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SHR Neuro Krebs Kardio Lipid

Jaeger, D; Schoiswohl, G; Hofer, P; Schreiber, R; Schweiger, M; Eichmann, TO; Pollak, NM; Poecher, N; Grabner, GF; Zierler, KA; Eder, S; Kolb, D; Radner, FP; Preiss-Landl, K; Lass, A; Zechner, R; Kershaw, EE; Haemmerle, G.
Fasting-induced G0/G1 switch gene 2 and FGF21 expression in the liver are under regulation of adipose tissue derived fatty acids.
J Hepatol. 2015; 63(2):437-445 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Hofer Peter
Kolb Dagmar

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Number of Figures: 5
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Adipose tissue (AT)-derived fatty acids (FAs) are utilized for hepatic triacylglycerol (TG) generation upon fasting. However, their potential impact as signaling molecules is not established. Herein we examined the role of exogenous AT-derived FAs in the regulation of hepatic gene expression by investigating mice with a defect in AT-derived FA supply to the liver. Plasma FA levels, tissue TG hydrolytic activities and lipid content were determined in mice lacking the lipase co-activator comparative gene identification-58 (CGI-58) selectively in AT (CGI-58-ATko) applying standard protocols. Hepatic expression of lipases, FA oxidative genes, transcription factors, ER stress markers, hormones and cytokines were determined by qRT-PCR, Western blotting and ELISA. Impaired AT-derived FA supply upon fasting of CGI-58-ATko mice causes a marked defect in liver PPARα-signaling and nuclear CREBH translocation. This severely reduced the expression of respective target genes such as the ATGL inhibitor G0/G1 switch gene-2 (G0S2) and the endocrine metabolic regulator FGF21. These changes could be reversed by lipid administration and raising plasma FA levels. Impaired AT-lipolysis failed to induce hepatic G0S2 expression in fasted CGI-58-ATko mice leading to enhanced ATGL-mediated TG-breakdown strongly reducing hepatic TG deposition. On high fat diet, impaired AT-lipolysis counteracts hepatic TG accumulation and liver stress linked to improved systemic insulin sensitivity. AT-derived FAs are a critical regulator of hepatic fasting gene expression required for the induction of G0S2-expression in the liver to control hepatic TG-breakdown. Interfering with AT-lipolysis or hepatic G0S2 expression represents an effective strategy for the treatment of hepatic steatosis. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Adipose Tissue - metabolism
Animals -
Blotting, Western -
Diet, High-Fat - adverse effects
Disease Models, Animal -
Enzyme-Linked Immunosorbent Assay -
Fasting - metabolism
Fatty Acids - metabolism
Fatty Liver - genetics
Fatty Liver - metabolism
Fatty Liver - pathology
Fibroblast Growth Factors - biosynthesis
Fibroblast Growth Factors - genetics
Gene Expression Regulation -
Genes, Switch -
Liver - metabolism
Liver - ultrastructure
Mice -
Mice, Transgenic -
Microscopy, Electron -
RNA - genetics
Real-Time Polymerase Chain Reaction -

Find related publications in this database (Keywords)
Hepatic steatosis
G0/G1 switch gene 2
Fibroblast growth factor 21
PPAR alpha
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