 2OH-BNPP1 they were then able to reapply the brake and stop the uncontrolled growth. Dieting cannot help women lose lipedema weight.                                                                                                           Prof Shayan said the researchers were now pushing to develop a diagnostic screening test for lipedema, as well as an animal model to test drugs with a potential to target Bub1 and halt the disease. If preclinical trials were successful the researchers would then plan for human trials in about five years’ time. Having suffered in pain for decades, both physical and emotional, Lipedema Australia chair Nola Young said she cried with joy when she heard results of the SVI study she participated in.                    “It offers hope,” Ms Young said. “We’ve been dismissed as obese women most of our life. We run a support group for over 500 women and every day we hear of someone who has gone to a doctors ... and they are told to lose weight. “It causes some people eating problems because of the desire to have a better body, but you can diet until the cows (come home) but you will not lose you lipedema weight. “This will mean that later on they might have a cure. There might be a tablet or something they can do to stop this.”

Grant McAurthur Health Editor Herald Sun 24 November 2021

Julie Leeming