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Cited by 369Liver Disease Diagnosis and TreatmentCholesterol and Lipid MetabolismCancer, Lipids, and Metabolism

The DOI matches its Crossref record; 38 of the 39 references it cites were found in a registry or an index.

Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH

Caballero, Francisco, Fernández, Anna, De Lacy, Antonio M., Fernández-Checa, Jose C., Caballería, Juan, García-Ruiz, Carmen·2009·Journal of Hepatology
DOI 10.1016/j.jhep.2008.12.016
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Abstract

Background/aims Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains unknown. Due to the emerging role of free cholesterol (FC) in NAFLD, our aim was to examine the correlation between FC accumulation in patients with NAFLD and the expression of enzymes that regulate cholesterol homeostasis. Methods Filipin staining, indicative of FC accumulation, and real-time PCR analyses were performed in 31 NAFLD patients and in seven controls. Results All NASH patients (n=14) and 4 out of 17 patients with steatosis exhibited filipin staining compared to controls (0 out of 7 subjects with normal liver histology and BMI). Sterol regulatory element-binding protein-2 (SREBP-2) mRNA levels were 7- and 3-fold higher in NASH and steatosis patients, respectively, compared to controls. Since hydroxymethylglutaryl-CoA (HMG-CoA) reductase is the key enzyme in cholesterol synthesis and transcriptionally controlled by SREBP-2 we measured its mRNA levels, being 3- to 4-fold higher in NAFLD compared to controls, without any difference between NASH and steatosis patients. Fatty acid synthase (FAS) and SREBP-1c expression were not significantly induced in NAFLD, while ATP-binding cassette sub-family G member 1 (ABCG1), a transporter involved in cholesterol egress, and acyl-CoA-cholesterol acyltransferase mRNA levels were modestly increased (1.5- to 2.5-fold, p<0.05), regardless of fibrosis. Interestingly, mRNA levels of steroidogenic acute regulatory protein (StAR), a mitochondrial-cholesterol transporting polypeptide, increased 7- and 15-fold in steatosis and NASH patients, respectively, compared to controls. Conclusions FC increases in NASH and correlates with SREBP-2 induction. Moreover, StAR overexpression in NASH suggests that mitochondrial FC may be a player in disease progression and a novel target for intervention.

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Metadata

Authors
Caballero, F., Fernández, A., De Lacy, A. M., Fernández-Checa, J. C., Caballería, J., & García-Ruiz, C.
Affiliations
Consejo Superior de Investigaciones Científicas (ES)
ORCID
Caballería, Juan
Venue
Journal of Hepatology
Publisher
Elsevier BV
Published
2009-04
Volume
50
Issue
4
Pages
789-796
ISSN
0168-8278 (ISSN-L)
DOI
10.1016/j.jhep.2008.12.016
OpenAlex
W2010101404
Cited by
368
References
39
Citations by year
2026: 9 · 2025: 21 · 2024: 25 · 2023: 26 · 2022: 18 · 2021: 24 · 2020: 28 · 2019: 18 · 2018: 27 · 2017: 24 · 2016: 30 · 2015: 20 · 2014: 21 · 2013: 22 · 2012: 15
FWCI
12.37
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
National Institute on Alcohol Abuse and Alcoholism (P50-AA11999, P50AA011999)
Topics
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, free cholesterol, SREBP2, steroidogenic acute regulatory protein, cholesterol homeostasis, HMG-CoA reductase, ABCG1, acyl-CoA:cholesterol acyltransferase, fatty acid synthase, SREBP-1c, mitochondrial cholesterol transport, steatosis, fibrosis
MeSH terms
ATP Binding Cassette Transporter, Subfamily G, Member 1, Steroidogenic Acute Regulatory Protein, Adult, Animals, Cholesterol, Fatty Liver, Female, Filipin, Humans, Hydroxymethylglutaryl CoA Reductases, Male, Middle Aged, Obesity, Morbid, Phosphoproteins, RNA, Messenger, DNA Primers, Mice, Knockout, ATP-Binding Cassette Transporters, Reverse Transcriptase Polymerase Chain Reaction, Diabetes Complications, Mice, Sterol Regulatory Element Binding Protein 1, Sterol Regulatory Element Binding Protein 2

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