Evidence that leptin-induced weight loss requires activation of both forebrain and hindbrain receptors

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)83-92
Number of pages10
JournalPhysiology and Behavior
Volume120
DOIs
StatePublished - Jan 1 2013

Fingerprint

Rhombencephalon
Prosencephalon
Leptin
Weight Loss
Leptin Receptors
Fourth Ventricle
Third Ventricle
Energy Metabolism
Fats
Body Composition
Weight Gain
Eating

Keywords

  • Carcass fat
  • Energy expenditure
  • Food intake
  • Leptin mutein protein

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience

Cite this

@article{3156889cb6374bb1b6d773a30b834775,
title = "Evidence that leptin-induced weight loss requires activation of both forebrain and hindbrain receptors",
abstract = "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.",
keywords = "Carcass fat, Energy expenditure, Food intake, Leptin mutein protein",
author = "Harris, {Ruth Babette}",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.physbeh.2013.07.004",
language = "English (US)",
volume = "120",
pages = "83--92",
journal = "Physiology and Behavior",
issn = "0031-9384",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Evidence that leptin-induced weight loss requires activation of both forebrain and hindbrain receptors

AU - Harris, Ruth Babette

PY - 2013/1/1

Y1 - 2013/1/1

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

UR - http://www.scopus.com/inward/record.url?scp=84882761362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882761362&partnerID=8YFLogxK

U2 - 10.1016/j.physbeh.2013.07.004

DO - 10.1016/j.physbeh.2013.07.004

M3 - Article

C2 - 23911693

AN - SCOPUS:84882761362

VL - 120

SP - 83

EP - 92

JO - Physiology and Behavior

JF - Physiology and Behavior

SN - 0031-9384

ER -