Cited by 215Estrogen and related hormone effectsAdipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and Obesity

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GPER Deficiency in Male Mice Results in Insulin Resistance, Dyslipidemia, and a Proinflammatory State

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Sharma, Geetanjali, Hu, Chelin, Brigman, Jonathan L., Zhu, Gang, Hathaway, Helen J., Prossnitz, Eric R.·2013·Endocrinology

DOI 10.1210/en.2013-1357PMC PMC3800768

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Abstract

Estrogen is an important regulator of metabolic syndrome, a collection of abnormalities including obesity, insulin resistance/glucose intolerance, hypertension, dyslipidemia, and inflammation, which together lead to increased risk of cardiovascular disease and diabetes. The role of the G protein-coupled estrogen receptor (GPER/GPR30), particularly in males, in these pathologies remains unclear. We therefore sought to determine whether loss of GPER contributes to aspects of metabolic syndrome in male mice. Although 6-month-old male and female GPER knockout (KO) mice displayed increased body weight compared with wild-type littermates, only female GPER KO mice exhibited glucose intolerance at this age. Weight gain in male GPER KO mice was associated with increases in both visceral and sc fat. GPER KO mice, however, exhibited no differences in food intake or locomotor activity. One-year-old male GPER KO mice displayed an abnormal lipid profile with higher cholesterol and triglyceride levels. Fasting blood glucose levels remained normal, whereas insulin levels were elevated. Although insulin resistance was evident in GPER KO male mice from 6 months onward, glucose intolerance was pronounced only at 18 months of age. Furthermore, by 2 years of age, a proinflammatory phenotype was evident, with increases in the proinflammatory and immunomodulatory cytokines IL-1β, IL-6, IL-12, TNFα, monocyte chemotactic protein-1, interferon γ-induced protein 10, and monokine induced by interferon gamma and a concomitant decrease in the adipose-specific cytokine adiponectin. In conclusion, our study demonstrates for the first time that in male mice, GPER regulates metabolic parameters associated with obesity and diabetes.

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Additional file 4 of Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs
Qiu, Y., Ding, R., Zhuang, Z., Wu, J., Yang, M., Zhou, S., Ye, Y., Geng, Q., Xu, Z. Q., Huang, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14561379
Additional file 6 of Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs
Qiu, Y., Ding, R., Zhuang, Z., Wu, J., Yang, M., Zhou, S., Ye, Y., Geng, Q., Xu, Z. Q., Huang, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14561385
Additional file 2 of Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs
Qiu, Y., Ding, R., Zhuang, Z., Wu, J., Yang, M., Zhou, S., Ye, Y., Geng, Q., Xu, Z. Q., Huang, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14561373
Additional file 3 of Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs
Qiu, Y., Ding, R., Zhuang, Z., Wu, J., Yang, M., Zhou, S., Ye, Y., Geng, Q., Xu, Z. Q., Huang, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14561376
Additional file 1 of Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs
Qiu, Y., Ding, R., Zhuang, Z., Wu, J., Yang, M., Zhou, S., Ye, Y., Geng, Q., Xu, Z. Q., Huang, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14561370
Additional file 7 of Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs
Qiu, Y., Ding, R., Zhuang, Z., Wu, J., Yang, M., Zhou, S., Ye, Y., Geng, Q., Xu, Z. Q., Huang, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14561388
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Cryo-EM structure of the bicarbonate receptor GPR30Preprint
Kaneda, S., Jo-Watanabe, A., Akasaka, H., Oshima, H. S., Yokomizo, T., Shihoya, W., & Nureki, O. (2024) · eLife · doi:10.7554/elife.99874.1
eLife Assessment: Cryo-EM structure of the bicarbonate receptor GPR30
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Kaneda, S., Jo-Watanabe, A., Akasaka, H., et al. (2024) · eLife · doi:10.7554/elife.99874.1.sa0
Reviewer #1 (Public Review): Cryo-EM structure of the bicarbonate receptor GPR30
Kaneda, S., Jo-Watanabe, A., Akasaka, H., et al. (2024) · eLife · doi:10.7554/elife.99874.1.sa2
Reviewer #2 (Public Review): Cryo-EM structure of the bicarbonate receptor GPR30
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Cryo-EM structure of the bicarbonate receptor GPR30Preprint
Kaneda, S., Jo‐Watanabe, A., Akasaka, H., Oshima, H. S., Yokomizo, T., Shihoya, W., & Nureki, O. (2025) · eLife · doi:10.7554/elife.99874.2
Additional file 5 of Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs
Qiu, Y., Ding, R., Zhuang, Z., Wu, J., Yang, M., Zhou, S., Ye, Y., Geng, Q., Xu, Z., Huang, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14561382
Additional file 11 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703643
Additional file 14 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703652
Additional file 1 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703610
Additional file 9 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703637
Additional file 13 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703649
Additional file 17 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703661
Additional file 2 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703613
Additional file 3 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703616
Additional file 12 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703646
Additional file 16 of Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments
Fernández‐Arjona, M. D. M., Navarro, J. A., López-Gambero, A. J., de Ceglia, M., Rodríguez, M., Rubio, L., de Fonseca, F. R., Barrios, V., Chowen, J. A., Argente, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26703658

Authors: Sharma, G., Hu, C., Brigman, J. L., Zhu, G., Hathaway, H. J., & Prossnitz, E. R.
Affiliations: UNM Comprehensive Cancer Center (US)
University of New Mexico (US)
Bruker (United States) (US)
Corresponding author: Prossnitz, Eric R.
ORCID: Sharma, Geetanjali
Hu, Chelin
Brigman, Jonathan L.
Zhu, Gang
Hathaway, Helen J.
Prossnitz, Eric R.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2013-11-01
Volume: 154
Issue: 11
Pages: 4136-4145
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2013-1357
PMC: PMC3800768
OpenAlex: W2116524480
Cited by: 210
References: 61
Citations by year: 2026: 5 · 2025: 12 · 2024: 35 · 2023: 12 · 2022: 17 · 2021: 23 · 2020: 15 · 2019: 10 · 2018: 13 · 2017: 24 · 2016: 13 · 2015: 11 · 2014: 15 · 2013: 2
FWCI: 9.07
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Endocrinology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (UL1TR000041, UL1TR001449)
U.S. Public Health Service (1ULRR31977)
School of Medicine, University of New Mexico
Clinical and Translational Science Center, University of New Mexico
National Institute on Alcohol Abuse and Alcoholism (K22AA020303)
National Cancer Institute (R01CA127731, R01CA163890)
National Institute of General Medical Sciences (P30 GM10340)
National Center for Advancing Translational Sciences
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: G protein-coupled estrogen receptor, GPR30, metabolic syndrome, insulin resistance, impaired glucose tolerance, dyslipidemia, obesity, inflammation, adipose tissue, cytokines, adiponectin, male mice, estrogen
MeSH terms: Animals, Female, Gene Expression Regulation, Inflammation, Insulin Resistance, Male, Mice, Inbred C57BL, Receptors, Estrogen, Cytokines, Glucose Intolerance, Mice, Knockout, Receptors, G-Protein-Coupled, Dyslipidemias, Mice, Adiponectin

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GPER Deficiency in Male Mice Results in Insulin Resistance, Dyslipidemia, and a Proinflammatory State

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