Although typically associated with excess weight, obesity and type 2 diabetes, up to 20% of individuals with MAFLD are considered to be lean.[3]<\/a><\/p>\n Sydney University PhD student Mohammad Alarabi is first author of the study, published today in\u00a0Hepatology International.\u00a0<\/em>He says, \u201cDespite being healthier overall than their overweight or obese counterparts, lean people with MAFLD have a worse long-term prognosis. We set out to understand the mechanisms that cause this seemingly contradictory outcome.\u201d<\/p>\n The research team focused their efforts on telomeres \u2013 protective structures found on the end of chromosomes. Mohammad Alarabi says, \u201cTelomeres protect the end of a chromosome from becoming frayed and tangled.<\/p>\n \u201cEach time a cell divides, some of the telomeres get cut off. Eventually, the telomeres become so short that the cell dies.\u201d<\/p>\n The shortening of telomeres is associated with increased morbidity and mortality in several diseases.<\/p>\n Mohammad Alarabi explains, \u201cWe hypothesised that telomere loss increases in times of substantially higher energy demands or metabolic stress. Long-term, this could lead to increased cell death and poorer outcomes.\u201d<\/p>\n In this study, the research team demonstrated that growth\/differentiation factor-15 (GDF-15), a protein that helps to regulate a cell\u2019s response to injury, is reduced in lean individuals with MAFLD.<\/p>\n As the cells try to adapt to this reduction in GDF-15, it results in an increase in molecules known as endogenous reactive oxygen species (ROS). An increase in ROS can cause damage to telomeres and may result in cell death.<\/p>\n \u201cIt is the combination of a decrease in GDF-15 and increase in ROS that leads to a more rapid loss of telomeres,\u201d says Mohammad Alarabi.<\/p>\n \u201cWe have been able to demonstrate that the shortening of telomeres can, in part, explain the increased mortality of lean individuals with MAFLD.<\/p>\n \u201cWe say \u201cin part\u201d because there is another factor that we believe has an impact on mortality rates.<\/p>\n \u201cAs the name suggests, \u201cfatty liver\u201d is usually associated with excess weight and obesity. Many health professionals do not consider that a lean person potentially has a \u201cfatty liver\u201d. This means that many lean individuals are diagnosed with MAFLD much later than their non-lean counterparts, which results in delayed treatment. This could also partially explain the increased mortality of lean individuals with MAFLD,\u201d Mohammad Alarabi says.<\/p>\n The next step for the research team is to look for treatments that could stop the increase in ROS, reducing telomere loss and increasing survival rates for lean people with MAFLD.<\/p>\n Mohammad Alarabi adds, \u201cWe also hope to develop a biomarker that could identify increased ROS, and improve early detection of MAFLD in lean individuals.\u201d<\/p>\n![\"\"](\"\/wp-content\/uploads\/2024\/09\/043528aa-310a-40ba-a743-3d84e3581d24.jpg\")
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