Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lindquist, C; Bjørndal, B; Rossmann, CR; Tusubira, D; Svardal, A; Røsland, GV; Tronstad, KJ; Hallström, S; Berge, RK.
Increased hepatic mitochondrial FA oxidation reduces plasma and liver TG levels and is associated with regulation of UCPs and APOC-III in rats.
J Lipid Res. 2017; 58(7):1362-1373
Doi: 10.1194/jlr.M074849
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- Co-Autor*innen der Med Uni Graz
- Hallström Seth
- Rossmann Christine Renate
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- Abstract:
- Hepatic mitochondrial function, APOC-III, and LPL are potential targets for triglyceride (TG)-lowering drugs. After 3 weeks of dietary treatment with the compound 2-(tridec-12-yn-1-ylthio)acetic acid (1-triple TTA), the hepatic mitochondrial FA oxidation increased more than 5-fold in male Wistar rats. Gene expression analysis in liver showed significant downregulation of APOC-III and upregulation of LPL and the VLDL receptor. This led to lower hepatic (53%) and plasma (73%) TG levels. Concomitantly, liver-specific biomarkers related to mitochondrial biogenesis and function (mitochondrial DNA, citrate synthase activity, and cytochrome c and TFAM gene expression) were elevated. Interestingly, 1-triple TTA lowered plasma acetylcarnitine levels, whereas the concentration of β-hydroxybutyrate was increased. The hepatic energy state was reduced in 1-triple TTA-treated rats, as reflected by increased AMP/ATP and decreased ATP/ADP ratios, whereas the energy state remained unchanged in muscle and heart. The 1-triple TTA administration induced gene expression of uncoupling protein (UCP)2 and UCP3 in liver. In conclusion, the 1-triple TTA-mediated clearance of blood TG may result from lowered APOC-III production, increased hepatic LPL gene expression, mitochondrial FA oxidation, and (re)uptake of VLDL facilitating drainage of FAs to the liver for β-oxidation and production of ketone bodies as extrahepatic fuel. The possibility that UCP2 and UCP3 mediate a moderate degree of mitochondrial uncoupling should be considered. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetic Acid - chemistry
- Acetic Acid - pharmacology
- Acetylcarnitine - metabolism
- Animals -
- Apolipoprotein C-III - metabolism
- Carnitine - metabolism
- Energy Metabolism - drug effects
- Fatty Acids - metabolism
- Liver - drug effects
- Liver - metabolism
- Male -
- Mitochondria, Liver - drug effects
- Mitochondria, Liver - metabolism
- Mitochondrial Uncoupling Proteins - metabolism
- Oxidation-Reduction -
- Rats -
- Rats, Wistar -
- Triglycerides - blood
- Triglycerides - metabolism
- Find related publications in this database (Keywords)
- 2-(tridec-12-yn-1-ylthio)acetic acid
- lipids
- lipoproteins
- metabolic syndrome
- mitochondria
- nonalcoholic fatty liver disease
- fatty acid metabolism
- lipids/oxidation
- fatty acid
- triglyceride
- uncoupling protein
- apolipoprotein C-III