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Arylhydrocarbon receptor-dependent mIndy (Slc13a5) induction as possible contributor to benzo[a]pyrene-induced lipid accumulation in hepatocytes

Title data

Neuschäfer-Rube, Frank ; Schraplau, Anne ; Schewe, Bettina ; Lieske, Stefanie ; Krützfeldt, Julia-Mignon ; Ringel, Sebastian ; Henkel, Janin ; Birkenfeld, Andreas L. ; Püschel, Gerhard P.:
Arylhydrocarbon receptor-dependent mIndy (Slc13a5) induction as possible contributor to benzo[a]pyrene-induced lipid accumulation in hepatocytes.
In: Toxicology. Vol. 337 (4 November 2015) . - pp. 1-9.
ISSN 1879-3185
DOI: https://doi.org/10.1016/j.tox.2015.08.007

Abstract in another language

Non-alcoholic fatty liver disease is a growing problem in industrialized and developing countries. Hepatic lipid accumulation is the result of an imbalance between fatty acid uptake, fatty acid de novo synthesis, β-oxidation and secretion of triglyceride-rich lipoproteins from the hepatocyte. A central regulator of hepatic lipid metabolism is cytosolic citrate that can either be derived from the mitochondrium or be taken up from the blood via the plasma membrane sodium citrate transporter NaCT, the product of the mammalian INDY gene (SLC13A5). mINDY ablation protects against diet-induced steatosis whereas mINDY expression is increased in patients with hepatic steatosis. Diet-induced hepatic steatosis is also enhanced by activation of the arylhyrocarbon receptor (AhR) both in humans and animal models. Therefore, the hypothesis was tested whether the mINDY gene might be a target of the AhR. In accordance with such a hypothesis, the AhR activator benzo[a]pyrene induced the mINDY expression in primary cultures of rat hepatocytes in an AhR-dependent manner. This induction resulted in an increased citrate uptake and citrate incorporation into lipids which probably was further enhanced by the benzo[a]pyrene-dependent induction of key enzymes of fatty acid synthesis. A potential AhR binding site was identified in the mINDY promoter that appears to be conserved in the human promoter. Elimination or mutation of this site largely abolished the activation of the mINDY promoter by benzo[a]pyrene. This study thus identified the mINDY as an AhR target gene. AhR-dependent induction of the mINDY gene might contribute to the development of hepatic steatosis.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: NAFLD; Non-alcoholic fatty liver disease; SLC13A5
Institutions of the University: Faculties > Faculty of Life Sciences: Food, Nutrition and Health
Result of work at the UBT: No
DDC Subjects: 500 Science
500 Science > 570 Life sciences, biology
Date Deposited: 26 Apr 2021 11:58
Last Modified: 26 Apr 2021 13:02
URI: https://eref.uni-bayreuth.de/id/eprint/64436