A1 - Targeting neurobehavioral determinants of obesity

Based on the current funding period results, we propose novel pathomechanistic links between visceral fat, low-grade inflammation, and changes in brain structure and function in obesity, which in turn relate to differences in cognition. Analyses further indicate that the gut microbiota modulates eating behavior via short-chain fatty acids signaling. Our goal is to now translate these findings into novel obesity-treatment options that target body-brain communication. To this end, we plan to test the effects of a pre-biotic intervention over 26 weeks compared to a placebo on food decision-making in a randomized controlled trial with 60 obese patients. Mechanistic insights will be gained through the integration of task-based fMRI, microbiota sequencing and metabolomics.

Figure 1: Brain connectivity between hubs of the reward network (left panel) and relation of obesity-genetic risk alleles to body mass index (BMI, right panel). Beyer F et al., Int J Obese 2020. Individual data points are shown for carriers of 0, 1 or 2 FTO risk alleles (x-axis) with no or at least one Taq1A risk allele (red/blue, respectively). n = 378, FA fractional anisotropy, OFC, orbitofrontal cortex; L, left hemisphere; R, right hemisphere.
Fig. 2: Model of (un)healthy brain-body interactions in obesity. Increased value of high-caloric food (A) leads to weight gain, which in turn affects brain and behavior through dysbalanced systemic communication (unfavorable signal, in red). Targeting the brain through modulation of the gut with prebiotics (B) may lead to better food choices (in green, favorable signal). Potential mechanisms (C) involve energy metabolism, microbiota, inflammation and the sympathetic nervous system.
Würfel M, Breitfeld J, Gebhard C, Scholz M, Baber R, Riedel-Heller SG, Blüher M, Stumvoll M, Kovacs P, Tönjes A. Interplay between adipose tissue secreted proteins, eating behavior and obesity. Eur J Nutr. 2021 Oct 12.

Weiner J, Roth L, Kranz M, Brust P, Boelen A, Klöting N, Heiker JT, Blüher M, Tönjes A, Pfluger PT, Stumvoll M, Mittag J, Krause K. Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels. Mol Metab. 2021 Oct 2:101348. 

Hoffmann A, Ebert T, Hankir MK, Flehmig G, Klöting N, Jessnitzer B, Lössner U, Stumvoll M, Blüher M, Fasshauer M, Tönjes A, Miehle K, Kralisch S. Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice. Nutrients. 2021 Jul 22;13(8):2499.

Heinrichs HS, Beyer F, Medawar E, Prehn K, Ordemann J, Flöel A, Witte AV. Effects of bariatric surgery on functional connectivity of the reward and default mode network: A pre-registered analysis. Hum Brain Mapp . 2021 Aug 25.

Chakaroun RM, Massier L, Heintz-Buschart A, Said N, Fallmann J, Crane A, Schütz T, Dietrich A, Blüher M, Stumvoll M, Musat N, Kovacs P. Circulating bacterial signature is linked to metabolic disease and shifts with metabolic alleviation after bariatric surgery. Genome Med. 2021 Jun 22;13(1):105.

Chen J, … Kiess W, … Körner A, Kovacs P,…, Stumvoll M, …Tönjes A,... , Barroso I. The trans-ancestral genomic architecture of glycemic traits. Nat Genet. 2021 Jun;53(6):840-860.

Epperlein S, Gebhardt C, Rohde K, Chakaroun R, Patt M, Schamarek I, Kralisch S, Heiker JT, Scholz M, Stumvoll M, Kovacs P, Breitfeld J, Tönjes A. The Effect of FGF21 and Its Genetic Variants on Food and Drug Cravings, Adipokines and Metabolic Traits. Biomedicines. 2021 Mar 29;9(4):345.

Yaskolka Meir A, Keller M, Bernhart SH, Rinott E, Tsaban G, Zelicha H, Kaplan A, Schwarzfuchs D, Shelef I, Gepner Y, Li J, Lin Y, Blüher M, Ceglarek U, Stumvoll M, Stadler PF, Stampfer MJ, Kovacs P, Liang L, Shai I. Lifestyle weight-loss intervention may attenuate methylation aging: the CENTRAL MRI randomized controlled trial. Clin Epigenetics. 2021 Mar 4;13(1):48.

Yaskolka Meir A, Rinott E, Tsaban G, Zelicha H, Kaplan A, Rosen P, Shelef I, Youngster I, Shalev A, Blüher M, Ceglarek U, Stumvoll M, Tuohy K, Diotallevi C, Vrhovsek U, Hu F, Stampfer M, Shai I. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial. Gut. 2021 Jan 18:gutjnl-2020-323106.

 Rinott E, Youngster I, Yaskolka Meir A, Tsaban G, Zelicha H, Kaplan A, Knights D, Tuohy K, Fava F, Scholz MU, Ziv O, Reuven E, Tirosh A, Rudich A, Blüher M, Stumvoll M, Ceglarek U, Clement K, Koren O, Wang DD, Hu FB, Stampfer MJ, Shai I. Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain. Gastroenterology. 2021 Jan;160(1):158-173.e10.

Molinaro A, Bel Lassen P, Henricsson M, Wu H, Adriouch S, Belda E, Chakaroun R, Nielsen T, Bergh PO, Rouault C, André S, Marquet F, Andreelli F, Salem JE, Assmann K, Bastard JP, Forslund S, Le Chatelier E, Falony G, Pons N, Prifti E, Quinquis B, Roume H, Vieira-Silva S, Hansen TH, Pedersen HK, Lewinter C, Sønderskov NB; MetaCardis Consortium, Køber L, Vestergaard H, Hansen T, Zucker JD, Galan P, Dumas ME, Raes J, Oppert JM, Letunic I, Nielsen J, Bork P, Ehrlich SD, Stumvoll M, Pedersen O, Aron-Wisnewsky J, Clément K, Bäckhed F. Author Correction: Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology. Nat Commun. 2020 Dec 21;11(1):6448.

Esefeld K, Kress S, Behrens M, Zimmer P, Stumvoll M, Thurm U, Gehr B, Brinkmann C, Halle M. Diabetes, Sports and Exercise. Exp Clin Endocrinol Diabetes. 2020 Dec 21.

Poessel M, Breuer N, Joshi A, Pampel A, Villringer A, Hummel T, Horstman A. Reduced Olfactory Bulb Volume in Obesity and Its Relation to Metabolic Health Status. Front. Hum. Neurosci. 2020 Nov 27;14:586998.

Beyer F, Zhang R, Scholz M, Wirkner K, Loeffler M, Stumvoll M, Villringer A, Witte AV. Higher BMI, but not obesity-related genetic polymorphisms, correlates with lower structural connectivity of the reward network in a population-based study. Int J Obes (Lond). 2020 Oct 25.

Kynast J, Quinque EM, Polyakova M, Luck T, Riedel-Heller SG, Baron-Cohen S, Hinz A, Witte AV, Sacher J, Villringer A, Schroeter ML. Mindreading From the Eyes Declines With Aging - Evidence From 1,603 Subjects. Front Aging Neurosci. 2020 Oct 22;12:550416.

Landgraf K, Klöting N, Gericke M, Maixner N, Guiu-Jurado E, Scholz M, Witte AV, Beyer F, Schwartze JT, Lacher M, Villringer A, Kovacs P, Rudich A, Blüher M, Kiess W, Körner A.The Obesity-Susceptibility Gene TMEM18 Promotes Adipogenesis through Activation of PPARG.Cell Rep. 2020 Oct 20;33(3):108295.

Poessel M, Freiherr J, Wiencke K, Villringer A, Horstmann A. Insulin Resistance Is Associated with Reduced Food Odor Sensitivity across a Wide Range of Body Weights. Nutrients. 2020 Jul 24;12(8):E2201

Schleinitz D, Krause K, Wohland T, Gebhardt C, Linder N, Stumvoll M, Blüher M, Bechmann I, Kovacs P, Gericke M, Tönjes A. Identification of distinct transcriptome signatures of human adipose tissue from fifteen depots. Eur J Hum Genet. 2020 Jul 13.

Keller M, Gebhardt C, Huth S, Schleinitz D, Heyne H, Scholz M, Stumvoll M, Böttcher Y, Tönjes A, Kovacs P. Genetically programmed changes in transcription of the novel progranulin regulator. J Mol Med (Berl) . 2020 Jul 3

Vieira-Silva S, Falony G, Belda E, Nielsen T, Aron-Wisnewsky J, Chakaroun R, Forslund SK, Assmann K, Valles-Colomer M, Nguyen TTD, Proost S, Prifti E, Tremaroli V, Pons N, Le Chatelier E, Andreelli F, Bastard JP, Coelho LP, Galleron N, Hansen TH, Hulot JS, Lewinter C, Pedersen HK, Quinquis B, Rouault C, Roume H, Salem JE, Søndertoft NB, Touch S; MetaCardis Consortium, Dumas ME, Ehrlich SD, Galan P, Gøtze JP, Hansen T, Holst JJ, Køber L, Letunic I, Nielsen J, Oppert JM, Stumvoll M, Vestergaard H, Zucker JD, Bork P, Pedersen O, Bäckhed F, Clément K, Raes J. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis. Nature. 2020 May;581(7808):310-315. 

Medawar E, Enzenbach C, Roehr S, Villringer A, Riedel-Heller SG, Witte AV. Less Animal-based Food, Better Weight Status: Associations of the Restriction of Animal-Based Product Intake With Body-Mass-Index, Drepressive Symptoms and Personality in the Gerneral Population. Nutrients. 2020 May 20; 12(5):E1492.

Al E, Iliopoulos F, Forschack N, Nierhaus T, Grund M, Motyka P, Gaebler M, Nikulin VV, Villringer A. Heart–brain interactions shape somatosensory perception and evoked potentials. Proc Natl Acad Sci U S A. 2020 Apr 27. pii: 201915629.

Beyer F, Prehn K, Wüsten KA, Villringer A, Ordemann J, Flöel A, Witte AV. Weight loss reduces head motion: Revisiting a major confound in neuroimaging. Hum Brain Mapp. 2020 Apr 2.

Breitfeld J, Kehr S, Müller L, Stadler PF, Böttcher Y, Blüher M, Stumvoll M, Kovacs P. Developmentally Driven Changes in Adipogenesis in Different Fat Depots Are Related to Obesity. Front Endocrinol (Lausanne). 2020 Mar 26;11:138.

Kube J, Wiencke K, Hahn S, Villringer A, Neumann J. Enhanced Go and NoGo Learning in Individuals With Obesity. Front Behav Neurosci. 2020 Feb 14;14:15.

Abshagen K, Berger C, Dietrich A, Schütz T, Wittekind C, Stumvoll M, Blüher M, Klöting N. A Human REPIN1 Gene Variant: Genetic Risk Factor for the Development of Nonalcoholic Fatty Liver Disease. Clin Transl Gastroenterol. 2020 Jan;11(1):e00114.

Klöting N, Kern M, Moruzzi M, Stumvoll M, Blüher M. Tamoxifen treatment causes early hepatic insulin resistance. Acta Diabetol. 2020 Jan 6.

Morys F, Janssen LK, Cesnaite E, Beyer F, Garcia-Garcia I, Kube J, Kumral D, Liem F, Mehl N, Mahjoory K, Schrimpf A, Gaebler M, Margulies D, Villringer A, Neumann J, Nikulin V, Horstmann A. Hemispheric asymmetries in resting-state EEG and fMRI are related to approach and avoidance behaviour, but not to eating behaviour or BMI. Hum Brain Mapp. 2019 Nov 21.

García-García I, Kube J, Morys F, Schrimpf A, Kanaan AS, Gaebler M, Villringer A, Dagher A, Horstmann A, Neumann J. Liking and left amygdala activity during food versus non-food processing are modulated by emotional context. Cogn Affect Behav Neurosci. 2019 Nov 11.

Thomas K, Beyer F, Lewe G, Zhang R, Schindler S, Schönknecht P, Stumvoll M, Villringer A, Witte AV. Higher body mass index is linked to altered hypothalamic microstructure. Sci Rep. 2019 Nov 22;9(1):17373.

Beuchel C, Becker S, Dittrich J, Kirsten H, Toenjes A, Stumvoll M, Loeffler M, Thiele H, Beutner F, Thiery J, Ceglarek U, Scholz M., Clinical and lifestyle related factors influencing whole blood metabolite levels - A comparative analysis of three large cohorts. Mol Metab. 2019 Nov;29:76-85.

Satizabal C., [...], Witte AV, [...], Villringer A, [...], Seshadri S., Genetic Architecture of Subcortical Brain Structures in 38,851 Individuals., Nat Genet. 2019 Oct 21. Epub ahead of print

Medawar E, Huhn S, Villringer A, Witte A., The effects of plant-based diets on the body and the brain: a systematic Review., Transl Psychiatry. 2019 Sep 12;9(1):226.

Teumer A, [...], Körner A, Kovacs P, [...], Stumvoll M, [...], Köttgen A. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria. Nat Commun. 2019 Sep 11;10(1):4130.

Beyer F, Kharabian Masouleh S, Kratzsch J, Schroeter ML, Röhr S, Riedel-Heller SG, Villringer A, Witte AV. A Metabolic Obesity Profile Is Associated With Decreased Gray Matter Volume in Cognitively Healthy Older Adults. Front Aging Neurosci. 2019 Aug 2;11:202.

Weingarten MFJ, Scholz M, Wohland T, Horn K, Stumvoll M, Kovacs P, Tönjes A. Circulating oxytocin is genetically determined and associated with obesity and impaired glucose tolerance. J Clin Endocrinol Metab. 2019 Jul 30. pii: jc.2019-00643

Zelicha H, Kaplan A, Yaskolka Meir A, Tsaban G, Rinott E, Shelef I, Tirosh A, Brikner D, Pupkin E, Qi L, Thiery J, Stumvoll M, Kloting N, von Bergen M, Ceglarek U, Blüher M, Stampfer MJ, Shai I. The Effect of Wolffia globosa Mankai, a Green Aquatic Plant, on Postprandial Glycemic Response: A Randomized Crossover Controlled Trial. Diabetes Care. 2019 Jul;42(7):1162-1169

Heinitz S, Gebhardt C, Piaggi P, Krüger J, Heyne H, Weiner J, Heiker JT, Stumvoll M, Blüher M, Baier L, Rudich A, Kovacs P, Tönjes A. Atg7-knockdown reduces chemerin secretion in murine adipocytes. J Clin Endocrinol Metab. 2019 Jun 21. pii: jc.2018-01980.

Wuttke M,[...], Kiess W, Kleber M, Koenig W, Kooner JS, Körner A, Kovacs P,[...], Stumvoll M., Pattaro C. A catalog of genetic loci associated with kidney function from analyses of a million individuals. Nat Genet. 2019 Jun;51(6):957-972.

Satizabal C., [...], Witte AV, [...], Villringer A, [...], Seshadri S., Genetic Architecture of Subcortical Brain Structures in 38,851 Individuals., Nat Genet. 2019 Oct 21. Epub ahead of print

Medawar E, Huhn S, Villringer A, Witte A., The effects of plant-based diets on the body and the brain: a systematic Review., Transl Psychiatry. 2019 Sep 12;9(1):226.

Beyer F, Kharabian Masouleh S, Kratzsch J, Schroeter ML, Röhr S, Riedel-Heller SG, Villringer A, Witte AV. A Metabolic Obesity Profile Is Associated With Decreased Gray Matter Volume in Cognitively Healthy Older Adults. Front Aging Neurosci. 2019 Aug 2;11:202.

Zsido RG, Heinrich M, Slavich GM, Beyer F, Kharabian Masouleh S, Kratzsch J, Raschpichler M, Mueller K, Scharrer U, Löffler M, Schroeter ML, Stumvoll M, Villringer A, Witte AV, Sacher J. Association of Estradiol and Visceral Fat With Structural Brain Networks and Memory Performance in Adults. JAMA Netw Open. 2019 Jun 5;2(6):e196126.

van den Heuvel MP, Scholtens LH, van der Burgh HK, Agosta F, Alloza C, Arango C, Auyeung B, Baron-Cohen S, Basaia S, Benders MJNL, Beyer F, Booij L, Braun KPJ, Filho GB, Cahn W, Cannon DM, Chaim-Avancini TM, Chan SSM, Chen EYH, Crespo-Facorro B, Crone EA, Dannlowski U, de Zwarte SMC, Dietsche B, Donohoe G, Plessis SD, Durston S, Díaz-Caneja CM, Díaz-Zuluaga AM, Emsley R, Filippi M, Frodl T, Gorges M, Graff B, Grotegerd D, Gąsecki D, Hall JM, Holleran L, Holt R, Hopman HJ, Jansen A, Janssen J, Jodzio K, Jäncke L, Kaleda VG, Kassubek J, Masouleh SK, Kircher T, Koevoets MGJC, Kostic VS, Krug A, Lawrie SM, Lebedeva IS, Lee EHM, Lett TA, Lewis SJG, Liem F, Lombardo MV, Lopez-Jaramillo C, Margulies DS, Markett S, Marques P, Martínez-Zalacaín I, McDonald C, McIntosh AM, McPhilemy G, Meinert SL, Menchón JM, Montag C, Moreira PS, Morgado P, Mothersill DO, Mérillat S, Müller HP, Nabulsi L, Najt P, Narkiewicz K, Naumczyk P, Oranje B, Ortiz-Garcia de la Foz V, Peper JS, Pineda JA, Rasser PE, Redlich R, Repple J, Reuter M, Rosa PGP, Ruigrok ANV, Sabisz A, Schall U, Seedat S, Serpa MH, Skouras S, Soriano-Mas C, Sousa N, Szurowska E, Tomyshev AS, Tordesillas-Gutierrez D, Valk SL, van den Berg LH, van Erp TGM, van Haren NEM, van Leeuwen JMC, Villringer A, Vinkers CH, Vollmar C, Waller L, Walter H, Whalley HC, Witkowska M, Witte AV, Zanetti MV, Zhang R, de Lange SC. 10Kin1day: A Bottom-Up Neuroimaging Initiative. Front Neurol. 2019 May 9;10:425.

Warrington NM, [...], Kovacs P, [...], Tönjes A, Stumvoll M, Michaelsen KF, Eloranta AM, Lakka TA, van Duijn CM, Kiess W, Körner A, [...], Freathy RM. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nat Genet. 2019 May;51(5):804-814.

Rohde K, Keller M, la Cour Poulsen L, Rønningen T, Stumvoll M, Tönjes A, Kovacs P, Horstmann A, Villringer A, Blüher M, Böttcher Y. (Epi)genetic regulation of CRTC1 in human eating behaviour and fat Distribution. EBioMedicine. 2019 May 29. pii: S2352-3964(19)30358-5.

Beyer F, García-García I, Heinrich M, Schroeter ML, Sacher J, Luck T, Riedel-Heller SG, Stumvoll M, Villringer A, Witte AV. Neuroanatomical correlates of food addiction symptoms and body mass index in the general population. Hum Brain Mapp. 2019 Feb 28.

Lampe L, Zhang R, Beyer F, Huhn S, Kharabian Masouleh S, Preusser S, Bazin PL, Schroeter ML, Villringer A, Witte AV. Visceral obesity relates to deep white matter hyperintensities via inflammation. Ann Neurol. 2019 Feb;85(2):194-203.

Püschel J, Miehle K, Müller K, Villringer AStumvoll M, Fasshauer M, Schlögl H. Beneficial effects of leptin substitution on impaired eating behavior in lipodystrophy are sustained beyond 150 weeks of treatment. Cytokine. 2019 Jan;113:400-404.

Vojinovic D, Adams HH, Jian X, Yang Q, Smith AV, Bis JC, Teumer A, Scholz M, Armstrong NJ, Hofer E, Saba Y, Luciano M, Bernard M, Trompet S, Yang J, Gillespie NA, van der Lee SJ, Neumann A, Ahmad S, Andreassen OA, Ames D, Amin N, Arfanakis K, Bastin ME, Becker DM, Beiser AS, Beyer F, Brodaty H, Bryan RN, Bülow R, Dale AM, De Jager PL, Deary IJ, DeCarli C, Fleischman DA, Gottesman RF, van der Grond J, Gudnason V, Harris TB, Homuth G, Knopman DS, Kwok JB, Lewis CE, Li S, Loeffler M, Lopez OL, Maillard P, El Marroun H, Mather KA, Mosley TH, Muetzel RL, Nauck M, Nyquist PA, Panizzon MS, Pausova Z, Psaty BM, Rice K, Rotter JI, Royle N, Satizabal CL, Schmidt R, Schofield PR, Schreiner PJ, Sidney S, Stott DJ, Thalamuthu A, Uitterlinden AG, Valdés Hernández MC, Vernooij MW, Wen W, White T, Witte AV, Wittfeld K, Wright MJ, Yanek LR, Tiemeier H, Kremen WS, Bennett DA, Jukema JW, Paus T, Wardlaw JM, Schmidt H, Sachdev PS, Villringer A, Grabe HJ, Longstreth WT, van Duijn CM, Launer LJ, Seshadri S, Ikram MA, Fornage M. Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume.Nat Commun. 2018 Nov 23;9(1):4960.

Hardikar S, Wallroth R, Villringer A, Ohla K. Shorter-lived neural taste representations in obese compared to lean individuals. Sci Rep. 2018 Jul 23;8(1):11027.

Huhn S, Beyer F, Zhang R, Lampe L, Grothe J, Kratzsch J, Willenberg A, Breitfeld J, Kovacs P, Stumvoll M, Trampel R, Bazin PL, Villringer A, Witte AV. Effects of resveratrol on glucose, memory and the hippocampus - a randomized controlled trial. Neuroimage. 2018 Mar 13;174:177-190.

Zhang R, Beyer F, Lampe L, Luck T, Riedel-Heller SG, Loeffler M, Schroeter ML, Stumvoll MVillringer A, Witte AV. White matter microstructural variability mediates the relation between obesity and cognition in healthy adults.Neuroimage. 2018 Feb 2;172:239-249

Schwarz C, Wirth M, Gerischer L, Grittner U, Witte AV, Köbe T, Flöel A. Effects of Omega-3 Fatty Acids on Resting Cerebral Perfusion in Patients with Mild Cognitive Impairment: A Randomized Controlled Trial. J Prev Alzheimers Dis. 2018;5(1):26-30.

Hellrung L, Dietrich A, Hollmann M, Pleger B, Kalberlah C, Roggenhofer E, Villringer A, Horstmann A. Intermittent compared to continuous real-time fMRI neurofeedback boosts control over amygdala activation. NeuroImage. 2017;166:198-208.

Rodriguez FS, Schroeter ML, Arélin K, Witte AV, Baber R, Burkhardt R, Engel C, Löffler M, Thiery J, Villringer A, Luck T, Riedel-Heller SG. APOE e4-genotype and lifestyle interaction on cognitive performance: Results of the LIFE-Adult-study.Health Psychol. 2018 Feb;37(2):194-205.

Tönjes A, Scholz M, Krüger J, Krause K, Schleinitz D, Kirsten H, Gebhardt C, Marzi C, Grallert H, Ladenvall C, Heyne H, Laurila E, Kriebel J, Meisinger C, Rathmann W, Gieger C, Groop L, Prokopenko I, Isomaa B, Beutner F, Kratzsch J, Fischer-Rosinsky A, Pfeiffer A, Krohn K, Spranger J, Thiery J, Blüher M, Stumvoll M, Kovacs P. Genome wide meta-analysis identifies novel determinants of circulating serum progranulin. Hum Mol Genet. 2018 Feb 1;27(3):546-558.

Huhn S, Beyer F, Zhang R, Lampe L, Grothe J, Kratzsch J, Willenberg A, Breitfeld J, Kovacs P, Stumvoll M, Trampel R, Bazin PL, Villringer A, Witte AV. Effects of resveratrol on memory performance, hippocampus connectivity and microstructure in older adults - A randomized controlled trial. Neuroimage. 2018 Mar 13;174:177-190.

Ebert T, Gebhardt C, Scholz M, Wohland T, Schleinitz D, Fasshauer M, Blüher M, Stumvoll M, Kovacs P, Tönjes A. Relationship between twelve adipocytokines and distinct components of the metabolic syndrome. JClinEndocrinol Metab. 2018: 10.1210/jc.2017-02085 

Gepner Y, Shelef I, Schwarzfuchs D, Cohen N, Bril N, Rein M, Tsaban G, Zelicha H, Yaskolka Meir A, Tene L, Sarusy B, Rosen P, Hoffman JR, Stout JR, Thiery J, Ceglarek U, Stumvoll M, Blüher M, Stampfer MJ, Shai I. Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub-study of the CENTRAL trial. PLoS One. 2017;12:e0188431.

Gepner Y, Shelef I, Schwarzfuchs D, Zelicha H, Tene L, Yaskolka Meir A, Tsaban G, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Komy O, Wolak A, Chassidim Y, Golan R, Avni-Hassid H, Bilitzky A, Sarusi B, Goshen E, Shemesh E, Henkin Y, Stumvoll M, Blüher M, Thiery J, Ceglarek U, Rudich A, Stampfer MJ, Shai I. Effect of distinct lifestyle interventions on mobilization of fast storage pools: the CENTRAL MRI randomized control trial. Circulation. 2017; Epub ahead of print.

Kastner L, Kube J, Villringer A, Neumann J. Cardiac concomitants of feedback and prediction error processing in reinforcement learning. Front Neurosci. 2017;11:598.

Hellrung L, Dietrich A, Hollmann M, Pleger B, Kalberlah C, Roggenhofer E, Villringer A, Horstmann A. Intermittent compared to continuous real-time fMRI neurofeedbak boosts control over amygdala activation. NeuroImage. 2017;166:198-208.

Kharabian Masouleh S, Beyer F, Lampe L, Loeffler M, Luck T, Riedel-Heller SG, Schroeter ML, Stumvoll MVillringer A, Witte AV. Gray matter structural networks are associated with cardiovascular risk factors in healthy older adults. J Cereb Blood Flow Metab. 2017; Epub ahead of print.

Mathar D, Neumann J, Villringer A, Horstmann A. Failing to learn from negative prediction errors: Obesity is associated with alterations in a fundamental neural learning mechanism. Cortex. 2017;95:222-37.

Rohde K, Klös M, Hopp L, Liu X, Keller M, Stumvoll M, Dietrich A, Schön MR, Gärtner D, Lohmann T, Dreßler M, Kovacs P, Binder H, Blüher M, Böttcher Y. IRS1 DNA promoter methylation and expression in human adipose tissue are related to fat distribution and metabolic traits. Sci Rep. 2017;7:12369.

Tsaban G, Wolak A, Avni-Hassid H, Gepner Y, Shelef I, Henkin Y, Schwarzfuchs D, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Tene L, Zelicha H, Yaskolka-Meir A, Komy O, Bilitzky A, Chassidim Y, Ceglarek U, Stumvoll M, Blüher M, Thiery J, Dicker D, Rudich A, Stamper MJ, Shai I. Dynamics of intrapericardial and extrapericardial fat tissues during long-term, dietary-induced, moderate weight loss. Am J Clin Nutr. 2017;106:984-95.

Kralisch S, Hoffmann A, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M, Ebert T. The brown-fat-secreted adipokine neuregulin 4 is decreased in gestational diabetes mellitus. Diabetes Metab. 2017; Epub ahead of print.

Rodriguez FS, Schroeter ML, Witte AV, Engel C, Löffler M, Thiery J, Villringer A, Luck T, Riedel-Heller SG. Could high mental demands at work offset the adverse association between social isolation and cognitive functioning? Results of population-based LIFE-adult-study. Am J Geriatr Psychiatry. 2017;25:1258-69.

Polyakova M, Schlögl H, Sacher J, Schmidt-Kassow M, Kaiser J, Stumvoll M, Kratzsch J, Schroeter ML. Stability of BDNF in human samples stored up to 6 months and correlations of serum and EDTA-plasma concentrations. Int J Mol Sci. 2017;18:1189.

Weiner J, Rohde K, Krause K, Zieger K, Klöting N, Kralisch S, Kovacs P, Stumvoll M, Blüher M, Böttcher Y, Heiker JT. Brown adipose tissue (BAT) specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation. Mol Met. 2017; Epub ahead of print.

Keller M, Hopp L, Liu X, Wohland T, Rohde K, Cancello R, Klös M, Bacos K, Kern M, Eichelmann F, Dietrich A, Schön MR, Gärtner D, Lohmann T, Dreßler M, Stumvoll M, Kovacs P, DiBlasio AM, Ling C, Binder H, Blüher M, Böttcher Y. Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity. Mol Metab. 2016;6:86-100.

Hardikar S, Höchenberger R, Villringer A, Ohla K. Higher sensitivity to sweet and salty taste in obese compared to lean individuals. Appetite. 2017;111:158-65.

Schrimpf A, Kube J, Neumann J, Horstmann A, Villringer A, Gaebler M. Parasympathetic cardio-regulation during social interactions in individuals with obesity - The influence of negative body image. Cogn Affect Behav Neurosci. 2017;17:330-47.

Horikoshi M, Beaumont RN, Day FR, Warrington NM, Kooijman MN, Fernandez-Tajes J, Feenstra B, van Zuydam NR, Gaulton KJ, Grarup N, Bradfield JP, Strachan DP, Li-Gao R, Ahluwalia TS, Kreiner E, Rueedi R, Lyytikäinen LP, Cousminer DL, Wu Y, Thiering E, Wang CA, Have CT, Hottenga JJ, Vilor-Tejedor N, Joshi PK, Boh ET, Ntalla I, Pitkänen N, Mahajan A, van Leeuwen EM, Joro R, Lagou V, Nodzenski M, Diver LA, Zondervan KT, Bustamante M, Marques-Vidal P, Mercader JM, Bennett AJ, Rahmioglu N, Nyholt DR, Ma RC, Tam CH, Tam WH; CHARGE Consortium Hematology Working Group, Ganesh SK, van Rooij FJ, Jones SE, Loh PR, Ruth KS, Tuke MA, Tyrrell J, Wood AR, Yaghootkar H, Scholtens DM, Paternoster L, Prokopenko I, Kovacs P, Atalay M, Willems SM, Panoutsopoulou K, Wang X, Carstensen L, Geller F, Schraut KE, Murcia M, van Beijsterveldt CE, Willemsen G, Appel EV, Fonvig CE, Trier C, Tiesler CM, Standl M, Kutalik Z, Bonàs-Guarch S, Hougaard DM, Sánchez F, Torrents D, Waage J, Hollegaard MV, de Haan HG, Rosendaal FR, Medina-Gomez C, Ring SM, Hemani G, McMahon G, Robertson NR, Groves CJ, Langenberg C, Luan J, Scott RA, Zhao JH, Mentch FD, MacKenzie SM, Reynolds RM; Early Growth Genetics (EGG) Consortium, Lowe WL, Tönjes A, Stumvoll M, Lindi V, Lakka TA, van Duijn CM, Kiess W, Körner A, Sørensen TI, Niinikoski H, Pahkala K, Raitakari OT, Zeggini E, Dedoussis GV, Teo YY, Saw SM, Melbye M, Campbell H, Wilson JF, Vrijheid M, de Geus EJ, Boomsma DI, Kadarmideen HN, Holm JC, Hansen T, Sebert S, Hattersley AT, Beilin LJ, Newnham JP, Pennell CE, Heinrich J, Adair LS, Borja JB, Mohlke KL, Eriksson JG, Widén E, Kähönen M, Viikari JS, Lehtimäki T, Vollenweider P, Bønnelykke K, Bisgaard H, Mook-Kanamori DO, Hofman A, Rivadeneira F, Uitterlinden AG, Pisinger C, Pedersen O, Power C, Hyppönen E, Wareham NJ, Hakonarson H, Davies E, Walker BR, Jaddoe VW, Järvelin MR, Grant SF, Vaag AA, Lawlor DA, Frayling TM, Smith GD, Morris AP, Ong KK, Felix JF, Timpson NJ, Perry JR, Evans DM, McCarthy MI, Freathy RM. Genome-wide associations for birth weight and correlations with adult disease. Nature. 2016;538:248-52.

Guiu-Jurado E, Unthan M, Böhler N, Kern M, Landgraf K, Dietrich A, Schleinitz D, Ruschke K, Klöting N, Faßhauer M, Tönjes A, Stumvoll M, Körner A, Kovacs P, Blüher M. Bone morphogenetic protein 2 (BMP2) may contribute to partition of energy storage into visceral and subcutaneous fat depots. Obesity (Silver Spring). 2016;24:2092-100.

Garcia-Garcia I, Kube J, Gaebler M, Horstmann A, Villringer A, Neumann J. Neural processing of negative emotional stimuli and the influence of age, sex and task-related characteristics. Neurosci Biobehav Rev. 2016;68:773-93.

Grellmann C, Neumann J, Bitzer S,Kovacs P,Tönjes A, Westlye LT, Anreassen OA, Stumvoll MVillringer A, Horstmann A. Random projection for fast and efficient multivariate correlation analysis of high-dimensional data: A new approach. Front Genet. 2016;7:102.

Kharabian Masouleh S, Arelin K, Horstmann A, Lample L, Kipping JA, Luck T, Riedel-Heller SG, Schroeter ML, Stumvoll MVillringer A, Witte AV. Higher body mass index in older adults is associated with lower gray matter volume: implications for memory performance. Neurobiol Aging. 2016;40:1-10.

Köbe T, Witte AV, Schnelle A, Grittner U, Tesky VA, Pantel J, Schuchardt JP, Hahn A, Bohlken J, Rujescu D, Flöel A. Vitamin B-12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment. Am J Clin Nutr. 2016;103:1045-54.

Köbe T, Witte AV, Schnelle A, Lesemann A, Fabian S, Tesky VA, Pantel J, Flöel A. Combined omega-3 fatty acids, aerobic exercise and cognitive stimulation prevents decline in gray matter volume of the frontal, parietal and cingulate cortex in patients with mild cognitive impairment. Neuroimage. 2016;131:226-38.

Schlögl H, Horstmann A, Villringer AStumvoll M. Functional neuroimaging in obesity and the potential for development of novel treatments. Lancet Diabetes Endocrinol. 2016;4:695-705.

Huhn S, Kharabian Masouleh S, Stumvoll MVillringer A, Witte V. Components of a Mediterranean diet and their impact on cognitive funtions in aging. Front Aging Neurosci. 2015;7:132.

Mueller K, Möller HE, Horstmann A, Busse-Voigt FP, Lepsien J, Blüher M, Stumvoll MVillringer A, Pleger B. Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity. Front Hum Neurosci. 2015;9:372.

Rohde K, Federbusch M, Horstmann A, Keller M, Villringer AStumvoll M, Tönjes A, Kovacs P, Böttcher Y. Genetic variants in AKR1B10 associate with human eating behavior. BMC Genet. 2015;16:31.

Hellrung L, Hollmann M, Zscheyge O, Schlumm T, Kalberlah C, Roggenhofer E, Okon-Singer H, Villringer A, Horstmann A. Flexible adaptive paradigms for fMRI using a novel software package 'Brain Analysis in Real-Time' (BART). PLoS One. 2015;10:e0118890.

Horstmann A, Kovacs P, Kabisch S, Boettcher Y, Schloegl H, Toenjes A, Stumvoll M, Pleger B, Villringer A. Common genetic variation near MC4R has a sex-specific impact on human brain structure and brain behavior. PLoS One. 2013;8:e74362.

Schroeter ML, Vogt B, Frisch S, Becker G, Barthel H, Mueller K, Villringer A, Sabri O. Executive deficits are related to the inferior frontal junction in early dementia. Brain. 2012;135:201-15.

Horstmann A, Busse FP, Mathar D, Müller K, Lepsien J, Schlögl H, Kabisch S, Kratzsch J, Neumann J, Stumvoll MVillringer A, Pleger B. Obesity-related differences between women and men in brain structure and goal-directed behavior. Front Hum Neurosci. 2011;5:58.

Hollmann M, Hellrung L, Pleger B, Schlögl H, Kabisch S, Stumvoll MVillringer A, Horstmann A. Neural correlates of the volitional regulation of the desire for  food. Int J Obes (Lond). 2011;36:648-55.

Mueller K, Anwander A, Möller HE, Horstmann A, Lepsien J, Busse F, Mohammadi S, Schroeter ML, Stumvoll MVillringer A, Pleger B. Sex-dependent influences of obesity on cerebral white matter investigated by diffusion-tensor imaging. PLoS One. 2011;6:e18544.

Tönjes A, Zeggini E, Kovacs P, Böttcher Y, Schleinitz D, Dietrich K, Morris AP, Enigk B, Rayner NW, Koriath M, Eszlinger M, Kemppinen A, Prokopenko I, Hoffmann K, Teupser D, Thiery J, Krohn K, McCarthy MI, Stumvoll M. Association of FTO variants with BMI and fat mass in the self-contained population of Sorbs in Germany. Eur J Hum Genet. 2010;18:104-10.

Saxena R, Hivert MF, Langenberg C, Tanaka T, [69 authors], Kovacs P, [29 authors], Tönjes A, [34 authors], Stumvoll M, [16 authors], Watanabe RM. Genetic variation in gastric inhibitory polypeptide receptor (GIPR) impacts the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010;42:142-8.

Speliotes EK, Willer CJ, Berndt SI, Monda KL, [167 authors], Kovacs P, [80 authors], Tönjes A, [35 authors], Stumvoll M, [87 authors], Loos RJ. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42:937-48.

Taubert M, Draganski B, Anwander A, Müller K, Horstmann A, Villringer A, Ragert P. Dynamic properties of human brain structure: learning-related changes in cortical areas and associated fiber connections. J Neurosci. 2010;30:11670-7.

Ritter P, Moosmann M, Villringer A. Rolandic alpha and beta EEG rhythms' strengths are inversely related to fMRI-BOLD signal in primary somatosensory and motor cortex. Hum Brain Mapp. 2009;30:1168-87.

Führer D, Zysset S, Stumvoll M. Brain activity in hunger and satiety: an exploratory visually stimulated FMRI study. Obesity (Silver Spring). 2008;16:945-50.

Marschner A, Mell T, Wartenburger I, Villringer A, Reischies FM, Heekeren HR. Reward-based decision-making and aging. Brain Res Bull. 2005;67:382-90.

Blankenburg F, Taskin B, Ruben J, Moosmann M, Ritter P, Curio G, Villringer A. Imperceptible stimuli and sensory processing impediment. Science. 2003;299:1864.


Project Leader

Project Leader


Frauke Beyer

Office address: Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig



+49 341 9940-2412


Doctoral Researcher

Ronja Thieleking

Office address: Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103 Leipzig
Phone (lab or office):
+49 341 9940 2407
PhD project description: I am mainly interested in the effects of memory and attention on and the role of the hippocampus and amygdala in making food choices and thereby energy regulation and body weight status. To investigate these effects, we are running a dietary intervention study with functional, structural and diffusion-weighted MR imaging. Body weight status in general and obesity in specific are important factors for cognitive functions and brain structure - therefore, we further evaluate effects of bariatric surgery on these two domains.

Doctoral researcher

Yee Teng Lee (Lilian)


Office address: Max Planck Institute for Human Cognitive and Brain Science, Stephanstraße 1a, 04103 Leipzig
Phone (Lab or office):
+49 341 9940 2431
PhD project description:
I am interested in the association between microbiome, obesity and brain aging. My research focuses on the role of the bidirectional gut-brain axis and its underlying mechanisms that mediate the relationship between obesity and the brain.


Haiko Schlögl

Office address: Department of Endocrinology, Nephrology, Rheumatology
+ 49 341 97 13380


Dr. Daria Jensen

Office address: Max Planck Institute for Human Cognitive and Brain Sciences
Main focus:

My research focuses on the detection of brain connectivity pathways across the lifespan, which are influenced by diet and the microbiome. I am particularly interested in subcortical brain connectivity changes associated with diet and the microbiome, which might be used to explain important pathways related to dementia and/or obesity.

Currently, I am involved in analysing data of the Gut-Brain-Study and the LIFE cohort.