Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E-deficient mice.
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.
Bodary
Peter F
PF
Division of Cardiovascular Medicine, Department of Internal Medicine, niversity of Michigan Medical Center, Ann Arbor, MI, USA.
Gu
Shufang
S
Shen
Yuechun
Y
Hasty
Alyssa H
AH
Buckler
Joshua M
JM
Eitzman
Daniel T
DT
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
D001057:Apolipoproteins E; D016207:Cytokines; D005456:Fluorescent Dyes; D007328:Insulin; D020738:Leptin; D011994:Recombinant Proteins; D014280:Triglycerides; D012395:Rose Bengal; D002784:Cholesterol