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Ceramides are associated with inflammatory processes in human mediastinal adipose tissue
Institution:1. Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden;2. Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden;3. Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden;4. Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 – Anexo – CEP, 90035-003 Porto Alegre, RS, Brazil;2. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350 – CEP, 90035-003 Porto Alegre, RS, Brazil;1. Division of Oral Ecology and Biochemistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan;2. Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan;3. Department of Thoracic Surgery, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-8575, Japan;4. Division of Preventive Dentistry, Tohoku University Hospital, Sendai 980-8575, Japan;3. From the Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston South Carolina 29425;4. Departments of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston South Carolina 29425;6. Department of Public Health, Medical University of South Carolina, Charleston South Carolina 29425;5. the Department of Molecular Biology and Genetics, 34662 Istanbul, Turkey;1. Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children''s Hospital, Capital Medical University, 100045 Beijing, China;2. Department of Pediatrics and the Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, USA
Abstract:Background and AimCeramides are poorly characterized in human adipose tissue. The aim of this study was to investigate concentrations of different ceramide species in human subcutaneous and visceral adipose tissue depots and to determine associations between ceramides and global gene expression profiles.Methods and ResultsConcentrations of six ceramide species were determined in plasma and in subcutaneous and mediastinal adipose tissue from 10 overweight subjects (BMI 29.4 ± 4.9 kg/m2). In the adipose tissue biopsies gene expression arrays were performed and relationships between ceramides and gene expression analyzed. Immunostaining of the two adipose tissue depots was performed in an independent group of 10 patients. Mediastinal adipose tissue contained significantly higher concentrations (p < 0.05) of all six ceramide species than the subcutaneous depot. Of the six ceramides in plasma, concentrations of only two (Cer d18:1/18:0 and Cer d18:1/22:0) correlated significantly (p < 0.05) with the corresponding species in mediastinal adipose tissue, but there were no significant correlations between ceramides in plasma and subcutaneous adipose tissue. Multivariate analysis identified significant correlations between the total ceramide concentration and global gene expression within mediastinal, but not subcutaneous adipose tissue, according to cross-validation. Gene ontology analysis of genes related to ceramides in the mediastinal depot revealed that genes positively correlated with ceramides were associated mainly with immune and inflammatory categories, while genes negatively correlated with ceramides were associated mainly with lipid and carbohydrate metabolism.ConclusionsCeramides in human mediastinal adipose tissue may be involved in inflammation and lipid and carbohydrate metabolism.
Keywords:Adipose tissue  Ceramide  Inflammation  ACER1-3"}  {"#name":"keyword"  "$":{"id":"kwrd0030"}  "$$":[{"#name":"text"  "_":"alkaline ceramidase 1-3  ASAH1-2"}  {"#name":"keyword"  "$":{"id":"kwrd0040"}  "$$":[{"#name":"text"  "_":"neutral ceramidase 1-2  BMI"}  {"#name":"keyword"  "$":{"id":"kwrd0050"}  "$$":[{"#name":"text"  "_":"body mass index  CAD"}  {"#name":"keyword"  "$":{"id":"kwrd0060"}  "$$":[{"#name":"text"  "_":"coronary artery disease  CERK"}  {"#name":"keyword"  "$":{"id":"kwrd0070"}  "$$":[{"#name":"text"  "_":"ceramide kinase  CRP"}  {"#name":"keyword"  "$":{"id":"kwrd0080"}  "$$":[{"#name":"text"  "_":"C-reactive protein  DABG"}  {"#name":"keyword"  "$":{"id":"kwrd0090"}  "$$":[{"#name":"text"  "_":"distance above background  DEGS1-2"}  {"#name":"keyword"  "$":{"id":"kwrd0100"}  "$$":[{"#name":"text"  "_":"dihydroceramide desaturase 1-2  GLUT4"}  {"#name":"keyword"  "$":{"id":"kwrd0110"}  "$$":[{"#name":"text"  "_":"glucose transporter 4  GM3"}  {"#name":"keyword"  "$":{"id":"kwrd0120"}  "$$":[{"#name":"text"  "_":"monosialodihexosylganglioside  GO"}  {"#name":"keyword"  "$":{"id":"kwrd0130"}  "$$":[{"#name":"text"  "_":"gene ontology  HbA1c"}  {"#name":"keyword"  "$":{"id":"kwrd0140"}  "$$":[{"#name":"text"  "_":"glycosylated hemoglobin  HDL"}  {"#name":"keyword"  "$":{"id":"kwrd0150"}  "$$":[{"#name":"text"  "_":"high density lipoprotein  LASS1-6"}  {"#name":"keyword"  "$":{"id":"kwrd0160"}  "$$":[{"#name":"text"  "_":"ceramide synthase 1-6  LDL"}  {"#name":"keyword"  "$":{"id":"kwrd0170"}  "$$":[{"#name":"text"  "_":"low density lipoprotein  OPLS"}  {"#name":"keyword"  "$":{"id":"kwrd0180"}  "$$":[{"#name":"text"  "_":"orthogonal partial least squares  PLS"}  {"#name":"keyword"  "$":{"id":"kwrd0190"}  "$$":[{"#name":"text"  "_":"partial least squares  PPARγ"}  {"#name":"keyword"  "$":{"id":"kwrd0200"}  "$$":[{"#name":"text"  "_":"peroxisome proliferator-activator receptor γ  RIN"}  {"#name":"keyword"  "$":{"id":"kwrd0210"}  "$$":[{"#name":"text"  "_":"RNA integrity number  RMA"}  {"#name":"keyword"  "$":{"id":"kwrd0220"}  "$$":[{"#name":"text"  "_":"robust multiple-array average  S1P"}  {"#name":"keyword"  "$":{"id":"kwrd0230"}  "$$":[{"#name":"text"  "_":"sphingosine-1-phosphate  SD"}  {"#name":"keyword"  "$":{"id":"kwrd0240"}  "$$":[{"#name":"text"  "_":"standard deviation  SGMS1-2"}  {"#name":"keyword"  "$":{"id":"kwrd0250"}  "$$":[{"#name":"text"  "_":"phosphatidylcholine:ceramide cholinephosphotransferase 1-2  SMPD1-4"}  {"#name":"keyword"  "$":{"id":"kwrd0260"}  "$$":[{"#name":"text"  "_":"sphingomyelinase 1-4  SPHK1-2"}  {"#name":"keyword"  "$":{"id":"kwrd0270"}  "$$":[{"#name":"text"  "_":"sphingosine kinase 1-2  SPTLC1-3"}  {"#name":"keyword"  "$":{"id":"kwrd0280"}  "$$":[{"#name":"text"  "_":"serine palmitoyltransferase  long chain base subunit 1-3  ST3GAL5"}  {"#name":"keyword"  "$":{"id":"kwrd0290"}  "$$":[{"#name":"text"  "_":"GM3 synthase  UGCG"}  {"#name":"keyword"  "$":{"id":"kwrd0300"}  "$$":[{"#name":"text"  "_":"UDP-glucose ceramide glucosyltransferase  UGT8"}  {"#name":"keyword"  "$":{"id":"kwrd0310"}  "$$":[{"#name":"text"  "_":"UDP glycosyltransferase 8
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