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GPER Deficiency in Male Mice Results in Insulin Resistance, Dyslipidemia, and a Proinflammatory State
Open accessAbstract
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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“GPER1 KO mice are more prone to obesity, insulin resistance, inflammation, and dyslipidemia than control mice (147–149).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [148]
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Metadata
- 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.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2013-11-01
- Volume
- 154
- Issue
- 11
- Pages
- 4136-4145
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- 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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