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)
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