Endogenous leptin receptor signaling in the medial nucleus tractus solitarius affects meal size and potentiates intestinal satiation signals.
Leptin receptor (LepRb) signaling in the hindbrain is required for energy balance control. Yet the specific hindbrain neurons and the behavioral processes mediating energy balance control by hindbrain leptin signaling are unknown. Studies here employ genetic [adeno-associated virally mediated RNA interference (AAV-RNAi)] and pharmacological methodologies to specify the neurons and the mechanisms through which hindbrain LepRb signaling contributes to the control of food intake. Results show that AAV-RNAi-mediated LepRb knockdown targeting a region encompassing the mNTS and area postrema (AP) (mNTS/AP LepRbKD) increases overall cumulative food intake by increasing the size of spontaneous meals. Other results show that pharmacological hindbrain leptin delivery and RNAi-mediated mNTS/AP LepRb knockdown increased and decreased the intake-suppressive effects of intraduodenal nutrient infusion, respectively. These meal size and intestinally derived signal amplification effects are likely mediated by LepRb signaling in the mNTS and not the AP, since 4th icv and mNTS parenchymal leptin (0.5 μg) administration reduced food intake, whereas this dose did not influence food intake when injected into the AP. Overall, these findings deepen the understanding of the distributed neuronal systems and behavioral mechanisms that mediate the effects of leptin receptor signaling on the control of food intake.
Dept. of Psychology, School of Arts and Sciences, Univ. of Pennsylvania, 3720 Walnut St., Philadelphia, PA 19104, USA.
Scott E
SE
Kanoski
Shiru
S
Zhao
Douglas J
DJ
Guarnieri
Ralph J
RJ
DiLeone
Jianqun
J
Yan
Bart C
BC
De Jonghe
Kendra K
KK
Bence
Matthew R
MR
Hayes
Harvey J
HJ
Grill
D000818:Animals; D031608:Area Postrema / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D007422:Intestines / Q000187:drug effects / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology; D008297:Male; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000235:genetics / Q000502:physiology*; D012527:Satiation / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*
D020738:Leptin; D054411:Receptors, Leptin