|Whigham Grendell, Leah|
|BUTZ, DANIEL - University Of Wisconsin|
|DASHTI, HESAM - University Of Wisconsin|
|TONELLI, MARCO - University Of Wisconsin|
|JOHNSON, LUANN - University Of North Dakota|
|COOK, MARK - University Of Wisconsin|
|PORTER, WARREN - University Of Wisconsin|
|EGHBALNIA, HAMID - University Of Cincinnati|
|MARKLEY, JOHN - University Of Wisconsin|
|LINDHEIM, STEVE - University Of Wisconsin|
|SCHOELLER, DALE - University Of Wisconsin|
|ABBOTT, DAVID - University Of Wisconsin|
|ASSADI-PORTER, FARIBA - University Of Wisconsin|
Submitted to: Current Metabolomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/20/2013
Publication Date: 12/31/2013
Citation: Whigham Grendell, L.D., Butz, D.E., Dashti, H., Tonelli, M., Johnson, L.K., Cook, M.E., Porter, W.P., Eghbalnia, H., Markley, J.L., Lindheim, S.R., Schoeller, D., Abbott, D.H., Assadi-Porter, F.M. 2013. Metabolic evidence of diminished lipid oxidation in women with polycystic ovary syndrome. Current Metabolomics. 1(4): 269-278.
Interpretive Summary: Diseases of unknown causes that may be due to multiple and interacting pathways are referred to as complex diseases. Polycystic ovary syndrome (PCOS) is a complex disease. PCOS remains largely a diagnosis of exclusion despite being the most common female endocrine disorder and the leading cause of metabolic syndrome, obesity, and type 2 diabetes mellitus (T2DM) in young women. New tools for early diagnosis are urgently needed to reduce co-morbidities of PCOS. We used exhaled breath stable carbon isotopes analysis coupled with analyses of metabolic pathways associated with classic PCOS phenotypes. Breath analysis shows PCOS women have reduced diurnal variation in transitioning between carbohydrate and lipid metabolism. Analysis of overnight fasted serum by nuclear magnetic resonance (NMR) indicates increased glucogenic amino acids in serum. Thus, the metabolic inflexibility observed in PCOS women may underlie metabolic dysregulation in which lipid oxidation is decreased at the expense of substituting protein to support fasting energy requirements.
Technical Abstract: Complex diseases, such as polycystic ovary syndrome (PCOS), are not limited to specific genes, pathogens, toxicoses, or identifiable environmental influences. PCOS still remains a diagnosis of exclusion despite being the most common female endocrinopathy and the leading cause of metabolic syndrome, obesity and type 2 diabetes mellitus (T2DM) in young women. To identify early markers and clarify diagnosis to reduce co-morbidities associated with PCOS, we used exhaled breath stable carbon isotope analysis coupled with an untargeted metabolomic approach to study underlying metabolic pathways associated with non-obese, severe PCOS phenotype (n=7) compared to non-obese controls (n=6). Breath analysis shows PCOS women have reduced daily variation (i.e. change from morning to midday delta value of 3.2‰ for normal and 1.0‰ for PCOS; p<0.03) in transitioning between lipid and carbohydrate/protein metabolism. Analysis of overnight fasted serum by nuclear magnetic resonance (NMR) indicates increased concentration of glucogenic amino acids. Metabolic inflexibility observed in non-obese women with severe PCOS, in which lipid oxidation is decreased at the expense of substituting protein to support fasting energy requirements, may contribute to pathogenic mechanisms underlying PCOS metabolic dysregulation.