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Proteomic characterization of high-density lipoprotein particles in patients with non-alcoholic fatty liver disease
- Source :
- Clinical Proteomics, Clinical Proteomics, Vol 15, Iss 1, Pp 1-9 (2018)
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Background Metabolic diseases such as obesity and diabetes are associated with changes in high-density lipoprotein (HDL) particles, including changes in particle size and protein composition, often resulting in abnormal function. Recent studies suggested that patients with non-alcoholic fatty liver disease (NAFLD), including individuals with non-alcoholic steatohepatitis (NASH), have smaller HDL particles when compared to individuals without liver pathologies. However, no studies have investigated potential changes in HDL particle protein composition in patients with NAFLD, in addition to changes related to obesity, to explore putative functional changes of HDL which may increase the risk of cardiovascular complications. Methods From a cohort of morbidly obese females who were diagnosed with simple steatosis (SS), NASH, or normal liver histology, we selected five matched individuals from each condition for a preliminary pilot HDL proteome analysis. HDL particles were enriched using size-exclusion chromatography, and the proteome of the resulting fraction was analyzed by liquid chromatography tandem mass spectrometry. Differences in the proteomes between the three conditions (normal, SS, NASH) were assessed using label-free quantitative analysis. Gene ontology term analysis was performed to assess the potential impact of proteomic changes on specific functions of HDL particles. Results Of the 95 proteins identified, 12 proteins showed nominally significant differences between the three conditions. Gene ontology term analysis revealed that severity of the liver pathology may significantly impact the anti-thrombotic functions of HDL particles, as suggested by changes in the abundance of HDL-associated proteins such as antithrombin III and plasminogen. Conclusions The pilot data from this study suggest that changes in the HDL proteome may impact the functionality of HDL particles in NAFLD and NASH patients. These proteome changes may alter cardio-protective properties of HDL, potentially contributing to the increased cardiovascular disease risk in affected individuals. Further validation of these protein changes by orthogonal approaches is key to confirming the role of alterations in the HDL proteome in NAFLD and NASH. This will help elucidate the mechanistic effects of the altered HDL proteome on cardioprotective properties of HDL particles. Electronic supplementary material The online version of this article (10.1186/s12014-018-9186-0) contains supplementary material, which is available to authorized users.
- Subjects :
- Proteomics
0301 basic medicine
medicine.medical_specialty
Clinical Biochemistry
lcsh:Medicine
Disease
03 medical and health sciences
chemistry.chemical_compound
High-density lipoprotein
Internal medicine
Diabetes mellitus
medicine
Obesity
High-density lipoproteins
Molecular Biology
business.industry
Research
lcsh:R
Fatty liver
nutritional and metabolic diseases
General Medicine
medicine.disease
Anti-thrombotic
030104 developmental biology
Endocrinology
chemistry
Proteome
Molecular Medicine
lipids (amino acids, peptides, and proteins)
sense organs
Steatohepatitis
business
Non-alcoholic fatty liver disease
Lipoprotein
Subjects
Details
- ISSN :
- 15590275 and 15426416
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Clinical Proteomics
- Accession number :
- edsair.doi.dedup.....f5bde704c61b70b6e0d3b96d6e44c4cb
- Full Text :
- https://doi.org/10.1186/s12014-018-9186-0