Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty Liver Disease.
Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation and mechanisms involved in its pathogenesis are not fully explained. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with fatty liver. LAL activity (nmol/spot/h) was measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub-analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed. Median LAL activity was 1.15 (0.95-1.72) in HS. It was significantly reduced in NAFLD [0.78 (0.61-1.01), p < 0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51-0.77), p < 0.001 vs. HS]. Patients with LAL activity below median had higher values of serum total cholesterol (p < 0.05) and LDL-c (p < 0.05), and increased serum liver enzymes (ALT, p < 0.001; AST, p < 0.01; GGT, p < 0.01). At multivariable logistic regression analysis, factors associated with LAL activity below median were ALT (OR: 1.018, 95% CI 1.004-1.032, p = 0.011) and metabolic syndrome (OR: 2.551, 95% CI 1.241-5.245, p = 0.011), whilst statin use predicted a better LAL function (OR: 0.464, 95% CI 0.248-0.866, p = 0.016). Our findings suggest a strong association between impaired LAL activity and NAFLD. A better knowledge of the role of LAL may provide new insights in NAFLD pathogenesis.
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy ; Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Italy.
Francesco
F
Baratta
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy ; Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Italy.
Daniele
D
Pastori
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Maria
M
Del Ben
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy ; Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Italy.
Licia
L
Polimeni
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Giancarlo
G
Labbadia
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy.
Serena
S
Di Santo
Unit for Neuromuscular and Neurodegenerative Diseases, Children's Hospital and Research Institute "Bambino Gesù", Rome, Italy.
Fiorella
F
Piemonte
Unit for Neuromuscular and Neurodegenerative Diseases, Children's Hospital and Research Institute "Bambino Gesù", Rome, Italy.
Giulia
G
Tozzi
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Francesco
F
Violi
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy.
Francesco
F
Angelico
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000201:enzymology*; D002787:Sterol Esterase / Q000378:metabolism*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002787:Sterol Esterase
Lysosomal acid lipase; Metabolic syndrome; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Statins