Cafeteria diet differentially alters the expression of feeding-related genes through DNA methylation mechanisms in individual hypothalamic nuclei

LAZZARINO, GISELA PAOLA; ANDREOLI, MARÍA FLORENCIA; ROSSETTI, MARÍA FLORENCIA; STOKER, CORA; TSCHOPP, MARÍA VIRGINA; LUQUE, ENRIQUE HUGO; RAMOS, JORGE GUILLERMO

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Año: 2017

0303-7207

We evaluated the effect of cafeteria diet (CAF) on the mRNAlevels and DNA methylation state of feeding-related neuropeptides, andneurosteroidogenic enzymes in discrete hypothalamic nuclei. Besides, theexpression of steroid hormone receptors was analyzed. Female rats fedwith CAF from weaning increased their energy intake, body weight, and fatdepots, but did not develop metabolic syndrome. The increase in energyintake was related to an orexigenic signal of paraventricular (PVN) andventromedial (VMN) nuclei, given principally by upregulation of AgRP andNPY. This was mildly counteracted by the arcuate nucleus, with decreasedAgRP expression and increased POMC and kisspeptin expression. CAF alteredthe transcription of neurosteroidogenic enzymes in PVN and VMN, andepigenetic mechanisms associated with differential promoter methylationwere involved. The changes observed in the hypothalamic nuclei studiedcould add information about their differential role in food intakecontrol and how their action is disrupted in obesity.