Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Jha, P; Knopf, A; Koefeler, H; Mueller, M; Lackner, C; Hoefler, G; Claudel, T; Trauner, M; .
Role of adipose tissue in methionine-choline-deficient model of non-alcoholic steatohepatitis (NASH).
BBA-MOL BASIS DIS. 2014; 1842(7): 959-970.
Doi: 10.1016/j.bbadis.2014.02.012
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Jha Pooja
- Lackner Karoline
- Trauner Michael
- Co-Autor*innen der Med Uni Graz
- Claudel Thierry
- Höfler Gerald
- Knopf Astrid
- Köfeler Harald
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Methionine-choline-deficient (MCD) diet is a widely used dietary model of non-alcoholic steatohepatitis (NASH) in rodents. However, the contribution of adipose tissue to MCD-induced steatosis, and inflammation as features of NASH are not fully understood. The goal of this study was to elucidate the role of adipose tissue fatty acid (FA) metabolism, adipogenesis, lipolysis, inflammation and subsequent changes in FA profiles in serum and liver in the pathogenesis of steatohepatitis. We therefore fed ob/ob mice with control or MCD diet for 5 weeks. MCD-feeding increased adipose triglyceride lipase and hormone sensitive lipase activities in all adipose depots which may be attributed to increased systemic FGF21 levels. The highest lipase enzyme activity was exhibited by visceral WAT. Non-esterified fatty acid (NEFA)-18:2n6 was the predominantly elevated FA species in serum and liver of MCD-fed ob/ob mice, while overall serum total fatty acid (TFA) composition was reduced. In contrast, an overall increase of all FA species from TFA pool was found in liver, reflecting the combined effects of increased FA flux to liver, decreased FA oxidation and decrease in lipase activity in liver. NAFLD activity score was increased in liver, while WAT showed no changes and BAT showed even reduced inflammation. This study demonstrates a key role for adipose tissue lipases in the pathogenesis of NASH and provides a comprehensive lipidomic profiling of NEFA and TFA homeostasis in serum and liver. Our findings provide novel mechanistic insights for the role of WAT in progression of MCD-induced liver injury. Copyright © 2014. Published by Elsevier B.V.
- Find related publications in this database (using NLM MeSH Indexing)
- Adipogenesis - physiology
- Adipose Tissue - metabolism Adipose Tissue - pathology
- Animals -
- Choline - metabolism
- Disease Models, Animal -
- Fatty Acids - metabolism
- Fatty Acids, Nonesterified - metabolism
- Fatty Liver - metabolism Fatty Liver - pathology
- Fibroblast Growth Factors - metabolism
- Inflammation - metabolism Inflammation - pathology
- Lipase - metabolism
- Lipid Metabolism - physiology
- Lipolysis - physiology
- Liver - metabolism Liver - pathology
- Methionine - deficiency Methionine - metabolism
- Mice -
- Non-alcoholic Fatty Liver Disease -
- Obesity - metabolism Obesity - pathology
- Oxidation-Reduction -
- Find related publications in this database (Keywords)
- NAFLD
- Lipolysis
- Liver
- ATGL
- HSL
- FGF21