Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding.
The lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these LHA LepRb neurons innervate the VTA, and leptin action on these neurons restores VTA expression of the rate-limiting enzyme in DA production along with mesolimbic DA content in leptin-deficient animals. Thus, these findings reveal that LHA LepRb neurons link anorexic leptin action to the mesolimbic DA system.
Leinninger
Gina M
GM
Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Jo
Young-Hwan
YH
Leshan
Rebecca L
RL
Louis
Gwendolyn W
GW
Yang
Hongyan
H
Barrera
Jason G
JG
Wilson
Hilary
H
Opland
Darren M
DM
Faouzi
Miro A
MA
Gong
Yusong
Y
Jones
Justin C
JC
Rhodes
Christopher J
CJ
Chua
Streamson
S
Diano
Sabrina
S
Horvath
Tamas L
TL
Seeley
Randy J
RJ
Becker
Jill B
JB
Münzberg
Heike
H
Myers
Martin G
MG
D000818:Animals; D001835:Body Weight; D004298:Dopamine / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D055879:Gene Knock-In Techniques; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000378:metabolism*; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000166:cytology
D020738:Leptin; D054411:Receptors, Leptin; D004298:Dopamine