The effects of diet-induced obesity on glucose metabolism in the mouse endometrium
- 1Animal Science Laboratory, Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801 USA
- 2Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801 USA
Abstract
Background: Embryo transfer studies in women with high BMI show lower implantation rates, indicating impaired uterine function. Most mouse studies using diet-induced obesity (DIO) do not characterize the metabolomic phenotype in their models. Additionally, studies usually focus on implantation sites, ignoring the role of the epithelium in supporting embryo development. At proestrus, the uterine epithelium metabolizes glucose for its own needs and stores glycogen to support embryo development after mating. Our objectives were to (1) thoroughly characterize systemic metabolism in a long-term DIO mouse model, and (2) determine how DIO affects glucose metabolism in the uterine epithelium at proestrus.
Methods and results: Mice were randomly assigned to one of three experimental diets (10%, 45%, or 60% kcal from fat) and fed ad libitum. Both high-fat diet (HFD) groups progressively increased in body mass and glucose intolerance during the course of the experiment. After 18 weeks, the mice were sacrificed at proestrus. In serum, gas chromatography-mass spectrometry (GC–MS) showed that HFDs altered the levels of 23 metabolites (P<0.05). Analysis of these metabolites showed enrichment in pathways related to lipids, glucose, and energy metabolism. Confirming that the HFD mice were insulin-resistant, liver glycogen stores decreased, while hepatic triglyceride levels were increased in the 60% fat group, in agreement with observations in obese people. In contrast, effects on the uterus were minimal. There was no difference in immunostaining in the uterus for the glycolytic enzymes PKM2 and PFKM. There was no difference in the glycogen levels or immunostaining for glycogen-metabolizing enzymes in the endometrium. Additionally, immunostaining for phospho-IRS and phospho-AKT in the uterine epithelium was similar across groups, indicating no change in AKT signaling in fasted mice. GC–MS analysis of the uterus found alterations in only 10 metabolites in the 60% fat group relative to the 10% fat group (P<0.05). Analysis of those metabolites found 4 pathways to be significantly enriched—glycosaminoglycan biosynthesis, mannose type O-glycan biosynthesis, linoleic acid metabolism, and purine metabolism.
Conclusion: Our DIO model resulted in systemic traits indicative of insulin resistance. However, obesity had a minimal effect on glucose metabolism in the endometrium at proestrus.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s44494-026-00008-8.
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BibTeX
@article{bhaye2026effects,
title = {{The effects of diet-induced obesity on glucose metabolism in the mouse endometrium}},
author = {Sameeksha Bhaye and Kassandra Sandoval and Chanaka Rabel and Malia D. Berg and Bruce R. Southey and Kelly S. Swanson and Romana A. Nowak and Matthew Dean},
journal = {Uterine Research},
year = {2026},
month = nov,
doi = {10.1186/s44494-026-00008-8},
url = {https://doi.org/10.1186/s44494-026-00008-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The effects of diet-induced obesity on glucose metabolism in the mouse endometrium
AU - Sameeksha Bhaye
AU - Kassandra Sandoval
AU - Chanaka Rabel
AU - Malia D. Berg
AU - Bruce R. Southey
AU - Kelly S. Swanson
AU - Romana A. Nowak
AU - Matthew Dean
PY - 2026
DA - 2026/11/04
JO - Uterine Research
DO - 10.1186/s44494-026-00008-8
UR - https://doi.org/10.1186/s44494-026-00008-8
AB - Background: Embryo transfer studies in women with high BMI show lower implantation rates, indicating impaired uterine function. Most mouse studies using diet-induced obesity (DIO) do not characterize the metabolomic phenotype in their models. Additionally, studies usually focus on implantation sites, ignoring the role of the epithelium in supporting embryo development. At proestrus, the uterine epithelium metabolizes glucose for its own needs and stores glycogen to support embryo development after mating. Our objectives were to (1) thoroughly characterize systemic metabolism in a long-term DIO mouse model, and (2) determine how DIO affects glucose metabolism in the uterine epithelium at proestrus. Methods and results: Mice were randomly assigned to one of three experimental diets (10%, 45%, or 60% kcal from fat) and fed ad libitum. Both high-fat diet (HFD) groups progressively increased in body mass and glucose intolerance during the course of the experiment. After 18 weeks, the mice were sacrificed at proestrus. In serum, gas chromatography-mass spectrometry (GC–MS) showed that HFDs altered the levels of 23 metabolites (P<0.05). Analysis of these metabolites showed enrichment in pathways related to lipids, glucose, and energy metabolism. Confirming that the HFD mice were insulin-resistant, liver glycogen stores decreased, while hepatic triglyceride levels were increased in the 60% fat group, in agreement with observations in obese people. In contrast, effects on the uterus were minimal. There was no difference in immunostaining in the uterus for the glycolytic enzymes PKM2 and PFKM. There was no difference in the glycogen levels or immunostaining for glycogen-metabolizing enzymes in the endometrium. Additionally, immunostaining for phospho-IRS and phospho-AKT in the uterine epithelium was similar across groups, indicating no change in AKT signaling in fasted mice. GC–MS analysis of the uterus found alterations in only 10 metabolites in the 60% fat group relative to the 10% fat group (P<0.05). Analysis of those metabolites found 4 pathways to be significantly enriched—glycosaminoglycan biosynthesis, mannose type O-glycan biosynthesis, linoleic acid metabolism, and purine metabolism. Conclusion: Our DIO model resulted in systemic traits indicative of insulin resistance. However, obesity had a minimal effect on glucose metabolism in the endometrium at proestrus. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s44494-026-00008-8.
SN - 3091-3276
ER -