Back to Search
Start Over
Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD
- Source :
- Journal of Immunology Research, Journal of Immunology Research, Vol 2021 (2021)
- Publication Year :
- 2021
- Publisher :
- Hindawi Limited, 2021.
-
Abstract
- We performed a panoramic analysis on both human nonalcoholic steatohepatitis (NASH) microarray data and microarray/RNA-seq data from various mouse models of nonalcoholic fatty liver disease NASH/NAFLD with total 4249 genes examined and made the following findings: (i) human NASH and NAFLD mouse models upregulate both cytokines and chemokines; (ii) pathway analysis indicated that human NASH can be classified into metabolic and immune NASH; methionine- and choline-deficient (MCD)+high-fat diet (HFD), glycine N-methyltransferase deficient (GNMT-KO), methionine adenosyltransferase 1A deficient (MAT1A-KO), and HFCD (high-fat-cholesterol diet) can be classified into inflammatory, SAM accumulation, cholesterol/mevalonate, and LXR/RXR-fatty acid β-oxidation NAFLD, respectively; (iii) canonical and noncanonical inflammasomes play differential roles in the pathogenesis of NASH/NAFLD; (iv) trained immunity (TI) enzymes are significantly upregulated in NASH/NAFLD; HFCD upregulates TI enzymes more than cytokines, chemokines, and inflammasome regulators; (v) the MCD+HFD is a model with the upregulation of proinflammatory cytokines and canonical and noncanonical inflammasomes; however, the HFCD is a model with upregulation of TI enzymes and lipid peroxidation enzymes; and (vi) caspase-11 and caspase-1 act as upstream master regulators, which partially upregulate the expressions of cytokines, chemokines, canonical and noncanonical inflammasome pathway regulators, TI enzymes, and lipid peroxidation enzymes. Our findings provide novel insights on the synergies between hyperlipidemia and hypomethylation in establishing TI and promoting inflammation in NASH and NAFLD progression and novel targets for future therapeutic interventions for NASH and NAFLD, metabolic diseases, transplantation, and cancers.
- Subjects :
- Article Subject
Immunology
Hyperlipidemias
Inflammation
Glycine N-Methyltransferase
Diet, High-Fat
Methylation
digestive system
Proinflammatory cytokine
Mice
Immune system
Downregulation and upregulation
Non-alcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease
medicine
Animals
Humans
Immunology and Allergy
Liver X receptor
Mice, Knockout
business.industry
Caspase 1
Immunity
nutritional and metabolic diseases
Inflammasome
Methionine Adenosyltransferase
General Medicine
RC581-607
medicine.disease
digestive system diseases
Transplantation
Disease Models, Animal
Caspases
Cancer research
Cytokines
Immunologic diseases. Allergy
Inflammation Mediators
medicine.symptom
business
Research Article
medicine.drug
Subjects
Details
- ISSN :
- 23147156 and 23148861
- Volume :
- 2021
- Database :
- OpenAIRE
- Journal :
- Journal of Immunology Research
- Accession number :
- edsair.doi.dedup.....1c3fa0c8a479d10c354d6d5d950fe7ef