Wanninger, Josef and Neumeier, Markus and Weigert, Johanna and Liebisch, Gerhard and Weiss, Thomas S. and Schaeffler, Andreas and Aslanidis, Charalampos and Schmitz, Gerd and Schoelmerich, Juergen and Buechler, Christa (2008) Metformin reduces cellular lysophosphatidylcholine and thereby may lower apolipoprotein B secretion in primary human hepatocytes. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1781 (6-7). pp. 321-325. ISSN 1388-1981,
Full text not available from this repository. (Request a copy)Abstract
The biguanide metformin is an oral antihyperglycemic drug for the treatment of type 2 diabetes mellitus. Further, a moderate improvement of dyslipidemia by metformin was reported, and therefore, the effect of metformin on the release of apolipoprotein B (ApoB) and ApoE in primary human hepatocytes was determined. Metformin at 0.5 and 1 mM reduced hepatic ApoB secretion but ApoE was not altered. Metformin is well known to stimulate the AMP kinase that subsequently reduces hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB. However, HNF4-alpha was only diminished by 1 mM metformin and ApoB mRNA was not suppressed indicating that this pathway may not explain reduced ApoB release. Lower abundance of lysophosphatidylcholine (lysoPC) may also diminish ApoB secretion. Therefore, electrospray ionization tandem mass spectrometry was applied to measure cellular lipids. PC, lysoPC (produced by hydrolysis of PC), phosphatidylserine and sphingomyelin (derived from PC) were lower in metformin-treated hepatocytes whereas phosphatidylethanolamine, an alternative precursor of PC, was not affected. In addition, ABCB4, the canalicular membrane flippase essential for biliary PC secretion, was diminished. Supplementation with lysoPC led to a selective elevation of endogenous lysoPC and rescued ApoB secretion in metformin-treated cells. Therefore, it is concluded that metformin reduces lysoPC in human hepatocytes and this may secondarily lead to a therapeutically beneficial lower release of ApoB. (c) 2008 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATED PROTEIN-KINASE; TANDEM MASS-SPECTROMETRY; FATTY LIVER-DISEASE; HIGH-THROUGHPUT QUANTIFICATION; TYPE-2 DIABETES-MELLITUS; PHOSPHATIDYLCHOLINE SYNTHESIS; NONALCOHOLIC STEATOHEPATITIS; RAT HEPATOCYTES; HEPG2 CELLS; METABOLISM; dyslipidemia; apolipoprotein B; metformin; phosphatidylcholine; ABCB4 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Oct 2020 12:01 |
| Last Modified: | 29 Oct 2020 12:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30766 |
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