Cafeteria diet temporarily affects brain reward dopaminergic pathway through NNA methylation mechanisms.

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

Congreso; Congreso Sociedad Argentina de Neurociencias (SAN); 2018

We analysed the short and long-term effects of a highly palatable cafeteria diet(CAF)intake on the expression of key genes of the reward dopaminergic pathway of thebrain(RW). Female rats were fed chow or CAF for 4(CAF4) or 11(CAF11) weeks.Ventral Tegmental Area(VTA), Accumbens Nucleus Core(NAC) and Shell(NAS), andVentral Pallidum(VP) were isolated by micropunching technique. For mRNA analysis,qPCR was performed. Digestion with methylation-sensitive restriction enzymesfollowed by qPCR was used for epigenetic studies. Serum leptin was assessed by RIA.CAF4 increased energy intake and adiposity. In VTA, CAF4 enhanced dopamine activetransporter(DAT) and decreased both isoforms of glutamate decarboxylase(GAD),without altering Tyrosine Hydroxylase levels. CAF4 decreased dopamine receptor 2mRNA in NAS and increased GAD2 levels in VP. The changes in DAT mRNA wererelated to a decrease in the methylation status of its promoter region. CAF11 furtherincreased energy intake and adiposity, leading to hyperleptinemia, and increased mRNAof leptin receptor in VTA, without affecting the expression of any gene of the RWstudied. Our results indicate that, in the short-term, CAF deregulates the RW, at least inpart via epigenetic changes, possibly reflecting a state of RW hyposensitivity, whichmight promote the excessive intake of palatable foods to compensate this status. This isreverted in the long-term, when the hypercaloric intake could respond to an alteredhomeostatic control.