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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #350497

Title: Obesity leads to distinct metabolomic signatures in the follicular fluid of women undergoing in vitro fertilization

Author
item RUEBEL, MEGHAN - Michigan State University
item PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC)
item MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC)
item PACK, LINDSAY - Arkansas Children'S Nutrition Research Center (ACNC)
item MOUTOS, DEAN - Arkansas Fertility & Gynecology
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)
item ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/31/2018
Publication Date: 1/2/2019
Citation: Ruebel, M.L., Piccolo, B.D., Mercer, K.E., Pack, L., Moutos, D., Shankar, K., Andres, A. 2019. Obesity leads to distinct metabolomic signatures in the follicular fluid of women undergoing in vitro fertilization. American Journal of Physiology - Endocrinology and Metabolism. https://doi.org/10.1152/ajpendo.00401.2018.
DOI: https://doi.org/10.1152/ajpendo.00401.2018

Interpretive Summary: The follicular fluid that surrounds the human egg provides a rich source of nutrients and growth factors requisite for egg growth, development and viability. The objective of this study was to understand the impact of obesity on the follicular fluid milieu in normal weight and overweight/obese women undergoing fertility treatments. Several follicular fluid metabolites were elevated in overweight/obese compared to normal weight women, including: uric acid, isothreonic acid, 2-deoxytetronic acid, alpha-ketoglutarate, glycerol, shikimic acid, and 9 unknown metabolites. Several follicular fluid metabolites were lower in overweight/obese compared to normal weight women, including: 2-dimethylacetal ketoglucose, aminomalonate, salicylic acid, lysophosphatidylcholine, glucosyl ceramide and 8 unknown metabolites. The metabolite indole-3-propionic acid was decreased in both follicular fluid and serum of overweight/obese compared to normal weight women. In this study, we identified obesity-associated changes in follicular fluid metabolites related to oxidative stress, antioxidant capacity, fatty acid oxidation, and lipid metabolism. The highly significant correlation between indole-3-propionic acid in serum and follicular fluid, suggests a potential serum biomarker of indole-3-propionic acid levels in follicular fluid. Taken together, these results suggest that obesity has important consequences on the follicular environment during the pre-conception period, a window of time that may be important for lifestyle interventions to ameliorate obesity-associated risk factors.

Technical Abstract: While obesity negatively influences the metabolic homeostasis of cells within a broad range of tissues, its impact on oocyte metabolism is not fully understood. Prior evidence suggests obesity increases expression of oocyte genes associated with inflammation, oxidative stress, and lipid metabolism; however, the metabolic impact of these genetic differences is not known. To address this gap, we conducted an exploratory assessment of the follicular fluid (FF) metabolome in 8 overweight/obese (OW) and 9 normal weight (NW) women undergoing in vitro fertilization. FF and serum were collected and analyzed by untargeted metabolomics using GC-QTOF-MS and CSH-ESI QTOF MS/MS. Untargeted metabolomics identified obesity-associated changes in FF metabolites related to oxidative stress/antioxidant capacity, xenometabolism/amino acid biosynthesis, and lipid metabolism. Discriminant FF metabolites included elevated uric acid, isothreonic acid, 1 unknown primary metabolite, and 6 unknown complex lipids in OW compared to NW women. Conversely, 2-dimethylacetal-ketoglucose, aminomalonate, 2 unknown primary metabolites, and 2 unknown complex lipids were decreased in FF of OW relative to NW women. Indole-3-propionic acid (IPA), a bacterial derived metabolite, was also decreased in both FF and serum of OW women (p<0.05). The significant correlation between antioxidant IPA in serum and FF (R= 0.95, p<0.0001), suggests a potential serum biomarker of FF antioxidant status or reflection of the gut metabolism interaction with the follicle. These results suggest that obesity has important consequences on the follicular environment during the pre-conception period, a window of time that may be important for lifestyle interventions to ameliorate obesity-associated risk factors.