Jk. Elmquist et al., DISTRIBUTIONS OF LEPTIN RECEPTOR MESSENGER-RNA ISOFORMS IN THE RAT-BRAIN, Journal of comparative neurology, 395(4), 1998, pp. 535-547
Leptin, secreted by white adipocytes, has profound feeding, metabolic,
and neuroendocrine effects. Leptin acts on the brain, but the specifi
c anatomic sites and pathways responsible for mediating these effects
are still unclear. We have systematically examined distributions of mR
NA of leptin receptor isoforms in the rat brain by using a probe speci
fic for the long form and a probe recognizing all known forms of the l
eptin receptor. The mRNA for the long form of the receptor (OB-Rb) loc
alized to selected nuclear groups in the rat brain. Within the hypotha
lamus, dense hybridization was observed in the arcuate, dorsomedial, v
entromedial, and ventral premamillary nuclei. Within the dorsomedial n
ucleus, particularly intense hybridization was observed in the caudal
regions of the nucleus ventral to the compact formation. Receptors wer
e preferentially localized to the dorsomedial division of the ventrome
dial nucleus. Hybridization accumulated throughout the arcuate nucleus
, extending from the retrochiasmatic region to the posterior periventr
icular region. Moderate hybridization was observed in the periventricu
lar hypothalamic nucleus, lateral hypothalamic area, medial mammillary
nucleus, posterior hypothalamic nucleus, nucleus of the lateral olfac
tory tract, and within substantia nigra pars compacta. Several thalami
c nuclei were also found to contain dense hybridization. These groups
included the mediodorsal, ventral anterior, ventral medial, submedial,
ventral posterior, and lateral dorsal thalamic nuclei; Hybridization
was also observed in the medial and lateral geniculate nuclei. Intense
hybridization was observed in the Purkinje and granular cell layers o
f the cerebellum. A probe recognizing all known forms of the leptin re
ceptor hybridized to all of these sites within the brain. In addition,
intense hybridization was observed in the choroid plexus, meninges, a
nd also surrounding blood vessels. These findings indicate that circul
ating leptin may act through hypothalamic nuclear groups involved in r
egulating feeding, body weight, and neuroendocrine function. The local
ization of leptin receptor mRNA in extrahypothalamic sites in the thal
amus and cerebellum suggests that leptin may act on specific sensory a
nd motor systems. Leptin receptors localized in nonneuronal cells in t
he meninges, choroid plexus, and blood vessels may be involved in tran
sport of leptin into the brain and in the clearance of leptin from the
cerebrospinal fluid. (C) 1998 Wiley-Liss, Inc.