Logging out of EU Login will log you out of any other services that use your EU Login account. Use the CORDIS log out button to remain logged in on other services. Overweight and obesity have become a major health problem and their prevalence is accelerating dramatically in Europe and the rest of the world.

This project aims to deliver European expert scientists which are urgently required in the field of feeding behaviour and satiety control. Scientific expertise: The EST will provide early-stage researchers with a structured training programme on feeding behaviour and control of food intake and appetite in three top European institutes located in Paris, Munich, and London, and they will also have access to one of the biggest European food industries.

The synergy provided by this multiple partnership will represent an important added value by covering the latest experimental, theoretical and applied aspects. Career development: A Personal Career Development Plan PCDP will be established to aid the early-stage researchers to pursue a career in this important area for the European community.

This plan will prepare the earlystage researchers for future careers inacademic institutes, the food or pharmaceutical industries, or governmental and non governmental organisations. Such screening models are currently not available and highly needed, both in the food as in the pharmaceutical industry.

The international network developed by NuSISCO will translate into enhanced career choices and greater employment opportunities. This programme will enhance inter-sectorial collaborations to overcome fragmentation within European Research and will also contribute to two science and technology priority areas of the ERA as outlined in the Framework VI programme: 1 life sciences, genomics and biotechnology for health, and 2 food quality and safety.

FPMOBILITY-2 See other projects for this call. Close X. Select your language. Deutsch English español français italiano polski. Log out Logging out of EU Login will log you out of any other services that use your EU Login account.

Log out EU Login Log out. English EN. Group information One line of research in our group started with the study of brain metabolic sensors and their relationship with peptides regulating food intake, especially glucagon-related peptides GLP-1, GLP Strategic objectives To study the role of the metabolic sensor PASK in adaptation to nutritional changes, analysing its role in glucose and lipid metabolism.

To study the role of PASK and other metabolic sensors in thermogenesis. To analyse the hypothalamus-brown adipose tissue intercommunication To study possible links between insulin resistance, glucose hypometabolism, and neurodegenerative diseases.

To analyse brain glucose metabolism and insulin resistance in animals with tauopathy. To identify mutations associated with the monogenic diabetes MODY and study the regulation of the proteins involved. Lines of research Studies of the relationship between insulin resistance and neurodegenerative diseases at the molecular level and with PET imaging.

Treatment with insulin sensitising agents metformin and pioglitazone. Expression of brain glucose hypometabolism and insulin resistance in tauopathy transgenic mice. Effect of GLP-2 on proliferation and apoptosis of rat astrocyte cultures. Study of the role of metabolic sensors in the regulation of thermogenesis.

Hypothalamus-brown adipose tissue intercommunication Molecular diagnosis of monogenic diabetes MODY and study the regulation of the proteins involved. Other members of the group. Publications Search by year. Other research groups in this area Medical Physics.

Endocrinology of Metabolic Diseases. Diabetes and Cardiovascular. However, we did not see any overlap between these two neuronal populations Fig. We then asked whether this DTK—TAKR99D—IPC circuitry had active synaptic transmissions.

Since this DTK—TAKR99D—IPC circuitry could be activated by D-glucose in the ex vivo brain preparations, in the absence of peripheral sensory organs, we reasoned that it might function as an internal glucose sensor. More specifically, we hypothesized that during the actual feeding episodes this neural circuitry could be activated by ingested nutrients and rapidly impose a suppressive effect on food consumption, ensuring the appropriate amount of food being ingested.

S10a and IPCs Fig. It is likely that during these feeding episodes, dietary D-glucose was quickly absorbed and transported into the hemolymph and activated DTK—TAKR99D—IPC circuitry. a Schematic diagram of the in vivo calcium imaging preparations. Horizontal black bars represent the feeding episodes.

m A working model. During the ingestion of nutritive sugars e. IPCs, as the satiety center, cease food intake behaviors via its downstream neural circuitry. IPCs exhibited strong calcium responses to D-glucose feeding in the same experiments Supplementary information, Fig.

S11b, e. Therefore, DTK—TAKR99D—IPC circuitry could rapidly sense the dietary intake of D-glucose and hence the satiety state, in the time scale of seconds. S9 than in the in vivo setup Fig. This seems to be a common problem for ex vivo calcium imaging experiments in the fly brain 8 , 19 , 20 and we speculated that this might be due to differences in the kinetics of stimulus penetration.

Similarly, in flies bearing mutations in Dtk and Takr99d genes, IPCs exhibited much reduced calcium responses to D-glucose Fig. These results suggest that DTK—TAKR99D signaling is required for the DTK—TAKR99D—IPC circuitry to function as a satiety sensor, sensing D-glucose and in turn suppressing food consumption.

Conversely, activating IPCs reduced food consumption Fig. In summary, our work has identified a novel satiety sensor in the fly brain that can sense the increase in circulating glucose during food ingestion and suppress further food intake.

This circuitry can rapidly feed the information of the satiety state to IPCs and prevent flies from overfeeding, thereby contributing to the maintenance of energy homeostasis in flies Fig. It will be of great interest to further study how this novel satiety sensor rapidly responds to the rise and fall of circulating D-glucose during a meal and modulate food consumption in a timely manner.

Our present study uncovers a novel pathway of satiety sensing in fruit flies. Future studies are needed to understand how it interacts with other satiety sensors, especially other sugar-sensing pathways that also target IPCs directly or indirectly.

Virgin female flies were collected shortly after eclosion and kept on food for 5—7 days till experiments. All UAS-RNAi lines used in the screening , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , UAS-TK RNAi , elav-GAL4 , TAKR MB , TAKR MI , DTK MI , DTK f , UAS-mCDGFP , LexAop-rCD2RFP,UAS-mCD8GFP , UAS-GCaMP6m , LexAop-GCaMP6m , UAS-nSyb-spGFP1—10,LexAop-CD4-spGFP11 , LexAop-nSyb-spGFP1—10,UAS-CD4-spGFP11 , and dilp2-GAL4 were obtained from the Bloomington Drosophila Stock Center at Indiana University.

UAS-dTRPA1 , UAS-C3PA-GFP,UAS-Shi ts , and UAS-CsChrimson were from David Anderson Caltech. dilp2-LexA was a gift from Zhefeng Gong Zhejiang University, China. All flies were backcrossed for at least six generations before use to ensure that the genetic backgrounds were comparable.

The food stimulation was repeated until the flies became unresponsive to a series of ten food stimuli, and the total food consumption was calculated afterwards. The PER assay was conducted as described previously. Flies showing PER responses to at least one of the two trials were considered positive to that sugar concentration.

As described in our previous work, 39 the locomotor activity of individual flies was monitored using DAMS Trikinetics. These tubes were inserted into DAMS monitors and kept in incubators during experiments. The frequency of these flies to walk across the infrared beam placed in the center of the tubes was collected as an indirect measure of their locomotion.

Flies were immobilized as previously described. The glass micropipette was pulled from thick-walled borosilicate capillaries Sutter Instruments, BF with a micromanipulator Sutter Instruments, MP to control its movements. Two-choice behavioral assay was conducted as previously described. of flies ate both — No.

of flies ate either or both sugars. For the ex vivo calcium imaging preparations, adult fly brains were dissected in the sugar-free AHL buffer and mounted on Poly-L-Lysine PLL; Sigma Aldrich, P coated cover glass. For experiments shown in Fig.

The first 20 frames were recorded when perfusing sugar-free AHL as the baseline, the next 40 frames were recorded during D-glucose perfusion, and the last 40 frames were recorded during AHL washout.

Afterwards, the next frames were recorded during D-glucose perfusion and the following frames were recorded during AHL washout. For in vivo calcium imaging preparations, 19 adult flies were anesthetized on ice and then glued onto a transparent tape.

The cuticle of the dorsal part of the fly head was gently removed with forceps and the exposed brain was bathed in the sugar-free AHL. Liquid food was delivered to the proboscis of flies by a micromanipulator Sutter Instruments, MP The flies were illuminated by an IR LED Thorlabs, ML3 and the feeding behavior was imaged by a CMOS camera FLIR USB 2.

Image analyses were performed in ImageJ and plotted in Graphpad Prism 6 or Matlab MathWorks. The fixed samples were washed with Washing Buffer 0.

This step was followed by ethanol dehydration and xylene clearing, and DPX was then added to the brain side of the cover glass. The samples were finally mounted on a microscope slide. Antibodies were used at the following dilutions: mouse anti-nc82 , DSHB , rabbit anti-GFP , Life Technologies , rabbit anti-DsRed , ClonTech , mouse anti-GFP , Abcam , Alexa Fluor goat anti-mouse , Life Technologies , Alexa Fluor goat anti-rabbit , Life Technologies , Alexa Fluor goat anti-mouse , Life Technologies , Alexa Fluor goat anti-rabbit , Life Technologies.

After fixation, the samples were washed, mounted and dehydrated as described in the immunohistochemistry experiment. PA-GFP experiments were performed with a two-photon laser-scanning microscope Olympus.

Three-dimensional images were reconstructed using Fiji software. The obtained heads and bodies were homogenized and the total RNA was purified with TRIzol Reagent Life Technologies. The eluted RNA products were then reverse-transcribed with TransScript cDNA Synthesis SuperMix TransGen.

The quantitative PCR experiments were performed using a CFX96 Real-Time System Biorad. To activate the neurons expressing CsChrimson, flies were dissected and mounted as described in ex vivo calcium imaging experiments. The post hoc test with Bonferroni correction was performed for multiple comparisons following ANOVA.

For the RNAi screening Fig. Krashes, M. Melanocortin-4 receptor-regulated energy homeostasis. Google Scholar. Kim, K. Signalling from the periphery to the brain that regulates energy homeostasis.

Kim, S. Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells. Nature , — Nassel, D. Pool, A. Feeding regulation in Drosophila. Chantranupong, L.

Nutrient-sensing mechanisms across evolution. Cell , 67—83 Cell Mol. Life Sci. Oh, Y. et al. A glucose-sensing neuron pair regulates insulin and glucagon in Drosophila. Maniere, G. Direct sensing of nutrients via a LAT1-like transporter in Drosophila insulin-producing cells.

Cell Rep. Miyamoto, T. A fructose receptor functions as a nutrient sensor in the Drosophila brain. Cell , — Diverse roles for the Drosophila fructose sensor Gr43a. Fly 8 , 19—25 Kapan, N. Identified peptidergic neurons in the Drosophila brain regulate insulin-producing cells, stress responses and metabolism by coexpressed short neuropeptide F and corazonin.

Rajan, A. Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Sun, J. Drosophila FIT is a protein-specific satiety hormone essential for feeding control.

Delanoue, R. Drosophila insulin release is triggered by adipose Stunted ligand to brain Methuselah receptor. Science , — Recent advances in neuropeptide signaling in Drosophila , from genes to physiology and behavior.

Qi, W. A quantitative feeding assay in adult Drosophila reveals rapid modulation of food ingestion by its nutritional value. Brain 8 , 87 Ja, W.

Group information Strategic objectives Lines of research Members of the group Publications Projects. Biochemistry and Molecular Biology and Secc Dptal Cell Biology. Faculty of Medicine Faculty of Medicine, Complutense University of Madrid Pl.

Group information One line of research in our group started with the study of brain metabolic sensors and their relationship with peptides regulating food intake, especially glucagon-related peptides GLP-1, GLP Strategic objectives To study the role of the metabolic sensor PASK in adaptation to nutritional changes, analysing its role in glucose and lipid metabolism.

To study the role of PASK and other metabolic sensors in thermogenesis. To analyse the hypothalamus-brown adipose tissue intercommunication To study possible links between insulin resistance, glucose hypometabolism, and neurodegenerative diseases.

To analyse brain glucose metabolism and insulin resistance in animals with tauopathy. To identify mutations associated with the monogenic diabetes MODY and study the regulation of the proteins involved. Lines of research Studies of the relationship between insulin resistance and neurodegenerative diseases at the molecular level and with PET imaging.

Treatment with insulin sensitising agents metformin and pioglitazone. Expression of brain glucose hypometabolism and insulin resistance in tauopathy transgenic mice. Effect of GLP-2 on proliferation and apoptosis of rat astrocyte cultures. Study of the role of metabolic sensors in the regulation of thermogenesis.

Hypothalamus-brown adipose tissue intercommunication Molecular diagnosis of monogenic diabetes MODY and study the regulation of the proteins involved. Other members of the group. Publications Search by year. Some were mainly found in the stomach and others located primarily in different parts of the intestines, but each type was specialized to sense a particular combination of nutrient-related hormones.

The results suggested that stretch-sensitive IGLEs also came in at least two different types, one mainly in the stomach and the other primarily in the intestine. To learn how these different nerve types in the gut might control appetite, Bai and colleagues used a technique called optogenetics to switch individual types of neurons on and off.

The technique involves genetically engineering specific groups of neurons so that they can then be selectively stimulated by light. This allowed the team to test the ability of different types of neuron to stop hungry mice from eating.

As expected, the researchers found that stimulating IGLE neurons that sense stomach stretch in the mice effectively halted eating. Even more surprisingly, the experiments showed that stimulating IGLE stretch receptors in the intestine had an even more profound effect on reducing appetite in hungry animals than stimulating the stomach stretch receptors.

The findings also suggest a potential explanation for why bariatric surgery, which is used to treat extreme obesity, is so effective at modulating appetite and reducing weight. The surgery effectively reduces the size of the gut, and researchers have suspected that one reason why the procedure is so effective at blocking hunger is that it causes food to pass very rapidly from the stomach into the intestine.

The new findings suggest that rather than overloading nutrient receptors, the rapid passage of food stretches the intestine, activating the vagal stretch sensors and so blocking feeding. Facebook Linkedin RSS Twitter Youtube. Sign in. your username. Topic s MOBILITY Call for proposal FPMOBILITY-2 See other projects for this call.

Funding Scheme EST - Marie Curie actions-Early-stage Training. Website Opens in new window. EU contribution. Participants 3 Sort alphabetically. Sort by EU Contribution. Expand all Collapse all. Exhibition road, south kensington campus London See on map.

Other funding. Arcisstrasse 21 Muenchen See on map. UNILEVER NEDERLAND B. Weena Rotterdam See on map. Share this page. Download XML PDF. Last update: 26 May Booklet My Booklet. This site uses cookies to offer you a better browsing experience.

The new findings suggest that rather than overloading nutrient receptors, the rapid passage of food stretches the intestine, activating the vagal stretch sensors and so blocking feeding. Facebook Linkedin RSS Twitter Youtube. Sign in. your username.

your password. Forgot your password? Get help. Privacy Policy. Password recovery. your email. GEN — Genetic Engineering and Biotechnology News. Home News Intestinal Stretch Tells Brain to Switch Off Appetite.

Anatomy Animal models Cells Cellular, Molecular and Developmental Biology Disease models DNA sequencing Sequencing Medicine, Diagnosis, and Therapeutics Mice Molecular biology Nervous system Neural pathway Neurons Next-generation sequencing Sequencing Nucleic acid sequencing Research and development Sequencing Single cell sequencing.

Song, W. Control of lipid metabolism by tachykinin in Drosophila. Asahina, K. Tachykinin-expressing neurons control male-specific aggressive arousal in Drosophila. Kitamoto, T. Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons.

Rosenzweig, M. The Drosophila ortholog of vertebrate TRPA1 regulates thermotaxis. Genes Dev. Chen, T.

Ultrasensitive fluorescent proteins for imaging neuronal activity. Macpherson, L. Dynamic labelling of neural connections in multiple colours by trans-synaptic fluorescence complementation. Ko, K. Starvation promotes concerted modulation of appetitive olfactory behavior via parallel neuromodulatory circuits.

Elife 4 , e Ruta, V. A dimorphic pheromone circuit in Drosophila from sensory input to descending output. Kahsai, L. Neuropeptides in the Drosophila central complex in modulation of locomotor behavior. Birse, R. Regulation of insulin-producing cells in the adult Drosophila brain via the tachykinin peptide receptor DTKR.

Klapoetke, N. Independent optical excitation of distinct neural populations. Methods 11 , — Yapici, N. A taste circuit that regulates ingestion by integrating food and hunger signals.

Ro, J. FLIC: high-throughput, continuous analysis of feeding behaviors in Drosophila. PLoS ONE 9 , e Park, S. A genetic strategy to measure circulating Drosophila insulin reveals genes regulating insulin production and secretion. PLoS Genet. Zhan, Y.

Taotie neurons regulate appetite in Drosophila. Deshpande, S. Quantifying Drosophila food intake: comparative analysis of current methodology. Octopamine mediates starvation-induced hyperactivity in adult Drosophila. Deng, B. Chemoconnectomics: mapping chemical transmission in Drosophila.

Neuron , — Download references. We thank all Wang Lab members for helpful discussions and technical assistance. We thank the Bloomington Drosophila stock center at Indiana University and the Tsinghua Fly Center for fly stocks and reagents. We thank Yulong Li and Jianzhi Zeng for their help with the in vivo calcium imaging preparations.

We thank Neuroscience Pioneer Club for insightful discussions throughout the course of this study. Danping Chen and Ye Wu provided scientific and administrative support in the laboratory.

Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China. You can also search for this author in PubMed Google Scholar. and L. designed the experiments and wrote the manuscript with the input from G. conducted all experiments and data analysis with the help of G.

supervised the project. Correspondence to Liming Wang. Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. A novel satiety sensor detects circulating glucose and suppresses food consumption via insulin-producing cells in Drosophila.

Cell Res 31 , — Download citation. Received : 23 February Accepted : 26 October Published : 03 December Issue Date : May Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Cellular and Molecular Life Sciences Skip to main content Thank you for visiting nature. nature cell research articles article. Download PDF. Subjects Calcium signalling Nutrient signalling. Abstract Sensing satiety is a crucial survival skill for all animal species including human.

Introduction Sensing hunger and satiety is crucial to ensure appropriate and balanced intake of energy and essential nutrients. Results and discussion A behavioral RNAi screening identified DTK—TAKR99D signaling as a potent feeding suppressor To identify neuropeptidergic cues that indicated the internal satiety state and suppressed food consumption in turn, we carried out a neuron-specific RNAi screening in adult flies by using our previously developed MAFE Ma nual Fe eding assay to examine food consumption.

Full size image. The PER assay The PER assay was conducted as described previously. Locomotion assay As described in our previous work, 39 the locomotor activity of individual flies was monitored using DAMS Trikinetics.

AHL injection Flies were immobilized as previously described. Two-choice feeding assay Two-choice behavioral assay was conducted as previously described. Calcium imaging For the ex vivo calcium imaging preparations, adult fly brains were dissected in the sugar-free AHL buffer and mounted on Poly-L-Lysine PLL; Sigma Aldrich, P coated cover glass.

PA-GFP PA-GFP experiments were performed with a two-photon laser-scanning microscope Olympus. References Krashes, M. Google Scholar Kim, K. Google Scholar Kim, S. Google Scholar Nassel, D. Google Scholar Pool, A.

Google Scholar Chantranupong, L. Google Scholar Oh, Y. Google Scholar Maniere, G. Google Scholar Miyamoto, T. Google Scholar Kapan, N. Google Scholar Rajan, A. Google Scholar Sun, J. Google Scholar Delanoue, R.

Google Scholar Qi, W. Google Scholar Ja, W. Google Scholar Yang, Z. Google Scholar Dus, M. Google Scholar Song, W. Google Scholar Asahina, K. Google Scholar Kitamoto, T.

Google Scholar Rosenzweig, M. Google Scholar Chen, T. Shen M, Jiang C, Liu P, Wang F, Ma L. Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward.

Transl Psychiatry 6 12 :e Morales M, Margolis EB. Ventral tegmental area: cellular heterogeneity, connectivity and behaviour. Nat Rev Neurosci 18 2 — Bromberg-Martin ES, Matsumoto M, Hikosaka O. Dopamine in motivational control: rewarding, aversive, and alerting.

Neuron 68 5 — Bariselli S, Glangetas C, Tzanoulinou S, Bellone C. Ventral tegmental area subcircuits process rewarding and aversive experiences. J Neurochem 6 — Cohen JY, Haesler S, Vong L, Lowell BB, Uchida N. Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature —8.

Mikhailova MA, Bass CE, Grinevich VP, Chappell AM, Deal AL, Bonin KD, et al. Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors.

Neuroscience — Lammel S, Ion DI, Roeper J, Malenka RC. Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron — Root DH, Mejias-Aponte CA, Qi J, Morales M. Role of glutamatergic projections from ventral tegmental area to lateral habenula in aversive conditioning.

J Neurosci 34 42 — Stamatakis AM, Jennings JH, Ung RL, Blair GA, Weinberg RJ, Neve RL, et al. A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward.

Neuron 80 4 — Zahm DS. Functional-anatomical implications of the nucleus accumbens core and shell subterritories. Ann N Y Acad Sci — Wheeler RA, Aragona BJ, Fuhrmann KA, Jones JL, Day JJ, Cacciapaglia F, et al.

Cocaine cues drive opposing context-dependent shifts in reward processing and emotional state. Biol Psychiatry 69 11 — Saddoris MP, Cacciapaglia F, Wightman RM, Carelli RM.

Differential dopamine release dynamics in the nucleus accumbens core and shell reveal complementary signals for error prediction and incentive motivation.

J Neurosci 35 33 — Sugam JA, Day JJ, Wightman RM, Carelli RM. Phasic nucleus accumbens dopamine encodes risk-based decision-making behavior.

Biol Psychiatry 71 3 — Salamone JD, Correa M, Farrar A, Mingote SM. Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology Berl 3 — Yager LM, Garcia AF, Wunsch AM, Ferguson SM. The ins and outs of the striatum: role in drug addiction.

Waterson MJ, Horvath TL. Neuronal regulation of energy homeostasis: beyond the hypothalamus and feeding. Cell Metab 22 6 — Haskell-Luevano C, Chen P, Li C, Chang K, Smith MS, Cameron JL, et al. Characterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat 1.

Endocrinology 3 — Colmers WF, Bleakman D. Effects of neuropeptide Y on the electrical properties of neurons. Trends Neurosci 17 9 —9. Tao YX. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology.

Endocr Rev 31 4 — Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein.

Science —8. Yang Y. Structure, function and regulation of the melanocortin receptors. Eur J Pharmacol 1 — Tolle V, Low MJ. In vivo evidence for inverse agonism of agouti-related peptide in the central nervous system of proopiomelanocortin-deficient mice.

Diabetes 57 1 — Nijenhuis WA, Oosterom J, Adan RA. AgRP acts as an inverse agonist on the human-melanocortin-4 receptor. Mol Endocrinol — Wang D, He X, Zhao Z, Feng Q, Lin R, Sun Y, et al. Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons. Front Neuroanat Aponte Y, Atasoy D, Sternson SM.

AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci 14 3 —5. Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N, Grove KL, et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.

Neuron 37 4 — Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis.

EMBO Rep 13 12 — Schaeffer M, Langlet F, Lafont C, Molino F, Hodson DJ, Roux T, et al. Rapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons. Proc Natl Acad Sci U S A 4 —7. Takahashi KA, Cone RD.

Endocrinology 3 —7. Qian S, Chen H, Weingarth D, Trumbauer ME, Novi DE, Guan X, et al. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice.

Mol Cell Biol 22 14 — Wortley KE, Anderson KD, Yasenchak J, Murphy A, Valenzuela D, Diano S, et al. Agouti-related protein-deficient mice display an age-related lean phenotype. Cell Metab 2 6 —7. Luquet S, Perez FA, Hnasko TS, Palmiter RD. Science —5. Gropp E, Shanabrough M, Borok E, Xu AW, Janoschek R, Buch T, et al.

Agouti-related peptide-expressing neurons are mandatory for feeding. Nat Neurosci 8 10 — Bewick GA, Gardiner JV, Dhillo WS, Kent AS, White NE, Webster Z, et al.

Postembryonic ablation of AgRP neurons in mice leads to a lean, hypophagic phenotype. FASEB J 21 3 :1— Bouret SG, Draper SJ, Simerly RB. Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice.

J Neurosci 24 11 — Tong Q, Ye C-P, Jones JE, Elmquist JK, Lowell BB. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat Neurosci 11 9 — Dietrich MO, Zimmer MR, Bober J, Horvath TL.

Hypothalamic Agrp neurons drive stereotypic behaviors beyond feeding. Cell 6 — Nakajima K, Cui Z, Li C, Meister J, Cui Y, Fu O, et al.

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake. Nat Commun Burnett CJ, Li C, Webber E, Tsaousidou E, Xue SY, Brüning JC, et al. Hunger-driven motivational state competition. Neuron 92 1 — Betley JN, Xu S, Cao ZF, Gong R, Magnus CJ, Yu Y, et al. Neurons for hunger and thirst transmit a negative-valence teaching signal.

Nature —5. Chen Y, Lin YC, Kuo TW, Knight ZA. Sensory detection of food rapidly modulates arcuate feeding circuits. Cell 5 — Chen Y, Lin YC, Zimmerman CA, Essner RA, Knight ZA. Hunger neurons drive feeding through a sustained, positive reinforcement signal.

Elife 5:e Dietrich MO, Bober J, Ferreira JG, Tellez LA, Mineur YS, Souza DO, et al. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors.

Nat Neurosci 15 8 — Brown RSE, Kokay IC, Phillipps HR, Yip SH, Gustafson P, Wyatt A, et al. Conditional deletion of the prolactin receptor reveals functional subpopulations of dopamine neurons in the arcuate nucleus of the hypothalamus.

J Neurosci 36 35 — Zhang X, van den Pol AN. Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis. Nat Neurosci 19 10 —7. Stuber GD, Wise RA.

Lateral hypothalamic circuits for feeding and reward. Nat Neurosci 19 2 — Stamatakis AM, Van Swieten M, Basiri ML, Blair GA, Kantak P, Stuber GD. Lateral hypothalamic area glutamatergic neurons and their projections to the lateral habenula regulate feeding and reward.

J Neurosci 36 2 — Navarro M, Olney JJ, Burnham NW, Mazzone CM, Lowery-Gionta EG, Pleil KE, et al. Lateral hypothalamus GABAergic neurons modulate consummatory behaviors regardless of the caloric content or biological relevance of the consumed stimuli. Neuropsychopharmacology 41 6 — Wu Z, Kim ER, Sun H, Xu Y, Mangieri LR, Li DP, et al.

GABAergic projections from lateral hypothalamus to paraventricular hypothalamic nucleus promote feeding. J Neurosci 35 8 —8. Nieh EH, Matthews GA, Allsop SA, Presbrey KN, Leppla CA, Wichmann R, et al.

Decoding neural circuits that control compulsive sucrose seeking. Cell 3 — Carus-Cadavieco M, Gorbati M, Ye L, Bender F, van der Veldt S, Kosse C, et al. Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking.

Nature —6. Blouin AM, Fried I, Wilson CL, Staba RJ, Behnke EJ, Lam HA, et al. Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction.

Harris GC, Wimmer M, Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature —9. Zhang G-C, Mao L-M, Liu X-Y, Wang JQ. Long-lasting up-regulation of orexin receptor type 2 protein levels in the rat nucleus accumbens after chronic cocaine administration.

J Neurochem 1 —7. Sheng Z, Santiago AM, Thomas MP, Routh VH. Metabolic regulation of lateral hypothalamic glucose-inhibited orexin neurons may influence midbrain reward neurocircuitry. Mol Cell Neurosci — Castro DC, Terry RA, Berridge KC. Neuropsychopharmacology 41 8 — Borgland SL, Chang SJ, Bowers MS, Thompson JL, Vittoz N, Floresco SB, et al.

J Neurosci 29 36 — Gao XB, Van Den Pol AN. Melanin concentrating hormone depresses synaptic activity of glutamate and GABA neurons from rat lateral hypothalamus. J Physiol 1 — Eiler WJA, Chen Y, Slieker LJ, Ardayfio PA, Statnick MA, Witkin JM. Consequences of constitutive deletion of melanin-concentrating hormone-1 receptors for feeding and foraging behaviors of mice.

Behav Brain Res —8. Marsh DJ, Weingarth DT, Novi DE, Chen HY, Trumbauer ME, Chen AS, et al. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Sci U S A 99 5 —5.

Burdakov D, Gerasimenko O, Verkhratsky A. Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. J Neurosci 25 9 — Melanin-concentrating hormone acutely stimulates feeding, but chronic administration has no effect on body weight.

Endocrinology 1 —5. Pérez CA, Stanley SA, Wysocki RW, Havranova J, Ahrens-Nicklas R, Onyimba F, et al. Molecular annotation of integrative feeding neural circuits. Cell Metab 13 2 — Domingos AI, Sordillo A, Dietrich MO, Liu ZW, Tellez LA, Vaynshteyn J, et al. Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar.

Elife 2:e Chung S, Hopf FW, Nagasaki H, Li CY, Belluzzi JD, Bonci A, et al. The melanin-concentrating hormone system modulates cocaine reward. Proc Natl Acad Sci U S A 16 —7. Georgescu D, Sears RM, Hommel JD, Barrot M, Bolaños CA, Marsh DJ, et al.

The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance. J Neurosci 25 11 — Sears RM, Liu RJ, Narayanan NS, Sharf R, Yeckel MF, Laubach M, et al.

Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone. J Neurosci 30 24 — Lopez CA, Guesdon B, Baraboi E-D, Roffarello BM, Hétu M, Richard D. Involvement of the opioid system in the orexigenic and hedonic effects of melanin-concentrating hormone.

Am J Physiol Regul Integr Comp Physiol 4 :R— Cheung GW, Kokorovic A, Lam CK, Chari M, Lam TK. Intestinal cholecystokinin controls glucose production through a neuronal network. Cell Metab 10 2 — Baggio LL, Drucker DJ.

Biology of Incretins: GLP-1 and GIP. Gastroenterology 6 — Alhadeff AL, Rupprecht LE, Hayes MR. GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake.

Endocrinology 2 — Alhadeff AL, Mergler BD, Zimmer DJ, Turner CA, Reiner DJ, Schmidt HD, et al. Endogenous glucagon-like peptide-1 receptor signaling in the nucleus tractus solitarius is required for food intake control. Neuropsychopharmacology Mietlicki-Baase EG, Ortinski PI, Rupprecht LE, Olivos DR, Alhadeff AL, Pierce RC, et al.

Am J Physiol Endocrinol Metab 11 :E— Reddy IA, Pino JA, Weikop P, Osses N, Sørensen G, Bering T, et al. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels.

Transl Psychiatry 6 5 :e Harasta AE, Power JM, von Jonquieres G, Karl T, Drucker DJ, Housley GD, et al. Septal glucagon-like peptide 1 receptor expression determines suppression of cocaine-induced behavior. Neuropsychopharmacology 40 8 — Schmidt HD, Mietlicki-Baase EG, Ige KY, Maurer JJ, Reiner DJ, Zimmer DJ, et al.

Glucagon-like peptide-1 receptor activation in the ventral tegmental area decreases the reinforcing efficacy of cocaine. Neuropsychopharmacology 41 7 — Benjannet S, Rondeau N, Day R, Chrétien M, Seidah NG. PC1 and PC2 are proprotein convertases capable of cleaving proopiomelanocortin at distinct pairs of basic residues.

Proc Natl Acad Sci U S A 88 9 —8. Xu P, Grueter BA, Britt JK, McDaniel L, Huntington PJ, Hodge R, et al. Double deletion of melanocortin 4 receptors and SAPAP3 corrects compulsive behavior and obesity in mice. Proc Natl Acad Sci U S A 26 — Burnett LC, LeDuc CA, Sulsona CR, Paull D, Rausch R, Eddiry S, et al.

Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome. J Clin Invest 1 — Zhan C, Zhou J, Feng Q, Zhang JE, Lin S, Bao J, et al. Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively.

J Neurosci 33 8 — Hentges ST, Otero-Corchon V, Pennock RL, King CM, Low MJ. Proopiomelanocortin expression in both GABA and glutamate neurons.

J Neurosci 29 43 — Li YQ, Shrestha Y, Pandey M, et al. J Clin Invest 1 —9. Rediger A, Piechowski CL, Habegger K, Grüters A, Krude H, Tschöp MH, et al.

Neuroendocrinology 95 4 — Agosti F, Cordisco Gonzalez S, Martinez Damonte V, Tolosa MJ, Di Siervi N, Schioth HB, et al.