Abstract
Ovarian malfunction caused by a high-fat diet is reversed with short-term treatment with the anti-diabetic drug rosiglitazone
Cadence Ellen Minge
PhD student, University of Adelaide, Discipline of Obstetrics & Gynaecology
Supervised through Obstetrics and Gynaecology, University of Adelaide
One of the most alarming health crises affecting people in developed countries, including Australia is the escalating prevalence of obesity and the wide-ranging complications associated with this epidemic. By placing people at an increased risk of coronary heart disease, stroke, colorectal cancer and kidney disease,
- obesity already accounts for at least 30% of the total disease burden in Australia.
- new research from our laboratory adds to concerns for Australia's future health status.
We report that female mice consuming a high-fat "Western" style diet develop severe reproductive abnormalities that mirror emerging reports of human obesity-related infertility. Using this model we have identified specific stages of egg maturation and early embryonic development most affected by high fat diet, and also metabolic disturbances that are likely involved. We have discovered that sensitivity to glucose and insulin are the most important measurements to indicate reproductive health. We have now also produced valuable information identifying the molecular signalling pathways operating inside ovarian cells that are at fault, and we have conducted trials of existing pharmacological therapies that could reverse these effects. We report that short-term, pre-ovulatory treatment with the widely prescribed anti-diabetic drug rosiglitazone (Avandia, GlaxoSmithKline) is incredibly successful at completely reversing many aspects of infertility associated with obesity. This is due to specific targeting of ovarian tissue by rosiglitazone, compared to other agents not as active within the ovary.
