Leptin, the product of the ob gene, regulates food intake, energy expenditu
re, and other physiological functions of the peripheral tissues. Leptin rec
eptors have been identified in the hypothalamus and in extrahypothalamic ti
ssues. Increased circulating leptin levels have been correlated with cardio
vascular disease, obesity. aging. infection with bacterial lipopolysacchari
de, and high-fat diets. All these conditions have also been correlated with
increased vascular calcification, a hallmark of atherosclerotic and age-re
lated vascular disease. In addition, the differentiation of marrow osteopro
genitor cells is regulated by leptin, Thus, we hypothesized that leptin may
regulate the calcification of vascular cells. In this report, we tested th
e effects of leptin on a previously characterized subpopulation of vascular
cells that undergo osteoblastic differentiation and calcification in vitro
. When treated with leptin, these calcifying vascular cells had a significa
nt 5- to 10-fold increase in alkaline phosphatase activity, a marker of ost
eogenic differentiation of osteoblastic cells. Prolonged treatment with lep
tin enhanced the calcification of these cells, further supporting the pro-o
steogenic differentiation effects of leptin. Furthermore, the presence of t
he leptin receptor on calcifying vascular cells was demonstrated using reve
rse transcriptase polymerase chain reaction, immunocytochemistry and Wester
n blot analysis. We also identified the presence of leptin receptor in the
mouse artery wall, localized to subpopulations of medial and adventitial ce
lls, and the expression of leptin by artery wall cells and atherosclerotic
Lesions in mice. Taken together, these results suggest that leptin regulate
s the osteoblastic differentiation and calcification of vascular cells and
that the artery wall may be an important peripheral tissue target of leptin
action.