Impact of early overfeeding on the transcriptional regulation of genes associated with food intake control

LAZZARINO GP; SCHUMACHER R; ANDREOLI MF; ROSSETTI MF; RAMOS JG

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

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Nutritional environment is critical during perinatal period and could impact inhealth in adult life. Litter size reduction is a good experimental model for the studyof early overfeeding and obesity. Our aim was to analyze the effects of earlyoverfeeding on the brain control of food intake in rats at postnatal day (PND) 21.Male offspring were divided in 2 experimental groups: small litter (SL, n=4) ornormal litter (NL, n=10), from PND3 to PND21. On PND21, animals weresacrificed and the body weight and epididymal fat pad (EFP) were measured.Micropunch technique was used to isolate specific nuclei from rat brains. Energyintake control neuropeptides and mesolimbic dopaminergic related genes weremeasured by RT-PCR and their epigenetic control were analyzed (N=10/group).Our results showed than the SL group had higher body and EFP weights thanthe NL group. Moreover, SL rats showed changes in the expression of: a)anorexigenic andorexigenic neuropeptides on specific nuclei ofthehypothalamus; and b) mesolimbic dopaminergic related genes in ventraltegmental area and nucleus accumbens. Changes in gene expression wererelated with the methylation status of their promoter regions, suggesting that theSL group developed an anorectic signal in different regions of the brain controlledby methylation-related mechanisms. Overfeeding during lactation triggered anepigenetic control of genes related with food intake, regulating the body energybalance in SL animals at weaning.