Cafeteria diet induces progressive and differential changes in brain mechanisms involved in food intake control over time

LAZZARINO GP; ANDREOLI MF; ACUTAIN F; SCHUMACHER R; STOKER C; RAMOS JG

Congreso; Reunión Conjunta de Biociencias I; 2017

We aim to determine the effects of Cafeteria diet (CAF),rich in palatable andenergy dense foods, on the expression of key genes of the brain reward system(RW) in the short and long term.FemaleWistar rats were fed chow orCAF for4or11weeks. Animals were sacrificed and 2 regions of the Accumbens Nucleus(NA ? Core, NAC; and shell, NAS), Ventral Pallidum (VP) and VentralTegmental Area (VTA) were dissected.Serum leptin was assessed byRIA.mRNA expression of genes of the dopaminergic and GABAergic pathway,and the leptin receptor (ObRb) was evaluated by qPCR in the nuclei.Data wasstatisticallyanalyzed by two-way ANOVA followed by Tukeypost-test.Fourweeks of CAFincreased energy intake andadiposity,not affecting circulatingleptin or body weight. In VTA, 4 weeks of CAF increased the expression of thedopamine active transporter (DAT)anddecreasedboth isoforms of the enzymeinvolved in the synthesis of GABA(glutamate decarboxylase, GAD 1 and 2),without altering tyrosine hydroxylase (TH) expression. CAF decreaseddopaminereceptor (DR) 2 expression in NAS and increased DR1 levels in NAC. Also,CAF increased GAD2 levels in VP. After 11 weeks of CAF, animals sustainedthe hyperenergetic intake andfurther increased adiposity, leadingtohyperleptinemia andhigher body weight, only concomitantto an increasedexpression of ObRb in VTA.Ourresultsindicate that the higherenergy intake ofCAF animals in the short-term would respond to hedonic mechanisms, given bymolecular deregulations in the RW. The palatability of the diet could lead to ahypodopaminergic state, as DAT expression increase in VTA and DR2decrease in NAS. Besides, the increment in GAD2 expression in VPindicatesaninhibitory GABAergic input to dopaminergic and GABAergic VTA neurons thatmay, inhibit dopamine and GABArelease,in line with the low expressionlevels ofGAD1 and GAD2.Conversely, in the long-term the hypercaloric intake couldrespond to an altered homeostatic control.