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

LAZZARINO GP; ANDREOLI MF; ACUTAIN MF; SCHUMACHER ROCÍO; STOKER C; RAMOS J G

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SAIC

We aim to determine the effects of Cafeteria diet (CAF),rich in palatable and energy 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 for4 or11weeks. Animals were sacrificed and 2 regions of the Accumbens Nucleus (NA ? Core, NAC; and shell, NAS), Ventral Pallidum (VP) and Ventral Tegmental Area (VTA) were dissected.Serum leptin was assessed by RIA.mRNA expression of genes of the dopaminergic and GABAergic pathway, and the leptin receptor (ObRb) was evaluated by qPCR in the nuclei.Data was statisticallyanalyzed by two-way ANOVA followed by Tukeypost-test.Four weeks of CAFincreased energy intake andadiposity,not affecting circulating leptin or body weight. In VTA, 4 weeks of CAF increased the expression of the dopamine active transporter (DAT)anddecreasedboth isoforms of the enzyme involved in the synthesis of GABA(glutamate decarboxylase, GAD 1 and 2), without altering tyrosine hydroxylase (TH) expression. CAF decreaseddopamine receptor (DR) 2 expression in NAS and increased DR1 levels in NAC. Also, CAF increased GAD2 levels in VP. After 11 weeks of CAF, animals sustained the hyperenergetic intake andfurther increased adiposity, leading tohyperleptinemia andhigher body weight, only concomitantto an increased expression of ObRb in VTA.Ourresultsindicate that the higherenergy intake of CAF animals in the short-term would respond to hedonic mechanisms, given by molecular deregulations in the RW. The palatability of the diet could lead to a hypodopaminergic state, as DAT expression increase in VTA and DR2 decrease in NAS. Besides, the increment in GAD2 expression in VPindicates aninhibitory GABAergic input to dopaminergic and GABAergic VTA neurons that may, inhibit dopamine and GABArelease,in line with the low expressionlevels of GAD1 and GAD2.Conversely, in the long-term the hypercaloric intake could respond to an altered homeostatic control.Keywords: Cafeteria diet ? obesity ? mesolimbic system ? energy intake