High-fat diet and type 2 diabetes induced disruption of the oestrous cycle and alteration of hormonal profiles, but did not affect subpopulations of KNDy neurones in female rats

J Neuroendocrinol. 2018 Nov;30(11):e12651. doi: 10.1111/jne.12651. Epub 2018 Nov 7.

Abstract

Apart from the primary metabolic symptoms of obesity and/or diabetes, there are numerous secondary problems, including disruptions of the reproductive system. The KNDy neurones, which express kisspeptin, neurokinin B and dynorphin A and are located in the arcuate nucleus of the hypothalamus (ARC), are important regulators of reproduction. Their functions are highly influenced by metabolic and hormonal status. We have previously shown that, in male rats with experimentally-induced diabetes type 2 (but not with high-fat diet-induced obesity), there are alterations in the number of these cells. In the present study, we hypothesised that a high-fat diet (HFD) and/or diabetes type 2 (DM2) in female rats affect the oestrous cycle, hormonal profiles and the number of kisspeptin-immunoreactive, neurokinin B-immunoreactive and/or dynorphin A-immunoreactive neurones in the ARC. Rats were assigned to one of three groups: a control group fed a regular chow diet, a high-fat diet group (HFD) and a diabetic group (DM2), with both of the latter two groups receiving a high calorie diet (50% of energy from lard). The third group was additionally treated with streptozotocin to induce DM2. Their oestrous cycles was monitored and their metabolic and hormonal status were assessed. We found that HFD and DM2 female rats, despite having significant alterations in their metabolic and hormonal profiles, as well as disruptions of the oestrous cycle, showed no changes in the number of the kisspeptin-immunoreactive, neurokinin B-immunoreactive and/or dynorphin A-immunoreactive neurones in the ARC. However, slight differences in the rostrocaudal distribution of these neurones among groups were reported. In conclusion, the data from the present study, together with our previously published results in males, indicate sex differences in the response of KNDy neurones to DM2 but not to HFD conditions.

Keywords: KNDy neurones; diabetes; kisspeptin; obesity; oestrogen.

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diet, High-Fat*
  • Dynorphins / metabolism
  • Estrous Cycle / metabolism*
  • Female
  • Insulin / metabolism
  • Kisspeptins / metabolism
  • Leptin / metabolism
  • Neurokinin B / metabolism
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Peptide Hormones / metabolism*
  • Rats, Wistar

Substances

  • Insulin
  • Kisspeptins
  • Leptin
  • Neuropeptides
  • Peptide Hormones
  • Dynorphins
  • Neurokinin B