Leptin regulates the reward value of nutrient

被引:185
作者
Domingos, Ana I. [1 ]
Vaynshteyn, Jake [1 ]
Voss, Henning U. [2 ]
Ren, Xueying [3 ,4 ]
Gradinaru, Viviana [5 ]
Zang, Feng [5 ]
Deisseroth, Karl [5 ,6 ,7 ,8 ]
de Araujo, Ivan E. [3 ]
Friedman, Jeffrey [1 ,9 ]
机构
[1] Rockefeller Univ, Mol Genet Lab, New York, NY 10021 USA
[2] Weill Cornell Med Coll, Dept Radiol, New York, NY USA
[3] Yale Univ, Sch Med, JB Pierce Lab, New Haven, CT USA
[4] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA
[5] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA
[6] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA
[7] Stanford Univ, CNC Program, Stanford, CA 94305 USA
[8] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA
[9] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
基金
美国国家卫生研究院;
关键词
SWEET TASTE; ORBITOFRONTAL CORTEX; WANTING FOOD; WEIGHT-LOSS; DOPAMINE; NEURONS; BRAIN; SUCROSE; RESTRICTION; CIRCUITRY;
D O I
10.1038/nn.2977
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake.
引用
收藏
页码:1562 / U92
页数:8
相关论文
共 45 条
[1]   Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite [J].
Abizaid, Alfonso ;
Liu, Zhong-Wu ;
Andrews, Zane B. ;
Shanabrough, Marya ;
Borok, Erzsebet ;
Elsworth, John D. ;
Roth, Robert H. ;
Sleeman, Mark W. ;
Picciotto, Marina R. ;
Tschop, Matthias H. ;
Gao, Xiao-Bing ;
Horvath, Tamas L. .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (12) :3229-3239
[2]   BITTER TASTE OF SACCHARIN RELATED TO THE GENETIC ABILITY TO TASTE THE BITTER SUBSTANCE 6-NORMAL-PROPYLTHIOURACIL [J].
BARTOSHUK, LM .
SCIENCE, 1979, 205 (4409) :934-935
[3]   Intense sweeteners, energy intake and the control of body weight [J].
Bellisle, F. ;
Drewnowski, A. .
EUROPEAN JOURNAL OF CLINICAL NUTRITION, 2007, 61 (06) :691-700
[4]   Measuring hedonic impact in animals and infants: microstructure of affective taste reactivity patterns [J].
Berridge, KC .
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 2000, 24 (02) :173-198
[5]   The debate over dopamine's role in reward: the case for incentive salience [J].
Berridge, Kent C. .
PSYCHOPHARMACOLOGY, 2007, 191 (03) :391-431
[6]   'Liking' and 'wanting' food rewards: Brain substrates and roles in eating disorders [J].
Berridge, Kent C. .
PHYSIOLOGY & BEHAVIOR, 2009, 97 (05) :537-550
[7]   EFFECTS OF SUCROSE, CAFFEINE, AND COLA BEVERAGES ON OBESITY, COLD RESISTANCE, AND ADIPOSE-TISSUE CELLULARITY [J].
BUKOWIECKI, LJ ;
LUPIEN, J ;
FOLLEA, N ;
JAHJAH, L .
AMERICAN JOURNAL OF PHYSIOLOGY, 1983, 244 (04) :R500-R507
[8]   The effects of prolonged caloric restriction leading to weight-loss on food hedonics and reinforcement [J].
Cameron, Jameason D. ;
Goldfield, Gary S. ;
Cyr, Marie Josee ;
Doucet, Eric .
PHYSIOLOGY & BEHAVIOR, 2008, 94 (03) :474-480
[9]   Food reward in the absence of taste receptor signaling [J].
de Araujo, Ivan E. ;
Oliveira-Maia, Albino J. ;
Sotnikova, Tatyana D. ;
Gainetdinov, Raul R. ;
Caron, Marc G. ;
Nicolelis, Miguel A. L. ;
Simon, Sidney A. .
NEURON, 2008, 57 (06) :930-941
[10]   Effects of deprivation on hedonics and reinforcing value of food [J].
Epstein, LH ;
Truesdale, R ;
Wojcik, A ;
Paluch, RA ;
Raynor, HA .
PHYSIOLOGY & BEHAVIOR, 2003, 78 (02) :221-227