title: Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  The adipocyte fatty acid-binding protein (FABP) aP2 is expressed by adipocytes and macrophages and modulates insulin resistance, glucose and lipid metabolism, and atherosclerosis. Insulin sensitivity is improved in obese but not in lean aP2-deficient mice. A second fatty acid-binding protein, mal1, also is expressed in adipocytes and macrophages, and mal1 deficiency produces similar effects on insulin resistance. We tested the hypothesis that combined aP2 and mal1 deficiency would produce synergistic effects on metabolism and reduce atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice.
  
  
  RESULTS
  Male and female apoE-/- mice null for both aP2 and mal1 (3KO) and apoE-/- controls were fed a low-fat chow diet for 16 or 56 weeks. Lean 3KO mice had significantly lower serum cholesterol and triglycerides as well as improved insulin and glucose tolerance as compared with controls. Analysis of atherosclerotic lesions in the 3KO mice showed dramatic reductions in both early (20 weeks) and late-stage (60 weeks) atherosclerosis. Strikingly, survival in the 3KO mice was improved by 67% as compared with apoE-/- controls when challenged with the Western diet for 1 year.
  
  
  CONCLUSIONS
  Combined aP2 and mal1 deficiency improved glucose and lipid metabolism, reduced atherosclerosis, and improved survival in apoE-/- mice, making these proteins important therapeutic targets for the prevention of the cardiovascular consequences of the metabolic syndrome.
authors.affiliation: Research Department and Geriatric Research, Education, and Clinical Center, VA Tennessee Valley Healthcare System, Nashville, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Boord
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.forename: Liza
authors.initials: L
authors.lastname: Makowski
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Babaev
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
authors.forename: MacRae F
authors.initials: MF
authors.lastname: Linton
authors.forename: Gökhan S
authors.initials: GS
authors.lastname: Hotamisligil
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D018752:Diet, Fat-Restricted; D050556:Fatty Acid-Binding Proteins; D005260:Female; D006938:Hyperlipoproteinemia Type II / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D008136:Longevity / Q000235:genetics; D008297:Male; D008643:Mesentery / Q000473:pathology; D024821:Metabolic Syndrome / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics; D009929:Organ Size; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D014280:Triglycerides; D002784:Cholesterol