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Estrogen signaling in metabolic inflammation.

Monteiro R, Teixeira D, Calhau C - Mediators Inflamm. (2014)

Bottom Line: However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties.In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field.Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, Medical Investigation Center, 4200-319 Porto, Portugal.

ABSTRACT
There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

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Related in: MedlinePlus

Estrogen metabolism. The effects of experimental manipulation of enzymes marked in grey boxes modulation are highlighted. Inactivation of aromatase leads to metabolic dysfunction that can be reversed by estrogen replacement. In opposite, estrogen sulfotransferase inactivation in models of obesity or type 2 diabetes mellitus improves metabolic function, an effect that is abolished by ovariectomy. Hepatic expression of steroid sulfatase is induced in animal models of obesity and type 2 diabetes mellitus and seems to alleviate dysmetabolic changes; this effect is also lost with ovariectomy. 17Beta-HSD, 17beta-hydroxysteroid dehydrogenase.
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fig1: Estrogen metabolism. The effects of experimental manipulation of enzymes marked in grey boxes modulation are highlighted. Inactivation of aromatase leads to metabolic dysfunction that can be reversed by estrogen replacement. In opposite, estrogen sulfotransferase inactivation in models of obesity or type 2 diabetes mellitus improves metabolic function, an effect that is abolished by ovariectomy. Hepatic expression of steroid sulfatase is induced in animal models of obesity and type 2 diabetes mellitus and seems to alleviate dysmetabolic changes; this effect is also lost with ovariectomy. 17Beta-HSD, 17beta-hydroxysteroid dehydrogenase.

Mentions: Estrogens are synthesized by aromatase, a cytochrome P450 enzyme located in the endoplasmic reticulum of estrogen producing cells which catalyzes the aromatization of testosterone and androstenedione [30], to 17beta-estradiol, the most active estrogen, and estrone, respectively [31]. In humans, estrogens are generated in several tissues including the ovaries, testis, placenta, fetal but not adult liver, bone chondrocytes and osteoblasts, vascular smooth muscle cells, skin, skeletal muscle, several brain regions, and the AT [30, 32, 33]. The gonads and the adrenals express all the necessary enzymes to synthesize estrogens from cholesterol whereas other tissues, such as the bone or the AT, depend on precursor supply from those organs through the blood [34]. In peripheral tissues, 17beta-hydroxysteroid dehydrogenase (17beta-HSD) converts the weaker hormones androstenedione and estrone to stronger ones, testosterone and 17beta-estradiol, respectively (Figure 1) [35, 36].


Estrogen signaling in metabolic inflammation.

Monteiro R, Teixeira D, Calhau C - Mediators Inflamm. (2014)

Estrogen metabolism. The effects of experimental manipulation of enzymes marked in grey boxes modulation are highlighted. Inactivation of aromatase leads to metabolic dysfunction that can be reversed by estrogen replacement. In opposite, estrogen sulfotransferase inactivation in models of obesity or type 2 diabetes mellitus improves metabolic function, an effect that is abolished by ovariectomy. Hepatic expression of steroid sulfatase is induced in animal models of obesity and type 2 diabetes mellitus and seems to alleviate dysmetabolic changes; this effect is also lost with ovariectomy. 17Beta-HSD, 17beta-hydroxysteroid dehydrogenase.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4226184&req=5

fig1: Estrogen metabolism. The effects of experimental manipulation of enzymes marked in grey boxes modulation are highlighted. Inactivation of aromatase leads to metabolic dysfunction that can be reversed by estrogen replacement. In opposite, estrogen sulfotransferase inactivation in models of obesity or type 2 diabetes mellitus improves metabolic function, an effect that is abolished by ovariectomy. Hepatic expression of steroid sulfatase is induced in animal models of obesity and type 2 diabetes mellitus and seems to alleviate dysmetabolic changes; this effect is also lost with ovariectomy. 17Beta-HSD, 17beta-hydroxysteroid dehydrogenase.
Mentions: Estrogens are synthesized by aromatase, a cytochrome P450 enzyme located in the endoplasmic reticulum of estrogen producing cells which catalyzes the aromatization of testosterone and androstenedione [30], to 17beta-estradiol, the most active estrogen, and estrone, respectively [31]. In humans, estrogens are generated in several tissues including the ovaries, testis, placenta, fetal but not adult liver, bone chondrocytes and osteoblasts, vascular smooth muscle cells, skin, skeletal muscle, several brain regions, and the AT [30, 32, 33]. The gonads and the adrenals express all the necessary enzymes to synthesize estrogens from cholesterol whereas other tissues, such as the bone or the AT, depend on precursor supply from those organs through the blood [34]. In peripheral tissues, 17beta-hydroxysteroid dehydrogenase (17beta-HSD) converts the weaker hormones androstenedione and estrone to stronger ones, testosterone and 17beta-estradiol, respectively (Figure 1) [35, 36].

Bottom Line: However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties.In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field.Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, Medical Investigation Center, 4200-319 Porto, Portugal.

ABSTRACT
There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

Show MeSH
Related in: MedlinePlus