title: High pancreatic n-3 fatty acids prevent STZ-induced diabetes in fat-1 mice: inflammatory pathway inhibition.
abstract: OBJECTIVE
  Because of confounding factors, the effects of dietary n-3 polyunsaturated fatty acids (PUFA) on type 1 diabetes remain to be clarified. We therefore evaluated whether fat-1 transgenic mice, a well-controlled experimental model endogenously synthesizing n-3 PUFA, were protected against streptozotocin (STZ)-induced diabetes. We then aimed to elucidate the in vivo response at the pancreatic level.
  
  
  METHODS
  β-Cell destruction was produced by multiple low-doses STZ (MLD-STZ). Blood glucose level, plasma insulin level, and plasma lipid analysis were then performed. Pancreatic mRNA expression of cytokines, the monocyte chemoattractant protein, and GLUT2 were evaluated as well as pancreas nuclear factor (NF)-κB p65 and inhibitor of κB (IκB) protein expression. Insulin and cleaved caspase-3 immunostaining and lipidomic analysis were performed in the pancreas.
  
  
  RESULTS
  STZ-induced fat-1 mice did not develop hyperglycemia compared with wild-type mice, and β-cell destruction was prevented as evidenced by lack of histological pancreatic damage or reduced insulin level. The prevention of β-cell destruction was associated with no proinflammatory cytokine induction (tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase) in the pancreas, a decreased NF-κB, and increased IκB pancreatic protein expression. In the fat-1-treated mice, proinflammatory arachidonic-derived mediators as prostaglandin E₂ and 12-hydroxyeicosatetraenoic acid were decreased and the anti-inflammatory lipoxin A₄ was detected. Moreover, the 18-hydroxyeicosapentaenoic acid, precursor of the anti-inflammatory resolvin E1, was highly increased.
  
  
  CONCLUSIONS
  Collectively, these findings indicate that fat-1 mice were protected against MLD-STZ-induced diabetes and pointed out for the first time in vivo the beneficial effects of n-3 PUFA at the pancreatic level, on each step of the development of the pathology-inflammation, β-cell damage-through cytokine response and lipid mediator production.
authors.affiliation: Université de Bourgogne, UFR Sciences de la Vie, de la Terre et de l'Environnement, Dijon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bellenger
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bellenger
authors.forename: Amandine
authors.initials: A
authors.lastname: Bataille
authors.forename: Karen A
authors.initials: KA
authors.lastname: Massey
authors.forename: Anna
authors.initials: A
authors.lastname: Nicolaou
authors.forename: Mickaël
authors.initials: M
authors.lastname: Rialland
authors.forename: Christian
authors.initials: C
authors.lastname: Tessier
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
authors.forename: Michel
authors.initials: M
authors.lastname: Narce
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D029742:Caenorhabditis elegans Proteins; D015525:Fatty Acids, Omega-3; D007328:Insulin; D008055:Lipids; D051996:Transcription Factor RelA; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases