TY - JOUR
T1 - Evidence that leptin-induced weight loss requires activation of both forebrain and hindbrain receptors
AU - Harris, Ruth B.S.
N1 - Funding Information:
This work was supported by NIH grant DK059303 awarded to R.B.S. Harris.
PY - 2013
Y1 - 2013
N2 - Previous studies with chronic decerebrate rats and rats infused with leptin into the 4th ventricle suggest that hindbrain leptin receptors attenuate the catabolic effect of forebrain leptin receptor activation. To test this further, rats were fitted with both 3rd and 4th ventricle cannulae. They were infused for 12. days with different combinations of saline, low dose leptin or leptin receptor antagonist (leptin mutein protein). Infusion of 0.1. μg leptin/day into the 3rd ventricle or 0.6. μg leptin/day into the 4th ventricle had no significant effect on food intake, energy expenditure or body composition. Infusion of 2. μg mutein/day into either ventricle caused a small, but significant weight gain. When mutein was infused into one ventricle and leptin into the other, the rats lost weight irrespective of which combination was applied. Surprisingly, rats that received leptin infusions into both ventricles showed an initial hypophagia, no change in energy expenditure, but a 75% loss of carcass fat after 12. days. These data suggest that neuronal pathways activated by leptin receptors in either the forebrain or hindbrain modulate each other's effects. In normal conditions hindbrain leptin may attenuate the catabolic effect of forebrain leptin, but if activity in one area is blocked with mutein, then the catabolic response to leptin in the other ventricle is exaggerated. When receptors in both areas are activated there is an integration of response to produce negative energy balance. This may ensure that leptin causes a loss of fat only when leptin is elevated in both the CSF and periphery.
AB - Previous studies with chronic decerebrate rats and rats infused with leptin into the 4th ventricle suggest that hindbrain leptin receptors attenuate the catabolic effect of forebrain leptin receptor activation. To test this further, rats were fitted with both 3rd and 4th ventricle cannulae. They were infused for 12. days with different combinations of saline, low dose leptin or leptin receptor antagonist (leptin mutein protein). Infusion of 0.1. μg leptin/day into the 3rd ventricle or 0.6. μg leptin/day into the 4th ventricle had no significant effect on food intake, energy expenditure or body composition. Infusion of 2. μg mutein/day into either ventricle caused a small, but significant weight gain. When mutein was infused into one ventricle and leptin into the other, the rats lost weight irrespective of which combination was applied. Surprisingly, rats that received leptin infusions into both ventricles showed an initial hypophagia, no change in energy expenditure, but a 75% loss of carcass fat after 12. days. These data suggest that neuronal pathways activated by leptin receptors in either the forebrain or hindbrain modulate each other's effects. In normal conditions hindbrain leptin may attenuate the catabolic effect of forebrain leptin, but if activity in one area is blocked with mutein, then the catabolic response to leptin in the other ventricle is exaggerated. When receptors in both areas are activated there is an integration of response to produce negative energy balance. This may ensure that leptin causes a loss of fat only when leptin is elevated in both the CSF and periphery.
KW - Carcass fat
KW - Energy expenditure
KW - Food intake
KW - Leptin mutein protein
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U2 - 10.1016/j.physbeh.2013.07.004
DO - 10.1016/j.physbeh.2013.07.004
M3 - Article
C2 - 23911693
AN - SCOPUS:84882761362
SN - 0031-9384
VL - 120
SP - 83
EP - 92
JO - Physiology and Behavior
JF - Physiology and Behavior
ER -