title: GPER deficiency in male mice results in insulin resistance, dyslipidemia, and a proinflammatory state.
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.
authors: Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico 87131. eprossnitz@salud.unm.edu.
authors: Geetanjali
authors: G
authors: Sharma
authors: Chelin
authors: C
authors: Hu
authors: Jonathan L
authors: JL
authors: Brigman
authors: Gang
authors: G
authors: Zhu
authors: Helen J
authors: HJ
authors: Hathaway
authors: Eric R
authors: ER
authors: Prossnitz
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D050171:Dyslipidemias / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D018149:Glucose Intolerance / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D016207:Cytokines; C532507:GPER1 protein, mouse; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled
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