title: Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue.
abstract: BACKGROUND
  Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue.
  
  
  METHODS
  Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject.
  
  
  RESULTS
  Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot.
  
  
  CONCLUSIONS
  Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue.
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Kolak
authors.forename: Joanna
authors.initials: J
authors.lastname: Gertow
authors.forename: Jukka
authors.initials: J
authors.lastname: Westerbacka
authors.forename: Scott A
authors.initials: SA
authors.lastname: Summers
authors.forename: Jan
authors.initials: J
authors.lastname: Liska
authors.forename: Anders
authors.initials: A
authors.lastname: Franco-Cereceda
authors.forename: Matej
authors.initials: M
authors.lastname: Orešič
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Fisher
mesh_terms: D017667:Adipocytes / Q000201:enzymology; D000328:Adult; D001055:Apolipoproteins B / Q000378:metabolism; D055572:Ceramidases / Q000235:genetics / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000201:enzymology; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology* / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D051049:Sphingosine N-Acyltransferase / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D000099157:Sphingosine Kinase
chemical_list: D001055:Apolipoproteins B; D055572:Ceramidases; D002518:Ceramides; D017853:Phosphotransferases (Alcohol Group Acceptor); D013108:Sphingomyelin Phosphodiesterase; D051049:Sphingosine N-Acyltransferase; D000099157:Sphingosine Kinase