Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain.

Effect of a low-starch/low-dairy diet on fat oxidation in overweight and obese women with polycystic ovary syndrome

“…Previous research has shown that hyperinsulinemia decreases lipolysis in skeletal muscle, but increases lipolysis in adipose tissue, leading to high levels of circulating fatty acids that further impair insulin signaling and lipid oxidation in skeletal muscle (elevated RER)(Guilherme 2008; Whigham et al 2013). At baseline, the fasting RER for the participants in our study was quite high (0.85±0.05 CO 2 /O 2 ), which provides evidence of impaired fasting fat oxidation in our overweight and obese women with PCOS.…”

“…The I ns1 deficient mice were protected from diet-induced adult-onset weight gain, suggesting that pancreatic insulin hyper-secretion is required for diet-induced obesity and suppressed weight loss. A postprandial rise in insulin increases carbohydrate (CHO) oxidation acutely through the activation of glycolytic enzymes (i.e., phosphofructokinase); these glycolytic enzymes strongly decrease fatty acid oxidation by inhibiting fatty acid transport into mitochondria (Whigham et al 2013). Lipoprotein lipase (LPL) is an enzyme responsible for lipolysis and is regulated by substrate availability; LPL activity is high after a high fat mealand low in the post-absorptive state.…”

Cardiometabolic Risks in Polycystic Ovary Syndrome: Non-Traditional Risk Factors and the Impact of Obesity

“…A normal caloric intake might act as a relatively excessive supply sufficient to exhaust such low capacity [49] , leading to metabolic complications including IR and androgen excess and thus PCOS [49] . Additionally, women with PCOS appear to have diminished use of lipid as an energy substrate, with inflexibility in fasting-related switching between lipid and carbohydrate/protein utilisation for carbon metabolism [50] . Such fat-sparing metabolism may contribute to further weight gain in PCOS [50] .…”

“…Additionally, women with PCOS appear to have diminished use of lipid as an energy substrate, with inflexibility in fasting-related switching between lipid and carbohydrate/protein utilisation for carbon metabolism [50] . Such fat-sparing metabolism may contribute to further weight gain in PCOS [50] .…”

Nutrimetabolomics

“…Dr. Assadi-Porter hypothesized that higher androgen concentrations, inflammation, and insulin resistance (IR) all could contribute to PCOS, which results in this complex phenotype, and used untargeted metabolomics to test this hypothesis. In her recently published work, she used lean and obese non-PCOS subjects and lean and obese PCOS subjects (3). The NMR analyses of fasting serum data showed that the metabolite profiles were different between the 4 groups.…”