Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents

2003 ◽  
Vol 79 (4-5) ◽  
pp. 761-766 ◽  
Author(s):  
S BENOIT ◽  
E AIR ◽  
K WILMER ◽  
P MESSERSCHMIDT ◽  
K HODGE ◽  
...  
2020 ◽  
Author(s):  
Paul V. Sabatini ◽  
Henriette Frikke-Schmidt ◽  
Joe Arthurs ◽  
Desiree Gordian ◽  
Anita Patel ◽  
...  

AbstractTo determine the function and mechanisms of action for hindbrain neurons that express GFRAL, the receptor for the anorexigenic peptide, GDF-15, we generated Gfralcre and conditional GfralCreERT mice. While signals of infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons, the artificial activation of GfralCre- expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). Additionally, activation of the smaller population of GFRAL neurons captured by the GfralCreERT allele decreased gastric emptying and produced a CTA without suppressing food intake, suggesting that GFRAL neurons primarily modulate gastric physiology and stimulate aversive responses. GFRAL neurons most strongly innervated the parabrachial nucleus (PBN), where they targeted CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated, pathophysiologic signals to the aversive suppression of nutrient uptake and absorption.


2008 ◽  
Vol 294 (2) ◽  
pp. R352-R361 ◽  
Author(s):  
Susan Aja ◽  
Leslie E. Landree ◽  
Amy M. Kleman ◽  
Susan M. Medghalchi ◽  
Aravinda Vadlamudi ◽  
...  

Inhibition of brain carnitine palmitoyl-transferase-1 (CPT-1) is reported to decrease food intake and body weight in rats. Yet, the fatty acid synthase (FAS) inhibitor and CPT-1 stimulator C75 produces hypophagia and weight loss when given to rodents intracerebroventricularly (icv). Thus roles and relative contributions of altered brain CPT-1 activity and fatty acid oxidation in these phenomena remain unclarified. We administered compounds that target FAS or CPT-1 to mice by single icv bolus and examined acute and prolonged effects on feeding and body weight. C75 decreased food intake rapidly and potently at all doses (1–56 nmol) and dose dependently inhibited intake on day 1. Dose-dependent weight loss on day 1 persisted through 4 days of postinjection monitoring. The FAS inhibitor cerulenin produced dose-dependent (560 nmol) hypophagia for 1 day, weight loss for 2 days, and weight regain to vehicle control by day 3. The CPT-1 inhibitor etomoxir (32, 320 nmol) did not alter overall day 1 feeding. However, etomoxir attenuated the hypophagia produced by C75, indicating that CPT-1 stimulation is important for C75's effect. A novel compound, C89b, was characterized in vitro as a selective stimulator of CPT-1 that does not affect fatty acid synthesis. C89b (100, 320 nmol) decreased feeding in mice for 3 days and produced persistent weight loss for 6 days without producing conditioned taste aversion. Similarly, intraperitoneal administration decreased feeding and body weight without producing conditioned taste aversion. These results suggest a role for brain CPT-1 in the regulation of energy balance and implicate CPT-1 stimulation as a pharmacological approach to weight loss.


2013 ◽  
Vol 110-111 ◽  
pp. 13-19 ◽  
Author(s):  
Rojo Rasoamanana ◽  
Patrick C. Even ◽  
Nicolas Darcel ◽  
Daniel Tomé ◽  
Gilles Fromentin

Diabetes ◽  
2002 ◽  
Vol 51 (11) ◽  
pp. 3196-3201 ◽  
Author(s):  
D. J. Clegg ◽  
M. D. Wortman ◽  
S. C. Benoit ◽  
C. C. McOsker ◽  
R. J. Seeley

Peptides ◽  
2000 ◽  
Vol 21 (3) ◽  
pp. 345-351 ◽  
Author(s):  
Stephen C Benoit ◽  
Todd E Thiele ◽  
Stephen C Heinrichs ◽  
Paul A Rushing ◽  
Kathleen A Blake ◽  
...  

2006 ◽  
Vol 147 (1) ◽  
pp. 109-116 ◽  
Author(s):  
Adam P Chambers ◽  
Henry S Koopmans ◽  
Quentin J Pittman ◽  
Keith A Sharkey

2014 ◽  
Vol 307 (6) ◽  
pp. R737-R745 ◽  
Author(s):  
Emily E. Noble ◽  
Charles J. Billington ◽  
Catherine M. Kotz ◽  
ChuanFeng Wang

Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin.


1981 ◽  
Vol 240 (5) ◽  
pp. R310-R318 ◽  
Author(s):  
S. M. Anika ◽  
T. R. Houpt ◽  
K. A. Houpt

Twenty-three pigs, 1-3 mo of age, were fitted variously with intraperitoneal, intrajugular, intraportal, and intraduodenal catheters. After a 4-h fast, porcine cholecystokinin (CCK), 5-40 Ivy dog units/kg body wt (IDU/kg); caerulein, 0.25-2 micrograms/kg; or the octapeptide of cholecystokinin (CCK-OP), 5-40 IDU/kg, was given parenterally; or 2-5% sodium oleate or 5% protein hydrolysate (5 ml/kg) was injected intraduodenally. Pelleted feed intake was then measured for 10 min. Food intake was depressed in a dose-related fashion in all instances as compared to after 0.9% NaCl control injections. For example, feed consumption following 5 and 40 IDU/kg of CCK intrajugularly was 84 +/- 2 and 6 +/- 4 (SE) %, respectively, of control intake. Intraportal infusion produced a greater depression of feeding. A conditioned taste aversion could not be formed to CCK, caerulein, or CCK-OP. Sodium oleate or protein hydrolysate, releasers of endogenous CCK, depressed feeding, and this satiety effect was attenuated when given with 0.5% tetracaine. The results support the hypothesis that CCK participates in rapid, presumably preabsorptive, satiety.


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