The link between fat and fertility

Drs Greg Anderson and Janette Quennell at the University's Centre for Neuroendocrinology are investigating how fertility-regulating neurons in the brain respond to nutritional signals secreted by fat cells or the gut.

It comes as no surprise to clinicians, ecologists and livestock farmers that body condition and fertility are closely linked.

For example, women with very high or low amounts of body fat frequently have irregular menstrual cycles and difficulty becoming pregnant.

It is unclear how the reproductive centres in the brain pick up these metabolic signals.

Fat releases a hormone called leptin that tells the brain how much body fat is stored.

A defective leptin molecule leads to obesity and infertility, but a prolonged high fat diet can create the same effect by causing brain cells to become unresponsive to leptin.

Leptin is capable of entering the brain and may be able to act directly on gonadotrophin-releasing hormone (GnRH) neurons (the cells in the brain that drive fertility).

Alternatively, leptin may stimulate other brain cells or tissues outside of the brain, such as the reproductive organs, to promote reproductive competence.

Drs Anderson and Quennell used knockout transgenic technology to assess the fertility of mice in which leptin receptors were deleted from either all brain neurons or from GnRH neurons only.

Transgenic mice with no leptin receptors present in any brain neurons resulted in profound infertility in males and females.

However, mice with GnRH neuron-specific deletion of leptin receptors exhibited normal fertility.

Additionally, highly sensitive techniques were used to screen individual GnRH neurons for the presence of leptin receptors.

No GnRH neurons showed any sign of leptin receptors.

Collectively, these results show that leptin does not act directly on GnRH neurons, but leptin does regulate fertility by acting in the brain rather than peripheral tissues.

The location and identity of these leptin-responsive neurons remains to be elucidated.

Exciting new data point to a protein called kisspeptin as a likely candidate.

This work has recently been published in a leading biomedical research journal: Endocrinology.

The Health Research Council of New Zealand is currently funding this important research.