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  • Mouse Liver Compensates Loss of Sgpl1 by Secretion of Sphingolipids into Blood and Bile.

Mouse Liver Compensates Loss of Sgpl1 by Secretion of Sphingolipids into Blood and Bile.

International journal of molecular sciences (2021-10-14)
Anna Katharina Spohner, Katja Jakobi, Sandra Trautmann, Dominique Thomas, Fabian Schumacher, Burkhard Kleuser, Dieter Lütjohann, Khadija El-Hindi, Sabine Grösch, Josef Pfeilschifter, Julie D Saba, Dagmar Meyer Zu Heringdorf
ABSTRACT

Sphingosine 1 phosphate (S1P) lyase (Sgpl1) catalyses the irreversible cleavage of S1P and thereby the last step of sphingolipid degradation. Loss of Sgpl1 in humans and mice leads to accumulation of sphingolipids and multiple organ injuries. Here, we addressed the role of hepatocyte Sgpl1 for regulation of sphingolipid homoeostasis by generating mice with hepatocyte-specific deletion of Sgpl1 (Sgpl1HepKO mice). Sgpl1HepKO mice had normal body weight, liver weight, liver structure and liver enzymes both at the age of 8 weeks and 8 months. S1P, sphingosine and ceramides, but not glucosylceramides or sphingomyelin, were elevated by ~1.5-2-fold in liver, and this phenotype did not progress with age. Several ceramides were elevated in plasma, while plasma S1P was normal. Interestingly, S1P and glucosylceramides, but not ceramides, were elevated in bile of Sgpl1HepKO mice. Furthermore, liver cholesterol was elevated, while LDL cholesterol decreased in 8-month-old mice. In agreement, the LDL receptor was upregulated, suggesting enhanced uptake of LDL cholesterol. Expression of peroxisome proliferator-activated receptor-γ, liver X receptor and fatty acid synthase was unaltered. These data show that mouse hepatocytes largely compensate the loss of Sgpl1 by secretion of accumulating sphingolipids in a specific manner into blood and bile, so that they can be excreted or degraded elsewhere.

MATERIALS
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Product Description

Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid
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Sigma-Aldrich
Collagenase from Clostridium histolyticum, Type IA, 0.5-5.0 FALGPA units/mg solid, ≥125 CDU/mg solid, For general use
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SKUPack SizeAvailabilityPriceQuantity
5 mL
1 Available to ship on January 09, 2025
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$272.00
10 mL
1 Available to ship on January 09, 2025
Details...
$458.00
$320.60
25 mL
1 Available to ship on January 09, 2025
Details...
$901.00
$792.88