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

Mol Cell Endocrinol. 2017 Jul 15:450:113-125. doi: 10.1016/j.mce.2017.05.005. Epub 2017 May 4.

Abstract

We evaluated the effect of cafeteria diet (CAF) on the mRNA levels and DNA methylation state of feeding-related neuropeptides, and neurosteroidogenic enzymes in discrete hypothalamic nuclei. Besides, the expression of steroid hormone receptors was analyzed. Female rats fed with CAF from weaning increased their energy intake, body weight, and fat depots, but did not develop metabolic syndrome. The increase in energy intake was related to an orexigenic signal of paraventricular (PVN) and ventromedial (VMN) nuclei, given principally by upregulation of AgRP and NPY. This was mildly counteracted by the arcuate nucleus, with decreased AgRP expression and increased POMC and kisspeptin expression. CAF altered the transcription of neurosteroidogenic enzymes in PVN and VMN, and epigenetic mechanisms associated with differential promoter methylation were involved. The changes observed in the hypothalamic nuclei studied could add information about their differential role in food intake control and how their action is disrupted in obesity.

Keywords: Cafeteria diet; DNA methylation; Hormone receptors; Neuropeptides; Neurosteroidogenic enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Binding Sites
  • Body Weight
  • Computer Simulation
  • DNA Methylation / genetics*
  • Diet*
  • Eating / genetics*
  • Energy Intake / genetics
  • Female
  • Gene Expression Regulation*
  • Glucose Tolerance Test
  • Hypothalamus / metabolism*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Organ Size / genetics
  • Paraventricular Hypothalamic Nucleus / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Steroids / metabolism
  • Transcription, Genetic
  • Ventromedial Hypothalamic Nucleus / metabolism

Substances

  • Neuropeptides
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Steroids