A relative deficiency of lysosomal acid lypase activity characterizes non-alcoholic fatty liver disease

Francesco Tovoli, Lucia Napoli, Giulia Negrini, Sergio D’Addato, Giulia Tozzi, Jessica D’Amico, Fabio Piscaglia, Luigi Bolondi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.

Original languageEnglish
Article number1134
JournalInternational Journal of Molecular Sciences
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

Sterol Esterase
Lipases
liver
Liver
acids
Acids
hepatitis
viruses
Hepacivirus
Blood
Viruses
blood
blood cell count
lipid metabolism
Pancytopenia
hypertension
Non-alcoholic Fatty Liver Disease
leukocytes
Hematologic Tests
Portal Hypertension

Keywords

  • Liver cirrhosis
  • Lysosomal acid lipase
  • Non-alcoholic fatty liver disease
  • Steatohepatitis
  • Steatosis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

A relative deficiency of lysosomal acid lypase activity characterizes non-alcoholic fatty liver disease. / Tovoli, Francesco; Napoli, Lucia; Negrini, Giulia; D’Addato, Sergio; Tozzi, Giulia; D’Amico, Jessica; Piscaglia, Fabio; Bolondi, Luigi.

In: International Journal of Molecular Sciences, Vol. 18, No. 6, 1134, 01.06.2017.

Research output: Contribution to journalArticle

Tovoli, Francesco ; Napoli, Lucia ; Negrini, Giulia ; D’Addato, Sergio ; Tozzi, Giulia ; D’Amico, Jessica ; Piscaglia, Fabio ; Bolondi, Luigi. / A relative deficiency of lysosomal acid lypase activity characterizes non-alcoholic fatty liver disease. In: International Journal of Molecular Sciences. 2017 ; Vol. 18, No. 6.
@article{7ad0dce64523432bb8ffcdff533eb05d,
title = "A relative deficiency of lysosomal acid lypase activity characterizes non-alcoholic fatty liver disease",
abstract = "Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.",
keywords = "Liver cirrhosis, Lysosomal acid lipase, Non-alcoholic fatty liver disease, Steatohepatitis, Steatosis",
author = "Francesco Tovoli and Lucia Napoli and Giulia Negrini and Sergio D’Addato and Giulia Tozzi and Jessica D’Amico and Fabio Piscaglia and Luigi Bolondi",
year = "2017",
month = "6",
day = "1",
doi = "10.3390/ijms18061134",
language = "English",
volume = "18",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "6",

}

TY - JOUR

T1 - A relative deficiency of lysosomal acid lypase activity characterizes non-alcoholic fatty liver disease

AU - Tovoli, Francesco

AU - Napoli, Lucia

AU - Negrini, Giulia

AU - D’Addato, Sergio

AU - Tozzi, Giulia

AU - D’Amico, Jessica

AU - Piscaglia, Fabio

AU - Bolondi, Luigi

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.

AB - Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.

KW - Liver cirrhosis

KW - Lysosomal acid lipase

KW - Non-alcoholic fatty liver disease

KW - Steatohepatitis

KW - Steatosis

UR - http://www.scopus.com/inward/record.url?scp=85019717790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019717790&partnerID=8YFLogxK

U2 - 10.3390/ijms18061134

DO - 10.3390/ijms18061134

M3 - Article

AN - SCOPUS:85019717790

VL - 18

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 6

M1 - 1134

ER -