Growth Differentiation Factor 15 (GDF-15) Levels Associated with the Presence and Severity of NAFLD

Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by excess fat deposition in the liver, and it is strongly associated with systemic metabolic disorders such as obesity, insulin resistance, diabetes, and dyslipidemia, representing the hepatic manifestation of metabolic syndrome. NAFLD affects more than 25% of the population and could lead to extra-hepatic complications, including cardiovascular disease, which is one of its major causes of mortality. We utilized novel molecules that might reflect inflammation and dysmetabolic processes such as intact (H202D allele non-detectable) and total (measured irrespectively of the allele presence) GDF-15 to explore whether these molecules are involved in NAFLD pathophysiology. In addition, we explored whether adjusting GDF-15 for leptin and adiponectin, as molecules reflecting fat-mass and insulin-sensitivity, respectively, could alter GDF-15. In the first case-control study we analyzed biopsy-diagnosed NAFLD subjects (NAFL n=109, NASH n=163) and compared them to lean controls (n=33) and obese controls (n=31). In the second study we analyzed lean controls (n=7), obese controls (n=7) vs. NAFLD subjects (n=13). We present for the first time that total and intact GDF-15 levels are higher in NAFLD than in controls, particularly in NASH subjects and those with severe fibrosis. These results were largely confirmed within the first and second study. In conclusion, the metabolic/inflammatory hormones total and intact GDF-15 are related to NAFLD pathophysiology and should be further studied as a biomarker or possible treatment targets for this condition.