The estrogen receptor-α is required and sufficient to maintain physiological glucose uptake in the mouse heart.
Estrogens attenuate cardiac hypertrophy and increase cardiac contractility via their cognate estrogen receptors (ERs) ERα and ERβ. Because female sex hormones enhance global glucose use and because myocardial function and mass are tightly linked to cardiac glucose metabolism, we tested the hypothesis that expression and activation of the ERα might be required and sufficient to maintain physiological cardiac glucose uptake in the murine heart. Cardiac glucose uptake quantified in vivo by 18F-fluorodeoxyglucose positron emission tomography was strongly impaired in ovariectomized compared with gonadal intact female C57BL/6JO mice. The selective ERα agonist 16α-LE2 and the nonselective ERα and ERβ agonist 17β-estradiol completely restored cardiac glucose uptake in ovariectomized mice. Cardiac 18F-fluorodeoxyglucose uptake was strongly decreased in female ERα knockout mice compared with wild-type littermates. Analysis of cardiac mRNA accumulation by quantitative RT-PCR revealed an upregulation of genes involved in glycolisis and tricarboxylic acid cycle by ERα treatment. In conclusion, systemic activation of ERα is sufficient, and its expression is required to maintain physiological glucose uptake in the murine heart, which is likely to contribute to known cardioprotective estrogen effects.
Department of Internal Medicine, University of Wuerzburg, Oberduerrbacher Str 6, D-97080 Wuerzburg, Germany.
Paula-Anahi
PA
Arias-Loza
Michael C
MC
Kreissl
Susanne
S
Kneitz
Franz R
FR
Kaiser
Ina
I
Israel
Kai
K
Hu
Stefan
S
Frantz
Barbara
B
Bayer
Karl-Heinz
KH
Fritzemeier
Kenneth S
KS
Korach
Theo
T
Pelzer
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D007328:Insulin / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D010052:Ovariectomy
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D007328:Insulin; D004958:Estradiol; D005947:Glucose