title: The phospholipase A(2) inhibitor methyl indoxam suppresses diet-induced obesity and glucose intolerance in mice.
abstract: OBJECTIVE
  Previous results have shown that mice lacking in the group 1B phospholipase A(2) (Pla2g1b) are resistant to obesity and diabetes induced by feeding a diabetogenic high-fat/high-carbohydrate diet. This study examined the potential of using the Pla2g1b inhibitor methyl indoxam as therapy to suppress diet-induced obesity and diabetes.
  
  
  METHODS
  Male C57BL/6 mice were fed the diabetogenic diet with or without methyl indoxam supplementation. Body weight gain, fasting plasma glucose levels, glucose tolerance and postprandial lysophospholipid absorption were compared.
  
  
  RESULTS
  Wild-type C57BL/6 mice fed the diabetogenic diet without Pla2g1b inhibitor showed 31 and 69% body weight gain after 4 and 10 weeks respectively. These animals also showed elevated plasma glucose levels and were glucose intolerant. In contrast, C57BL/6 mice fed the diabetogenic diet with 90 mg.kg(-1) of methyl indoxam gained only 5% body weight after 10 weeks. These animals were also euglycaemic and displayed normal glucose excursion rates in glucose tolerance test. Methyl indoxam suppression of diet-induced body weight gain and glucose intolerance was correlated with the inhibition of Pla2g1b-mediated postprandial lysophospholipid absorption.
  
  
  CONCLUSIONS
  These results show that oral supplementation of a diabetogenic diet with the Pla2g1b inhibitor methyl indoxam effectively suppresses diet-induced obesity and diabetes in mice. This suggests that Pla2g1b inhibition may be a potentially effective oral therapeutic option for treatment of obesity and diabetes.
authors: Department of Pathology and Laboratory Medicine, Genome Research Institute, University of Cincinnati College of Medicine, 2120 E. Galbraith Road, Cincinnati, OH 45237-0507, USA. david.hui@uc.edu
authors: D Y
authors: DY
authors: Hui
authors: M J
authors: MJ
authors: Cope
authors: E D
authors: ED
authors: Labonté
authors: H-T
authors: HT
authors: Chang
authors: J
authors: J
authors: Shao
authors: E
authors: E
authors: Goka
authors: A
authors: A
authors: Abousalham
authors: D
authors: D
authors: Charmot
authors: J
authors: J
authors: Buysse
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001646:Bile / Q000187:drug effects / Q000201:enzymology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D018938:Caco-2 Cells; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D054500:Group IB Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology*; D008246:Lysophospholipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D019518:Postprandial Period; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D001713:Biphenyl Compounds; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D007211:Indoles; D008246:Lysophospholipids; D011994:Recombinant Proteins; C546301:methyl indoxam; D054500:Group IB Phospholipases A2