title: Sex- and age-dependent effects of Gpr30 genetic deletion on the metabolic and cardiovascular profiles of diet-induced obese mice.
abstract: The G protein-coupled receptor 30 (GPR30) has been claimed as an estrogen receptor. However, the literature reports controversial findings and the physiological function of GPR30 is not fully understood yet. Consistent with studies assigning a role of GPR30 in the cardiovascular and metabolic systems, GPR30 expression has been reported in small arterial vessels, pancreas and chief gastric cells of the stomach. Therefore, we hypothesized a role of GPR30 in the onset and progression of cardiovascular and metabolic diseases. In order to test our hypothesis, we investigated the effects of a high-fat diet on the metabolic and cardiovascular profiles of Gpr30-deficient mice (GPR30-lacZ mice). We found that GPR30-lacZ female, rather than male, mice had significant lower levels of HDL along with an increase in fat liver accumulation as compared to control mice. However, two indicators of cardiac performance assessed by echocardiography, ejection fraction and fractional shortening were both decreased in an age-dependent manner only in Gpr30-lacZ male mice. Collectively our results point to a potential role of Gpr30 in preserving lipid metabolism and cardiac function in a sex- and age-dependent fashion.
authors.affiliation: Center for Cardiovascular Research-Charité, Hessische Str. 3-4, 10115 Berlin, Germany. Electronic address: luca.meoli@childrens.harvard.edu.
authors.forename: Luca
authors.initials: L
authors.lastname: Meoli
authors.affiliation: Center for Cardiovascular Research-Charité, Hessische Str. 3-4, 10115 Berlin, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Isensee
authors.affiliation: Center for Cardiovascular Research-Charité, Hessische Str. 3-4, 10115 Berlin, Germany.
authors.forename: Valeria
authors.initials: V
authors.lastname: Zazzu
authors.affiliation: Center for Cardiovascular Research-Charité, Hessische Str. 3-4, 10115 Berlin, Germany.
authors.forename: Christoph S
authors.initials: CS
authors.lastname: Nabzdyk
authors.affiliation: Center for Cardiovascular Research-Charité, Hessische Str. 3-4, 10115 Berlin, Germany.
authors.forename: Dian
authors.initials: D
authors.lastname: Soewarto
authors.affiliation: Center for Cardiovascular Research-Charité, Hessische Str. 3-4, 10115 Berlin, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Witt
authors.affiliation: Center for Cardiovascular Research-Charité, Hessische Str. 3-4, 10115 Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Foryst-Ludwig
authors.affiliation: Center for Cardiovascular Research-Charité, Hessische Str. 3-4, 10115 Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kintscher
authors.affiliation: Center for Cardiovascular Research-Charité, Hessische Str. 3-4, 10115 Berlin, Germany.
authors.forename: Patricia Ruiz
authors.initials: PR
authors.lastname: Noppinger
mesh_terms: D050154:Adiposity; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001783:Blood Flow Velocity; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D006321:Heart / Q000503:physiopathology*; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics*; D012727:Sex Characteristics; D013318:Stroke Volume
chemical_list: C532507:GPER1 protein, mouse; D008075:Lipoproteins, HDL; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Cardiac phenotype; DIO mice; GPR30; GPR30 KO mice; HDL