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An Essential Role for Liver ERα in Coupling Hepatic Metabolism to the Reproductive Cycle.

Della Torre S, Mitro N, Fontana R, Gomaraschi M, Favari E, Recordati C, Lolli F, Quagliarini F, Meda C, Ohlsson C, Crestani M, Uhlenhaut NH, Calabresi L, Maggi A - Cell Rep (2016)

Bottom Line: We show that this receptor regulates the synthesis of cholesterol transport proteins, enzymes for lipoprotein remodeling, and receptors for cholesterol uptake.Additionally, ERα is indispensable during proestrus for the generation of high-density lipoproteins efficient in eliciting cholesterol efflux from macrophages.We propose that a specific interaction with liver X receptor α (LXRα) mediates the broad effects of ERα on the hepatic lipid metabolism.

View Article: PubMed Central - PubMed

Affiliation: Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.

No MeSH data available.


Related in: MedlinePlus

Effect of Estrous Cycle Progression on Liver CH Metabolism in the SYN and LERKO Female MiceLiver extracts were obtained from the livers of 3-month-old female mice.(A–C) Total CH content (A). Free CH (B) and CE (C) content expressed as a percentage of the total CH. The data indicate mean ± SEM; n = 10.(D) BA content measured in the feces. The data indicate mean ± SEM; n = 10.(E and F) TG (E) and FFA (F) liver contents. The data indicate mean ± SEM; n = 5.(G) Representative western blotting analyses of the contents of apo-AI, apo-E, SR-B1, and LDLR in liver extracts.(H) Semiquantitative analyses of blotting with antibodies anti-apo-AI, -apo-E, -SR-B1, and -LDLR. The data indicate mean ± SEM of six animals. The experiment was repeated twice.∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; OOp < 0.01 versus LERKO at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.
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fig2: Effect of Estrous Cycle Progression on Liver CH Metabolism in the SYN and LERKO Female MiceLiver extracts were obtained from the livers of 3-month-old female mice.(A–C) Total CH content (A). Free CH (B) and CE (C) content expressed as a percentage of the total CH. The data indicate mean ± SEM; n = 10.(D) BA content measured in the feces. The data indicate mean ± SEM; n = 10.(E and F) TG (E) and FFA (F) liver contents. The data indicate mean ± SEM; n = 5.(G) Representative western blotting analyses of the contents of apo-AI, apo-E, SR-B1, and LDLR in liver extracts.(H) Semiquantitative analyses of blotting with antibodies anti-apo-AI, -apo-E, -SR-B1, and -LDLR. The data indicate mean ± SEM of six animals. The experiment was repeated twice.∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; OOp < 0.01 versus LERKO at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.

Mentions: The following series of findings in female mouse liver indicated a tight coupling between the reproductive cycle and CH metabolism (Figure 2): total CH content oscillated with the estrous cycle, and free/total CH was the lowest during diestrus (D); in this phase of the cycle, the ratio between cholesteryl esters (CEs) and total CH was the highest. CH catabolism was also regulated as indicated by measurements of bile acid (BA) contents in the feces, which were lower at estrus (E) and M than at P and D. These changes were not observed in the LERKO mice, which led to the conclusion that, in the absence of liver ERα, hepatic CH metabolism and ovarian activity are uncoupled (Figures 2A–2D).


An Essential Role for Liver ERα in Coupling Hepatic Metabolism to the Reproductive Cycle.

Della Torre S, Mitro N, Fontana R, Gomaraschi M, Favari E, Recordati C, Lolli F, Quagliarini F, Meda C, Ohlsson C, Crestani M, Uhlenhaut NH, Calabresi L, Maggi A - Cell Rep (2016)

Effect of Estrous Cycle Progression on Liver CH Metabolism in the SYN and LERKO Female MiceLiver extracts were obtained from the livers of 3-month-old female mice.(A–C) Total CH content (A). Free CH (B) and CE (C) content expressed as a percentage of the total CH. The data indicate mean ± SEM; n = 10.(D) BA content measured in the feces. The data indicate mean ± SEM; n = 10.(E and F) TG (E) and FFA (F) liver contents. The data indicate mean ± SEM; n = 5.(G) Representative western blotting analyses of the contents of apo-AI, apo-E, SR-B1, and LDLR in liver extracts.(H) Semiquantitative analyses of blotting with antibodies anti-apo-AI, -apo-E, -SR-B1, and -LDLR. The data indicate mean ± SEM of six animals. The experiment was repeated twice.∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; OOp < 0.01 versus LERKO at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835581&req=5

fig2: Effect of Estrous Cycle Progression on Liver CH Metabolism in the SYN and LERKO Female MiceLiver extracts were obtained from the livers of 3-month-old female mice.(A–C) Total CH content (A). Free CH (B) and CE (C) content expressed as a percentage of the total CH. The data indicate mean ± SEM; n = 10.(D) BA content measured in the feces. The data indicate mean ± SEM; n = 10.(E and F) TG (E) and FFA (F) liver contents. The data indicate mean ± SEM; n = 5.(G) Representative western blotting analyses of the contents of apo-AI, apo-E, SR-B1, and LDLR in liver extracts.(H) Semiquantitative analyses of blotting with antibodies anti-apo-AI, -apo-E, -SR-B1, and -LDLR. The data indicate mean ± SEM of six animals. The experiment was repeated twice.∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; OOp < 0.01 versus LERKO at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.
Mentions: The following series of findings in female mouse liver indicated a tight coupling between the reproductive cycle and CH metabolism (Figure 2): total CH content oscillated with the estrous cycle, and free/total CH was the lowest during diestrus (D); in this phase of the cycle, the ratio between cholesteryl esters (CEs) and total CH was the highest. CH catabolism was also regulated as indicated by measurements of bile acid (BA) contents in the feces, which were lower at estrus (E) and M than at P and D. These changes were not observed in the LERKO mice, which led to the conclusion that, in the absence of liver ERα, hepatic CH metabolism and ovarian activity are uncoupled (Figures 2A–2D).

Bottom Line: We show that this receptor regulates the synthesis of cholesterol transport proteins, enzymes for lipoprotein remodeling, and receptors for cholesterol uptake.Additionally, ERα is indispensable during proestrus for the generation of high-density lipoproteins efficient in eliciting cholesterol efflux from macrophages.We propose that a specific interaction with liver X receptor α (LXRα) mediates the broad effects of ERα on the hepatic lipid metabolism.

View Article: PubMed Central - PubMed

Affiliation: Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.

No MeSH data available.


Related in: MedlinePlus