Sex- and age-dependent effects of Gpr30 genetic deletion on the metabolic and cardiovascular profiles of diet-induced obese mice

Meoli, Luca; Isensee, Jörg; Zazzu, Valeria; Nabzdyk, Christoph S.; Soewarto, Dian; Witt, Henning; Foryst‐Ludwig, Anna; Kintscher, Ulrich; Noppinger, Patricia Ruiz

doi:10.1016/j.gene.2014.02.036

Cited by 39 publications

(36 citation statements)

References 63 publications

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“…G-1 administered prior to myocardial ischemia reperfusion also protects both male and female Sprague Dawley rats by improving contractile function and reducing infarct size (78). In contrast to these studies showing protective effects of GPER on both sexes, GPER deletion impairs left ventricular cardiac function in males but not females (79). Some cardioprotective effects of GPER may be centrally mediated, as G-1 microinjection into the nucleus ambiguous of male Wistar rats decreases cardiac vagal tone (80).…”

Section: Heart Failurecontrasting

confidence: 74%

“…In contrast, Mårtensson et al reported that genetic deletion of GPER reduces body weight in females with no alterations in males and correlates with decreased skeletal growth rather than alterations in adiposity (31). In Gpr30-lacZ mice fed either a normal or high fat diet, body weight, body mass composition, and glucose tolerance are not altered in males or females (79). However, these female knockout mice have reduced plasma high density lipoproteins and increased fat content in the liver compared to wildtype controls, with no alterations in males.…”

Section: Metabolic Disordersmentioning

confidence: 99%

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GPER–novel membrane oestrogen receptor

et al. 2016

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The recent discovery of the G protein-coupled estrogen receptor (GPER) presents new challenges and opportunities for understanding the physiology, pathophysiology, and pharmacology of many diseases. This review will focus on the expression and function of GPER in hypertension, kidney disease, atherosclerosis, vascular remodeling, heart failure, reproduction, metabolic disorders, cancer, environmental health, and menopause. Furthermore, this review will highlight the potential of GPER as a therapeutic target.

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Section: Heart Failurecontrasting

confidence: 74%

Section: Metabolic Disordersmentioning

confidence: 99%

GPER–novel membrane oestrogen receptor

et al. 2016

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“…high levels of LDL cholesterol and triglycerides, is a major risk factor for the development of coronary atherosclerosis and is typically found in patients with obesity, insulin resistance, or diabetes, translating into an increased cardiovascular risk [1, 2]. Decreased HDL cholesterol and increased triglyceride levels [60] are observed in female GPER 0 mice (GPER- lacZ reporter with a partial deletion of the GPER coding sequence) in association with hepatic steatosis [88, 89]. In female mice under atherogenic conditions, deletion of GPER increases total and LDL cholesterol levels [46].…”

Section: Gper In Lipid Metabolism Atherosclerosis and Inflammationmentioning

confidence: 99%

Emerging roles of GPER in diabetes and atherosclerosis

Barton

Prossnitz

2015

Trends in Endocrinology & Metabolism

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G protein-coupled estrogen receptor (GPER) is a 7-transmembrane receptor implicated in rapid estrogen signaling. Originally cloned from vascular endothelial cells, GPER plays a central role in the regulation of vascular tone and cell growth, as well as lipid and glucose homeostasis. This review highlights our knowledge of the physiological and pathophysiological functions of GPER in the pancreas, peripheral and immune tissues, and the arterial vasculature. Recent findings of its roles in obesity, diabetes, and atherosclerosis, including the GPER-dependent regulation of lipid metabolism and inflammation, are presented. The therapeutic potential of targeting GPER-dependent pathways in chronic diseases such as coronary artery disease and diabetes and in the context of menopause is also discussed.

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“…Differences in MAP were ascribed to a lack of increase in lumen circumference in mesenteric resistance vessels of older GPER KO2 mice, suggesting a deficit in vessel diameter growth in GPER KO2 mice with age. Reports have also described that male, but not female, GPR30 KO3 or GPER-LacZ mice exhibit either impaired left ventricular cardiac function with enlarged left ventricles displaying both impaired contractility and relaxation [112] or decreased ejection fraction and fractional shortening, specifically in aging (male) mice [113]. …”

Section: Cardiovascular and Renal Functionsmentioning

confidence: 99%

“…Interestingly, at about the same time, Leeb-Lundberg and colleagues reported that female (but not male) GPER KO2 mice exhibited a ~10% decrease in body weight at 19 weeks of age, with a similar decrease in overall body size [50], whereas Otto and colleagues observed no differences in body weight at 5 months of age in GPER KO3 mice [49]. Finally, Noppinger and colleagues reported that the overall body weight as well as lean and fat mass was unaltered in GPER-LacZ fusion mice [51], although female GPER-LacZ mice fed a high-fat diet exhibited lower HDL levels and excess fat accumulation in the liver [113]. Some of these apparent discrepancies may be due to the age of the mice studied, targeting strategy, genetic background, diet or possibly environmental factors.…”

Section: Metabolic Functions: Obesity and Diabetesmentioning

confidence: 99%

What have we learned about GPER function in physiology and disease from knockout mice?

Prossnitz

Hathaway

2015

The Journal of Steroid Biochemistry and Molecular Biology

125

106

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Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and patho-physiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also revealed roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer.

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Sex- and age-dependent effects of Gpr30 genetic deletion on the metabolic and cardiovascular profiles of diet-induced obese mice

Cited by 39 publications

References 63 publications

GPER–novel membrane oestrogen receptor

GPER–novel membrane oestrogen receptor

Emerging roles of GPER in diabetes and atherosclerosis

What have we learned about GPER function in physiology and disease from knockout mice?

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