Cafeteria diet temporarily affects brain reward dopaminergic pathway through DNA methylation mechanisms

ANDREOLI, M. FLORENCIA; SCHUMACHER, ROCÍO; ACUTAIN, M. FLORENCIA; STOKER, CORA; LAZZARINO, GISELA P; ROSSETTI, MARÍA FLORENCIA; RAMOS, JORGE G

Cordoba

Congreso; XXXIII Congreso Anual Sociedad Argentina de Investigación en Neurociencias (SAN 2018); 2019

We analyzed the short- and long-term effects of a highlypalatable cafeteria diet (CAF) intake on the expression ofkey genes of the reward dopaminergic pathway of the brain(RW). Female rats were fed chow or CAF for 4(CAF4) or 11(CAF11) weeks. Ventral Tegmental Area (VTA), AccumbensNucleus Core (NAC) and Shell (NAS), and Ventral Pallidum(VP) were isolated by micropunching technique. For mRNAanalysis, qPCR was performed. Digestion with methylationsensitiverestriction enzymes followed by qPCR was usedfor epigenetic studies. Serum leptin was assessed by RIA.CAF4 increased energy intake and adiposity. In VTA, CAF4enhanced dopamine active transporter (DAT) and decreasedboth isoforms of glutamate decarboxylase (GAD), withoutaltering tyrosine hydroxylase levels. CAF4 decreased dopaminereceptor 2 mRNA in NAS and increased GAD2 levelsin VP. The changes in DAT mRNA were related to adecrease in the methylation status of its promoter region.CAF11 further increased energy intake and adiposity, leadingto hyperleptinemia, and increased mRNA of leptin receptorin VTA, without affecting the expression of any gene of theRW studied. Our results indicate that, in the short term,CAF deregulates the RW, at least in part via epigeneticchanges, possibly reflecting a state of RW hyposensitivity,which might promote the excessive intake of palatablefoods to compensate this status. This is reverted in thelong term, when the hypercaloric intake could respond toan altered homeostatic control.