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Reward and obesity the role of Neuropeptide Y and leptin Susanne E la Fleur Dept Endocrinology and Metabolism Academic Medical Center University of Amsterdam [email protected] 27th ECNP Congress, Berlin Friedman, Nature 2009 hypothalamus NPY ↓ overeating brain response inhibit eating but obese individuals have high leptin levels but are leptin resistant Friedman, Nature 2009 motivation to eat and the food must be liked Hypothalamus Striatum Hypothalamus Striatum Morton et al, Nature 2006 diet-induced obesity animal model forced diets free-choice diets fcHFHS fcHF fcHS chow fat and sugar induces hyperphagia fcHF fcHFHS b b b a la Fleur et al, Int J Obes 2010 & 2011 a a a a b b a a choice is important for hyperphagia 35% 50% 15% la Fleur et al, Int J Obes 2014 big meals snacking choice with liquid sugar induces SNACKING la Fleur et al, Int J Obes 2014 choice with liquid sugar induces SNACKING la Fleur et al, Int J Obes 2014 rats on fcHFHS are more motivated work for sugar reward * ad lib fat intake la Fleur et al, Int J Obes 2010 & 2011 overeating brain response inhibit eating brain response to overeating adjusting intake overeating brain response to overeating adjusting intake la Fleur et al, Int J Obes 2010 overeating rats on fcHFHS are leptin resistant vd Heuvel et al, JNE, 2014 vd Heuvel et al, Plos one, 2014 brain response to overeating la Fleur et al, Int J Obes 2010 Rats on fcHFHS are more sensitive to NPY CHOW FAT vd Heuvel et al, JNE, 2014 NPY effects on motivation for sugar Pandit et al, Obesity, 2014 NPY in nucleus accumbens increases fat intake vd Heuvel et al, Biol Psych,2014 NPY Y1 receptors on enkephalin neurons in NAc Van den Heuvel et al Biol Psych, 2014 fcHFHS diet lowers Enkephalin mRNA PPE mRNA (AUperc) 150 * 100 50 0 chow Adapted from: Morton et al, Nature 2006 fcHFHS ENK ? Van den Heuvel, Gumbs et al Biol Psychiatry, 2014 NPY neurons in ARC project to NAc Van den Heuvel, Gumbs et al Biol Pscyh, 2014 An fcHFHS diet increases NPY in the ARC decreases ENKmRNA in NAc NPY projections exit between ARC and NAc NPY in the NAc decreases ENKmRNA and neuronal firing NPY in the NAc increases fat intake NPY system is out of balans on fcHFHS NPY rec leptin rec NPY rec NPY leptin rec more motivated for sugar more ad lib fat intake Our PhD students Evita Belegri Aurea Blancas (Strasbourg) Charlene Diepenbroek Myrtille Gumbs Murat Kilicarslan Nicolette Lammers Joëlle Oosterman Rahul Pandit (RMI,Utrecht) Merel Rijnsburger Ruth Versteeg Former PhD students Gitte Tiesjema Esther van der Zwaal Elsmarieke van der Giessen Elodie Girault Jose van den Heuvel Karin Koopman Mireille Serlie Department/AMC Dries Kalsbeek Mariëtte Ackermans Peter Bisschop Anita Boelen Eric Fliers Erik Endert Max Nieuwdorp Jan Booij (Nucl Med) Aart Nederveen (Radiology) Els Nieveen van Dijkum (Surgery) (inter)national Roger Adan (Utrecht, NL) Wiep Scheper (A’dam, NL) Anneke Alkemade (A’dam, NL) Serge Luquet (Paris, FR) Jorge Mendoza (Strasbourg, FR) Ralph diLeone (Yale, USA) Barbara Kahn (Harvard, USA) Mark Herman (Harvard, USA) Denise Belsham (Toronto, CA) Margriet Ouwens (Dusseldorf, DE) Chun-Xia Yi (Munchen, DE) COLLABORATIONS OUR RESEARCH GROUP Technicians Leslie Eggels Unga Unmehopa
