title: Ceramide Synthase 5 Is Essential to Maintain C16:0-Ceramide Pools and Contributes to the Development of Diet-induced Obesity.
abstract: Ceramides are bioactive sphingolipids, which are composed of sphingoid bases carrying acyl chains of various lengths. Ceramides are synthesized by a family of six ceramide synthases (CerS) in mammals, which produce ceramides with differentN-linked acyl chains. Increased ceramide levels are known to contribute to the development of obesity and insulin resistance. Recently, it has been demonstrated that the ceramide acylation pattern is of particular importance for an organism to maintain energy homeostasis. However, which of theCerSfamily members are involved in this process is not yet completely known. Using newly developedCerS5knock-out mice, we show here thatCerS5is essential to maintain cellular C16:0sphingolipid pools in lung, spleen, muscle, liver, and white adipose tissue. Glycerophospholipid levels inCerS5-deficient mice were not altered. We found a strong impact of CerS5-dependent ceramide synthesis in white adipose tissue after high fat diet feeding. In skeletal muscle, liver, and spleen, C16:0-ceramide levels were altered independent of feeding conditions. The loss ofCerS5is associated with reduced weight gain and improved systemic health, including maintenance of glucose homeostasis and reduced white adipose tissue inflammation after high fat diet challenge. Our findings indicate that reduction of endogenous C16:0-ceramide by genetic inhibition ofCerS5is sufficient to ameliorate obesity and its comorbidities.
authors: From the LIMES-Institute, Program Unit Development, Genetics and Molecular Physiology, Molecular Developmental Biology, University of Bonn, Carl-Troll-Strasse 31 and.
authors: Dominic
authors: D
authors: Gosejacob
authors: From the LIMES-Institute, Program Unit Development, Genetics and Molecular Physiology, Molecular Developmental Biology, University of Bonn, Carl-Troll-Strasse 31 and.
authors: Philipp S
authors: PS
authors: Jäger
authors: IMBIO, Molecular Biotechnology, University of Bonn, Karlrobert-Kreiten-Str. 13, 53115 Bonn, Germany.
authors: Katharina
authors: K
authors: Vom Dorp
authors: From the LIMES-Institute, Program Unit Development, Genetics and Molecular Physiology, Molecular Developmental Biology, University of Bonn, Carl-Troll-Strasse 31 and.
authors: Martin
authors: M
authors: Frejno
authors: From the LIMES-Institute, Program Unit Development, Genetics and Molecular Physiology, Molecular Developmental Biology, University of Bonn, Carl-Troll-Strasse 31 and.
authors: Anne C
authors: AC
authors: Carstensen
authors: From the LIMES-Institute, Program Unit Development, Genetics and Molecular Physiology, Molecular Developmental Biology, University of Bonn, Carl-Troll-Strasse 31 and.
authors: Monika
authors: M
authors: Köhnke
authors: From the LIMES-Institute, Program Unit Development, Genetics and Molecular Physiology, Molecular Developmental Biology, University of Bonn, Carl-Troll-Strasse 31 and.
authors: Joachim
authors: J
authors: Degen
authors: IMBIO, Molecular Biotechnology, University of Bonn, Karlrobert-Kreiten-Str. 13, 53115 Bonn, Germany.
authors: Peter
authors: P
authors: Dörmann
authors: From the LIMES-Institute, Program Unit Development, Genetics and Molecular Physiology, Molecular Developmental Biology, University of Bonn, Carl-Troll-Strasse 31 and m.hoch@uni-bonn.de.
authors: Michael
authors: M
authors: Hoch
mesh_terms: D052436:Adipose Tissue, White / Q000201:enzymology / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002518:Ceramides / Q000096:biosynthesis*; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000009:adverse effects*; D015870:Gene Expression; D005951:Glucose Tolerance Test; D007333:Insulin Resistance / Q000235:genetics; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009765:Obesity / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D051049:Sphingosine N-Acyltransferase / Q000172:deficiency / Q000235:genetics*; D013154:Spleen / Q000201:enzymology / Q000473:pathology
chemical_list: D001786:Blood Glucose; D002518:Ceramides; D004041:Dietary Fats; D007527:Isoenzymes; D051049:Sphingosine N-Acyltransferase
keywords: adipose tissue metabolism; ceramide; ceramide synthase; diabetes; gene knockout; insulin resistance; lipid metabolism; metabolism; obesity; sphingolipid