title: Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  The direct role of leptin in vascular disease remains controversial. The objective of this study was to examine the effects of leptin treatment on atherosclerosis and thrombosis in atherosclerotic-prone mice.
  
  
  RESULTS
  Sixteen-week-old, male apolipoprotein E-deficient mice were treated with injections of recombinant leptin (125 microg per day IP; n=10) or vehicle (n=10) for 4 weeks. Leptin treatment resulted in reduced epididymal fat (352+/-30.7 versus 621+/-61.5 mg; P=0.005) and fasting insulin (0.57+/-0.25 versus 1.7+/-0.22 ng/mL; P=0.014). Despite these metabolic benefits, leptin treatment resulted in an increase in atherosclerosis (8.0+/-0.95% versus 5.4+/-0.59% lesion surface coverage; P<0.05). Leptin treatment also resulted in a shortened time to occlusive thrombosis after vascular injury (21+/-2.1 versus 34.6+/-5.4 minutes; P=0.045).
  
  
  CONCLUSIONS
  These studies indicate that exogenous leptin promotes atherosclerosis and thrombosis and support the concept that elevations of leptin may increase the risk for cardiovascular disease.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, niversity of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Bodary
authors.forename: Shufang
authors.initials: S
authors.lastname: Gu
authors.forename: Yuechun
authors.initials: Y
authors.lastname: Shen
authors.forename: Alyssa H
authors.initials: AH
authors.lastname: Hasty
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Buckler
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Eitzman
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood; D005215:Fasting; D005456:Fluorescent Dyes; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012395:Rose Bengal; D013927:Thrombosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D005456:Fluorescent Dyes; D007328:Insulin; D020738:Leptin; D011994:Recombinant Proteins; D014280:Triglycerides; D012395:Rose Bengal; D002784:Cholesterol