The interaction of fasting, caloric restriction, and diet-induced obesity with 17β-estradiol on the expression of KNDy neuropeptides and their receptors in the female mouse

Mol Cell Endocrinol. 2016 Dec 5;437:35-50. doi: 10.1016/j.mce.2016.08.008. Epub 2016 Aug 6.


Arcuate neurons that coexpress kisspeptin (Kiss1), neurokinin B (Tac2), and dynorphin (Pdyn) mediate negative feedback of 17β-estradiol (E2) on the HPG axis. Previous studies report that fasting and caloric restriction reduce arcuate Kiss1 expression. The objective of this study was to determine the interactions of E2 with fasting, caloric restriction, and diet-induced obesity on KNDy gene and receptor expression. Ovariectomized female mice were separated into control and estradiol benzoate (E2B)-treated groups. E2B decreased Kiss1 and the tachykinin 2 receptor, Tac3r, in ARC tissue and Tac2 in Tac2 neurons. Diet-induced obesity decreased Kiss1 in oil-treated animals and the kisspeptin receptor, Kiss1r and Tac3r in the ARC of E2B-treated animals. Chronic caloric (30%) restriction reduced all three neuropeptides in oil-treated females and Kiss1r by E2B in CR animals. Taken together, our experiments suggest that steroidal environment and energy state negatively regulate KNDy gene expression in both ARC and Tac2 neurons.

Keywords: Arcuate nucleus; Caloric restriction; Diet-induced obesity; Ghrelin; KNDy neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Body Composition
  • Body Weight
  • Caloric Restriction*
  • Diet*
  • Diet, High-Fat
  • Dynorphins / genetics
  • Dynorphins / metabolism
  • Estradiol / blood
  • Estradiol / metabolism*
  • Estradiol / pharmacology
  • Fasting*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Ghrelin / metabolism
  • Kisspeptins / genetics
  • Kisspeptins / metabolism
  • Mice, Inbred C57BL
  • Models, Biological
  • Neurokinin B / genetics
  • Neurokinin B / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Obesity / blood
  • Obesity / genetics
  • Obesity / metabolism*
  • Organ Size
  • Signal Transduction / drug effects
  • Signal Transduction / genetics


  • Ghrelin
  • Kisspeptins
  • Neuropeptides
  • Estradiol
  • Dynorphins
  • Neurokinin B