Article Figures & Data
Figures
- Figure 1.
MBH leucine and KIC injections reduce food intake and body weight in rat and mouse. a–h , Cumulative (Cum.) food intake ( a , e ), 24 h change in body weight (BW) ( b , f ), mean meal size ( c , g ), and cumulative meal number ( d , h ) in rat ( a–d , n = 10–12) and mouse ( e–h , n = 8) following an MBH injection of aCSF, leucine, or KIC (injection design 1). Data are means ± SEM. *p < 0.05 versus aCSF; **p < 0.01 versus aCSF; ***p < 0.001 versus aCSF.
- Figure 2.
MBH CIC decreases food intake and body weight in mouse. a–d , Food intake ( a ), meal number ( b ), meal size ( c ), and body weight ( d ) in mouse infused for 8 d with aCSF (n = 8) or CIC (n = 10) in the MBH (injection design 2). Data are means ± SEM. *p < 0.05; **p < 0.01. impl., Implantation.
- Figure 3.
Leucine's anorexigenic effect requires direct activation of the melanocortin system. a , Sample traces recorded before and after application of l-leucine from a POMC neuron in current-clamp configuration. b , Immunofluorescence showing colocalization (yellow) of leucine-stimulated c-Fos-positive cells (Cy3, red) and arcuate POMC neurons of POMC-CRE Z/eGFP mice (green), 70 min after MBH leucine administration (injection design 1). c , Quantification of c-Fos-positive cells in different nuclei 70 min after MBH aCSF or leucine injection (injection design 1). d–f , First meal size ( d ), 12 h food intake ( e ), and 24 h change in body weight (BW) ( f ) in mouse (n = 8–12) after MBH coadministration of SHU9119 or aCSF and leucine or aCSF (injection design 3). Data are means ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001.
- Figure 4.
Oxytocin receptor antagonist blocks leucine anorexigenic effect. a–d , First meal size ( a ), food intake ( b ), meal size ( c ), and meal number ( d ) in mouse (n = 9) after coadministration of IVth intracerebroventricular OVT or aCSF and MBH leucine or aCSF (injection design 5). Data are means ± SEM. *p < 0.05; **p < 0.01.
- Figure 5.
MBH leucine activates Erk1/2 signaling pathway in MBH, PVN oxytocin, and DVC neurons. a–c , MBH ( a ), PVN ( b ), and DVC ( c ) Erk1/2 Thr202/Tyr204 phosphorylation and CREB Ser133 phosphorylation in mouse 30 min after an MBH injection of aCSF (n = 5) or leucine (n = 5) (injection design 1). d , Immunofluorescence showing colocalization (yellow, right) of oxytocin (Cy2, green, left) and MBH leucine-induced phospho-Thr202/Tyr204 Erk1/2 (Cy3, red, middle) in PVN slices of mice 30 min after MBH leucine administration (injection design 1).
- Figure 6.
MBH leucine anorexigenic effect requires MBH Erk1/2 signaling. a–e , First meal size ( a ), 24 h food intake ( b ), 24 h change in body weight (BW) ( c ), MBH Erk1/2 Thr202/Tyr204 phosphorylation ( d ), and MBH p70 S6 kinase 1 Thr389 phosphorylation ( e ) in mouse (n = 6–12) after MBH coadministration of U0126 or its vehicle and leucine or aCSF (injection design 7). All data are means ± SEM. *p < 0.05; **p < 0.01.
- Figure 7.
Model for MBH leucine's sensing regulation of feeding behavior. Acute increase in MBH leucine levels engages a forebrain/hindbrain neurocircuit to decrease meal size through the activation of MBH POMC neurons, PVN oxytocin neurons, and NTS neurons involved in the regulation of feeding.
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