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J Clin Med. 2019 Jul 4;8(7). pii: E971. doi: 10.3390/jcm8070971.

The Lipid Status in Patients with Ulcerative Colitis: Sphingolipids are Disease-Dependent Regulated.

Author information

1
Institute of Clinical Pharmacology, Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
2
First Department of Internal Medicine, Division of Gastroenterology, Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
3
Institute for Biostatistics and Mathematical Modelling, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
4
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Branch for Translational Medicine and Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany.
5
Institute of Clinical Pharmacology, Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany. groesch@em.uni-frankfurt.de.

Abstract

The factors that contribute to the development of ulcerative colitis (UC), are still not fully identified. Disruption of the colon barrier is one of the first events leading to invasion of bacteria and activation of the immune system. The colon barrier is strongly influenced by sphingolipids. Sphingolipids impact cell-cell contacts and function as second messengers. We collected blood and colon tissue samples from UC patients and healthy controls and investigated the sphingolipids and other lipids by LC-MS/MS or LC-QTOFMS. The expression of enzymes of the sphingolipid pathway were determined by RT-PCR and immunohistochemistry. In inflamed colon tissue, the de novo-synthesis of sphingolipids is reduced, whereas lactosylceramides are increased. Reduction of dihydroceramides was due to posttranslational inhibition rather than altered serine palmitoyl transferase or ceramide synthase expression in inflamed colon tissue. Furthermore, in human plasma from UC-patients, several sphinglipids change significantly in comparison to healthy controls. Beside sphingolipids free fatty acids, lysophosphatidylcholines and triglycerides changed significantly in the blood of colitis patients dependent on the disease severity. Our data indicate that detraction of the sphingolipid de novo synthesis in colon tissue might be an important trigger for UC. Several lipids changed significantly in the blood, which might be used as biomarkers for disease control; however, diet-related variabilities need to be considered.

KEYWORDS:

DHA; EPA; LC–MS/MS; S1P; ceramide; patient; sphingolipid; ulcerative colitis

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