Adan lab

Neural circuits underlying eating disorders

My team’s main focus is on identifying and targeting the neural circuits that underlie eating disorders. We use human genetics and scRNAseq data to identify cells that are underlying the processes that contribute to development of eating disorders. Viral vector tracers, optogenetics and electrophysiology are used to map neural circuits, calcium imaging (fiber photometry) is used to assess neuronal activity in awake animals and chemogenetics and pharmacology is used to unravel how specific neural circuits are implicated in regulating behaviors associated with eating disorders such as food reward seeking, feeding and hyperlocomotion.

Confocal images from a VTA section of dopaminergic neurons (green) and Leptin receptor expressing neurons (red)

The modulatory effect of leptin on the mesolimbic DA system
 

Prof. dr. Roger Adan

My main position is in the department of Translational Neuroscience, UMC Utrecht Brain Center. I am also a scientific advisor at Rintveld Eating disorder clinic, Altrecht, Zeist, guest professor at the department of Neuroscience and Physiology of Sahlgrenska Academy of the University of Gothenburg, and expert at EFSA’s working group “Added Sugars”.
My research focus is on deconstructing the mechanisms underlying eating behaviour, since this is a natural behaviour ideally suited to dissecting the neural circuits that underlie decision-making, anxiety, impulsivity and reward seeking. I am devoted to unravel mechanisms underlying eating disorders. Besides understanding what circuits underlie obesity, the main topic is to unravel the neurocircuitry that underlies Anorexia Nervosa.

 

Group members

Bart Lodder – PhD student supervised by Prof. Bernardo Sabatini, located at Harvard Medical school
My research aims to understand the heterogeneity of dopamine signaling in the nucleus accumbens and dorsal striatum, through development and implementation of novel optical methods like tapered photometry and Fluorescent lifetime photometry.

Dopamine, Nucleus accumbens, Dorsal striatum, Tapered photometry, Fluorescent lifetime photometry
Eileen Brouwer – PhD student
My research project aims to unravel neuronal alterations in Anorexia Nervosa using the activity-based anorexia mouse model.

Activity-based anorexia model, immunocytochemistry, scRNAseq
Fabien Ducrocq – Postdoc
My research aim at identifying neuronal populations that drive symptoms such as decreased feeding and hyperactivity linked to the development of Anorexia Nervosa in a laboratory mouse model.

Slice electrophysiology, Anorexia Nervosa mouse model, Reward processing

Iris Stoltenborg – PhD student
I’m conducting my research at Gothenburg University in Sweden, where Roger A. H. Adan is a guest professor. The aim of my research project in the lab of Suzanne Dickson (under the supervision of Roger) is to target and further unravel which neurons and pathways are engaged by orexigenic stimuli such as the hunger hormone ghrelin and food cues.

Transgenic mouse models, RNAscope, DREADDs
I.G. Wolterink-Donselaar
Research-technician for practical assistance of PhD-students and Postdocs in their scientific careers.

Karlijn Kooij – PhD candidate
My research aim is to unravel how the gut-brain axis – influences reward processing. I mainly focus on gut hormones and the (anorectic) microbiome. Additionally, I investigate whether a pharmacological intervention improves the outcome in an animal model for anorexia nervosa.

Fiber photometry, gut-brain axis, microbiome transplantation, anorexia rodent model

Lisa Drost – research technician
I have diverse tasks in the Adan group, which are:
Performing behavioral experiment, doing surgeries and assisting PhD and Postdocs within their research.

Behavioral tasks, Anorexia Nervosa mouse/rat model, stereotaxic surgery, practical support

Mieneke Luijendijk – animal facility manager
My role in the Adan group is very diverse. Among my tasks are; planning of experiments, performing experiments, do surgery, keep track of animal administration and assist PhDs and Post Docs with project proposals, work protocols and experiments.

Stereotactic surgery, Behavioral tasks, Anorexia Nervosa mouse model all in rats and mice

 

Recent papers

  1. Omrani A, de Vrind VAJ, Lodder B, Stoltenborg I, Kooij K, Wolterink-Donselaar IG, Luijendijk-Berg MCM, Garner KM, Van’t Sant LJ, Rozeboom A, Dickson SL, Meye FJ, Adan RAH. Identification of Novel Neurocircuitry Through Which Leptin Targets Multiple Inputs to the Dopamine System to Reduce Food Reward Seeking. Biol Psychiatry. 2021 Feb 23:S0006-3223(21)00121-9. doi: 10.1016/j.biopsych.2021.02.017. Epub ahead of print. PMID: 33867112.
  2. Flores-Dourojeanni JP, van Rijt C, Vanden Munkhof MH, Boekhoudt L, Luijendijk MCM, Vanderschuren LJMJ, Adan RAH. Temporally specific roles of ventral tegmental area projections to the nucleus accumbens and prefrontal cortex in attention and impulse control. J Neurosci. 2021 Apr 7:JN-RM-0477-20. doi: 10.1523/JNEUROSCI.0477-20.2020. Epub ahead of print. PMID: 33837050.
  3. Yeo GSH, Chao DHM, Siegert AM, Koerperich ZM, Ericson MD, Simonds SE, Larson CM, Luquet S, Clarke I, Sharma S, Clément K, Cowley MA, Haskell-Luevano C, Van Der Ploeg L, Adan RAH. The melanocortin pathway and energy homeostasis: From discovery to obesity therapy. Mol Metab. 2021 Mar 6;48:101206. doi: 10.1016/j.molmet.2021.101206. Epub ahead of print. PMID: 33684608.
  4. Adan RAH, van der Beek EM, Buitelaar JK, Cryan JF, Hebebrand J, Higgs S, Schellekens H, Dickson SL. Nutritional psychiatry: Towards improving mental health by what you eat. Eur Neuropsychopharmacol. 2019 Dec;29(12):1321-1332. doi: 10.1016/j.euroneuro.2019.10.011. Epub 2019 Nov 14. PMID: 31735529.
  5. Watson HJ, Yilmaz Z, Thornton LM, Hübel C, Coleman JRI, Gaspar HA, Bryois J, Hinney A, Leppä VM, Mattheisen M, Medland SE, Ripke S, Yao S, Giusti-Rodríguez P; Anorexia Nervosa Genetics Initiative, Hanscombe KB, Purves KL; Eating Disorders Working Group of the Psychiatric Genomics Consortium, Adan RAH, Alfredsson L, Ando T, Andreassen OA, Baker JH, Berrettini WH, Boehm I, Boni C, Perica VB, Buehren K, Burghardt R, Cassina M, Cichon S, Clementi M, Cone RD, Courtet P, Crow S, Crowley JJ, Danner UN, Davis OSP, de Zwaan M, Dedoussis G, Degortes D, DeSocio JE, Dick DM, Dikeos D, Dina C, Dmitrzak-Weglarz M, Docampo E, Duncan LE, Egberts K, Ehrlich S, Escaramís G, Esko T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fichter MM, Fischer K, Föcker M, Foretova L, Forstner AJ, Forzan M, Franklin CS, Gallinger S, Giegling I, Giuranna J, Gonidakis F, Gorwood P, Mayora MG, Guillaume S, Guo Y, Hakonarson H, Hatzikotoulas K, Hauser J, Hebebrand J, Helder SG, Herms S, Herpertz-Dahlmann B, Herzog W, Huckins LM, Hudson JI, Imgart H, Inoko H, Janout V, Jiménez-Murcia S, Julià A, Kalsi G, Kaminská D, Kaprio J, Karhunen L, Karwautz A, Kas MJH, Kennedy JL, Keski-Rahkonen A, Kiezebrink K, Kim YR, Klareskog L, Klump KL, Knudsen GPS, La Via MC, Le Hellard S, Levitan RD, Li D, Lilenfeld L, Lin BD, Lissowska J, Luykx J, Magistretti PJ, Maj M, Mannik K, Marsal S, Marshall CR, Mattingsdal M, McDevitt S, McGuffin P, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Monteleone AM, Monteleone P, Munn-Chernoff MA, Nacmias B, Navratilova M, Ntalla I, O’Toole JK, Ophoff RA, Padyukov L, Palotie A, Pantel J, Papezova H, Pinto D, Rabionet R, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ritschel F, Roberts M, Rotondo A, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer SW, Schmidt U, Schork NJ, Schosser A, Seitz J, Slachtova L, Slagboom PE, Slof-Op ‘t Landt MCT, Slopien A, Sorbi S, Świątkowska B, Szatkiewicz JP, Tachmazidou I, Tenconi E, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg AA, van Furth EF, Wagner G, Walton E, Widen E, Zeggini E, Zerwas S, Zipfel S, Bergen AW, Boden JM, Brandt H, Crawford S, Halmi KA, Horwood LJ, Johnson C, Kaplan AS, Kaye WH, Mitchell JE, Olsen CM, Pearson JF, Pedersen NL, Strober M, Werge T, Whiteman DC, Woodside DB, Stuber GD, Gordon S, Grove J, Henders AK, Juréus A, Kirk KM, Larsen JT, Parker R, Petersen L, Jordan J, Kennedy M, Montgomery GW, Wade TD, Birgegård A, Lichtenstein P, Norring C, Landén M, Martin NG, Mortensen PB, Sullivan PF, Breen G, Bulik CM. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nat Genet. 2019 Aug;51(8):1207-1214. doi: 10.1038/s41588-019-0439-2. Epub 2019 Jul 15. PMID: 31308545; PMCID: PMC6779477.
  6. Verharen JPH, van den Heuvel MW, Luijendijk M, Vanderschuren LJMJ, Adan RAH. Corticolimbic Mechanisms of Behavioral Inhibition under Threat of Punishment. J Neurosci. 2019 May 29;39(22):4353-4364. doi: 10.1523/JNEUROSCI.2814-18.2019. Epub 2019 Mar 22. PMID: 30902868; PMCID: PMC6538860.
  7. Verharen JPH, de Jong JW, Roelofs TJM, Huffels CFM, van Zessen R, Luijendijk MCM, Hamelink R, Willuhn I, den Ouden HEM, van der Plasse G, Adan RAH, Vanderschuren LJMJ. A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states. Nat Commun. 2018 Feb 21;9(1):731. doi: 10.1038/s41467-018-03087-1. PMID: 29467419; PMCID: PMC5821846.
  8. van der Plasse G, van Zessen R, Luijendijk MC, Erkan H, Stuber GD, Ramakers GM, Adan RA. Modulation of cue-induced firing of ventral tegmental area dopamine neurons by leptin and ghrelin. Int J Obes (Lond). 2015 Dec;39(12):1742-9. doi: 10.1038/ijo.2015.131. Epub 2015 Jul 17. PMID: 26183405; PMCID: PMC4722241.
  9. Adan RA. Mechanisms underlying current and future anti-obesity drugs. Trends Neurosci. 2013 Feb;36(2):133-40. doi:10.1016/j.tins.2012.12.001. Epub 2013 Jan 8. PMID: 23312373.
  10. Meye FJ, Trezza V, Vanderschuren LJ, Ramakers GM, Adan RA. Neutral antagonism at the cannabinoid 1 receptor: a safer treatment for obesity. Mol Psychiatry. 2013 Dec;18(12):1294-301. doi: 10.1038/mp.2012.145. Epub 2012 Oct 16. PMID: 23070073.