title: Comparative plasma lipidome between human and cynomolgus monkey: are plasma polar lipids good biomarkers for diabetic monkeys?
abstract: BACKGROUND
  Non-human primates (NHP) are now being considered as models for investigating human metabolic diseases including diabetes. Analyses of cholesterol and triglycerides in plasma derived from NHPs can easily be achieved using methods employed in humans. Information pertaining to other lipid species in monkey plasma, however, is lacking and requires comprehensive experimental analysis.
  
  
  RESULTS
  We examined the plasma lipidome from 16 cynomolgus monkey, Macaca fascicularis, using liquid chromatography coupled with mass spectrometry (LC/MS). We established novel analytical approaches, which are based on a simple gradient elution, to quantify polar lipids in plasma including (i) glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG; phosphatidylserine, PS; phosphatidic acid, PA); (ii) sphingolipids (sphingomyelin, SM; ceramide, Cer; Glucocyl-ceramide, GluCer; ganglioside mannoside 3, GM3). Lipidomic analysis had revealed that the plasma of human and cynomolgus monkey were of similar compositions, with PC, SM, PE, LPC and PI constituting the major polar lipid species present. Human plasma contained significantly higher levels of plasmalogen PE species (p<0.005) and plasmalogen PC species (p<0.0005), while cynomolgus monkey had higher levels of polyunsaturated fatty acyls (PUFA) in PC, PE, PS and PI. Notably, cynomolgus monkey had significantly lower levels of glycosphingolipids, including GluCer (p<0.0005) and GM(3) (p<0.0005), but higher level of Cer (p<0.0005) in plasma than human. We next investigated the biochemical alterations in blood lipids of 8 naturally occurring diabetic cynomolgus monkeys when compared with 8 healthy controls.
  
  
  CONCLUSIONS
  For the first time, we demonstrated that the plasma of human and cynomolgus monkey were of similar compositions, but contained different mol distribution of individual molecular species. Diabetic monkeys exhibited decreased levels of sphingolipids, which are microdomain-associated lipids and are thought to be associated with insulin sensitivity. Significant increases in PG species, which are precursors for cardiolipin biosynthesis in mitochondria, were found in fasted diabetic monkeys (n = 8).
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. bchsgh@nus.edu.sg
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Jeffrey William
authors.initials: JW
authors.lastname: Stebbins
authors.forename: Buu Duyen
authors.initials: BD
authors.lastname: Lam
authors.forename: Wei Fun
authors.initials: WF
authors.lastname: Cheong
authors.forename: Sin Man
authors.initials: SM
authors.lastname: Lam
authors.forename: Francine
authors.initials: F
authors.lastname: Gregoire
authors.forename: Jun
authors.initials: J
authors.lastname: Kusonoki
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood*; D005215:Fasting / Q000097:blood; D005247:Feeding Behavior / Q000502:physiology; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000737:chemistry; D008252:Macaca fascicularis / Q000097:blood*; D010715:Phosphatidylglycerols / Q000097:blood; D010955:Plasmalogens / Q000097:blood; D013107:Sphingolipids / Q000097:blood
chemical_list: D015415:Biomarkers; D008055:Lipids; D010715:Phosphatidylglycerols; D010955:Plasmalogens; D013107:Sphingolipids