Neonatal overfeeding alters the functioning of the mesolimbic dopaminergic circuitry involving changes in DNA methylation and effects on feeding behavior.

SCHUMACHER R; ROSSETTI MF; CANESINI G; GAYDOU L; GARCÌA, AP; LAZZARINO GP; FERNANDEZ PR; STOKER C; CARRIO MJ; ANDREOLI MF; RAMOS JG

JOURNAL OF NUTRITIONAL BIOCHEMISTRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2023

0955-2863

Mesolimbic dopaminergic circuit is essential for food reward and motivationalbehaviors, and can contribute to weight gain and obesity. Litter reduction is a classical modelfor studying the effects of neonatal overfeeding and overweight. Litters of Wistar rats werereduced to 4 pups/dam for Small Litter (SL) and 10 pups/dam for normal litter at postnatalday (PND) 4. Immediately after performing the feeding behavior tests, the animals weresacrificed in PND21 and PND90. The ventral tegmental area (VTA), Nucleus AccumbensCore (NAcC) and Shell (NAcSh) were isolated from frozen brain sections using the Palkovitsmicro-punch technique. RNA and DNA were extracted from these areas, gene expressionwas measured by RT-qPCR and DNA methylation levels were measured by MSRM-qPCRtechnique. SL-PND21 animals presented increased expression levels of TyrosineHydroxylase and Dopamine Receptor D2 in VTA, decreased expression levels of DopamineActive Transporter (DAT) in VTA, and higher expression levels of DAT in NAcC. On theother hand, SL-PND90 animals showed decreased expression levels of Dopamine ReceptorD1 and higher expression of DAT in NAcSh. These animals also evidenced impairedsensory-specific satiety. In addition, altered promoter methylation was observed at weaning, and remained in adulthood. This work demonstrates that neonatal overfeeding inducesdisruptions in the mesolimbic dopaminergic circuitry and cause alterations in feedingbehavior from weaning to adulthood, suggesting that the neonatal period is critical for thenormal development of dopaminergic circuit that impact on feeding behavior.