OBJECTIVES: Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors with complex anti-oxidative, anti-fibrotic, and anti-inflammatory properties, thus being involved in cardiometabolic disorders. Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome as well. However, the pathophysiological role of PEDF in NAFLD remains largely unknown. We studied here the relationship between serum PEDF levels and various clinical markers of NAFLD in humans. DESIGN AND METHODS: The study involved 194 biopsy-proven NAFLD patients (102 male and 92 female) with a mean age of 51.3±13.8 years. We examined which anthropometric, metabolic and inflammatory variables, and liver steatosis and fibrosis markers are independently associated with serum levels of PEDF. RESULTS: Mean serum levels of PEDF were 16.4±5.7 μg/mL. Univariate analysis revealed that age (inversely), male, body mass index, waist circumference, numbers of white blood cells and platelets, aspartate aminotransferase, alanine aminotransferase, fasting plasma glucose, glycated hemoglobin, uric acid, procollagen type III N-terminal peptide (P-III-P), subcutaneous fat areas, visceral fat areas and liver to spleen density ratio in computed tomography, the presence of diabetes and medication for hyperlipidemia were significantly associated with serum levels of PEDF. In multiple stepwise regression analysis, age (p<0.01, inversely), male (p<0.05), waist circumference (p<0.01), white blood cell number (p<0.05), P-III-P (p<0.05), and the presence of diabetes (p<0.05) and medication for hyperlipidemia (p<0.01), were independently correlated to serum levels of PEDF (R(2)=0.285). CONCLUSIONS: The present study reveals that serum levels of PEDF are independently associated with P-III-P levels, suggesting that PEDF level is a novel biomarker of liver fibrosis in patients with NAFLD.
OBJECTIVES:Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors with complex anti-oxidative, anti-fibrotic, and anti-inflammatory properties, thus being involved in cardiometabolic disorders. Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome as well. However, the pathophysiological role of PEDF in NAFLD remains largely unknown. We studied here the relationship between serum PEDF levels and various clinical markers of NAFLD in humans. DESIGN AND METHODS: The study involved 194 biopsy-proven NAFLD patients (102 male and 92 female) with a mean age of 51.3±13.8 years. We examined which anthropometric, metabolic and inflammatory variables, and liver steatosis and fibrosis markers are independently associated with serum levels of PEDF. RESULTS: Mean serum levels of PEDF were 16.4±5.7 μg/mL. Univariate analysis revealed that age (inversely), male, body mass index, waist circumference, numbers of white blood cells and platelets, aspartate aminotransferase, alanine aminotransferase, fasting plasma glucose, glycated hemoglobin, uric acid, procollagen type III N-terminal peptide (P-III-P), subcutaneous fat areas, visceral fat areas and liver to spleen density ratio in computed tomography, the presence of diabetes and medication for hyperlipidemia were significantly associated with serum levels of PEDF. In multiple stepwise regression analysis, age (p<0.01, inversely), male (p<0.05), waist circumference (p<0.01), white blood cell number (p<0.05), P-III-P (p<0.05), and the presence of diabetes (p<0.05) and medication for hyperlipidemia (p<0.01), were independently correlated to serum levels of PEDF (R(2)=0.285). CONCLUSIONS: The present study reveals that serum levels of PEDF are independently associated with P-III-P levels, suggesting that PEDF level is a novel biomarker of liver fibrosis in patients with NAFLD.
Authors: Arijeet K Gattu; Andreas L Birkenfeld; Yasuko Iwakiri; Steven Jay; Mark Saltzman; Jennifer Doll; Petr Protiva; Varman T Samuel; Susan E Crawford; Chuhan Chung Journal: Endocrinology Date: 2014-01-23 Impact factor: 4.736