Rein-Fischboeck, Lisa and Haberl, Elisabeth M. and Pohl, Rebekka and Schmid, Verena and Feder, Susanne and Krautbauer, Sabrina and Liebisch, Gerhard and Buechler, Christa (2018) Alpha-syntrophin null mice are protected from non-alcoholic steatohepatitis in the methionine-choline-deficient diet model but not the atherogenic diet model. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1863 (5). pp. 526-537. ISSN 1388-1981, 0006-3002
Full text not available from this repository. (Request a copy)Abstract
Adipose tissue dysfunction contributes to the pathogenesis of non-alcoholic steatohepatitis (NASH). The adapter protein alpha-syntrophin (SNTA) is expressed in adipocytes. Knock-down of SNTA increases preadipocyte proliferation and formation of small lipid droplets, which are both characteristics of healthy adipose tissue. To elucidate a potential protective role of SNTA in NASH, SNTA null mice were fed a methionine-choline-deficient (MCD) diet or an atherogenic diet which are widely used as preclinical NASH models. MCD diet mediated loss of fat mass was largely improved in SNTA-/- mice compared to the respective wild type animals. Hepatic lipids were mostly unchanged while the oxidative stress marker malondialdehyde was only induced in the wild type mice. The expression of inflammatory markers and macrophage immigration into the liver were reduced in SNTA-/- animals. This protective function of SNTA loss was absent in atherogenic diet induced NASH. Here, hepatic expression of inflammatory and fibrotic genes was similar in both genotypes though mutant mice gained less body fat during feeding. Hepatic cholesterol and ceramide were strongly induced in both strains upon feeding the atherogenic diet, while hepatic sphingomyelin, phosphatidylserine and phosphatidylethanolamine levels were suppressed. SNTA deficient mice are protected from fat loss and NASH in the experimental MCD model. NASH induced by an atherogenic diet is not influenced by loss of SNTA. The present study suggests the use of different experimental NASH models to study the pathophysiological role of proteins like SNTA in NASH.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TANDEM MASS-SPECTROMETRY; FATTY LIVER-DISEASE; HIGH-THROUGHPUT QUANTIFICATION; CANCER-ASSOCIATED CACHEXIA; HEPATOCELLULAR-CARCINOMA; INSULIN-RESISTANCE; LIPID EXTRACTION; OBESE MICE; ESI-MS/MS; CERAMIDE; Ceramide; Cholesterol; Inflammation; Lipase; Adipocytes |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Feb 2020 13:03 |
| Last Modified: | 19 Feb 2020 13:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14603 |
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