Limits...
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 the Estrous Cycle on PPARα and LXRα Syntheses and Transcriptional Activities(A) The PPARα mRNA (top) and protein (bottom) liver contents were measured by real-time PCR and western blot analysis.(B) Real-time PCR quantitative analyses of the PPARα target genes Cpt1α, Hahdα, Acox, and Acsl1.(C) mRNA (top) and protein (bottom) of LXRα contents in liver homogenates from the SYN and LERKO mice.(D) The mRNA contents of the LXRα target genes Abcg5, Abca1, Cyp7a1, Cyp27a1, Shp, and Srebp-1c.For all of the real-time PCR analyses, the data indicate mean ± SEM, n = 6. The experiments were repeated three times. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; Op < 0.05, OOp < 0.01, and OOOp < 0.001 versus LERKO at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835581&req=5

fig4: Effect of the Estrous Cycle on PPARα and LXRα Syntheses and Transcriptional Activities(A) The PPARα mRNA (top) and protein (bottom) liver contents were measured by real-time PCR and western blot analysis.(B) Real-time PCR quantitative analyses of the PPARα target genes Cpt1α, Hahdα, Acox, and Acsl1.(C) mRNA (top) and protein (bottom) of LXRα contents in liver homogenates from the SYN and LERKO mice.(D) The mRNA contents of the LXRα target genes Abcg5, Abca1, Cyp7a1, Cyp27a1, Shp, and Srebp-1c.For all of the real-time PCR analyses, the data indicate mean ± SEM, n = 6. The experiments were repeated three times. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; Op < 0.05, OOp < 0.01, and OOOp < 0.001 versus LERKO at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.

Mentions: Previously, two ligand-dependent transcription factors, peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptor alpha (LXRα), have been found to act in the liver as the major nutritional sensors and key transcriptional modulators of lipid and carbohydrate metabolism (Bocher et al., 2002, Li and Glass, 2004, Zhang et al., 2012). This led us to ask whether ERα had any effect on the synthesis or activity of these two receptors. No changes in PPARα mRNA or protein contents were observed in the different phases of the reproductive cycle (Figure 4A). Similarly, no changes in the activity of PPARα were attributable to the progression of the estrous cycle, because the liver contents of PPARα target genes, such as carnitine palmitoyltransferase 1A (Cpt1α), hydroxyacyl-coenzyme A (CoA) dehydrogenase α (Hadhα), acyl-CoA oxidase 1 (Acox), and acyl-CoA synthetase long-chain family member 1 (Acsl1), were the same in all phases of the cycle (Figure 4B). These results were replicated in the LERKO mice in which the expressions of PPARα and its target genes were superimposable with the patterns observed in the SYN mice. This suggested that the aforementioned effects reported of hepatic ERα on liver metabolism did not occur via PPARα.


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 the Estrous Cycle on PPARα and LXRα Syntheses and Transcriptional Activities(A) The PPARα mRNA (top) and protein (bottom) liver contents were measured by real-time PCR and western blot analysis.(B) Real-time PCR quantitative analyses of the PPARα target genes Cpt1α, Hahdα, Acox, and Acsl1.(C) mRNA (top) and protein (bottom) of LXRα contents in liver homogenates from the SYN and LERKO mice.(D) The mRNA contents of the LXRα target genes Abcg5, Abca1, Cyp7a1, Cyp27a1, Shp, and Srebp-1c.For all of the real-time PCR analyses, the data indicate mean ± SEM, n = 6. The experiments were repeated three times. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; Op < 0.05, OOp < 0.01, and OOOp < 0.001 versus LERKO at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835581&req=5

fig4: Effect of the Estrous Cycle on PPARα and LXRα Syntheses and Transcriptional Activities(A) The PPARα mRNA (top) and protein (bottom) liver contents were measured by real-time PCR and western blot analysis.(B) Real-time PCR quantitative analyses of the PPARα target genes Cpt1α, Hahdα, Acox, and Acsl1.(C) mRNA (top) and protein (bottom) of LXRα contents in liver homogenates from the SYN and LERKO mice.(D) The mRNA contents of the LXRα target genes Abcg5, Abca1, Cyp7a1, Cyp27a1, Shp, and Srebp-1c.For all of the real-time PCR analyses, the data indicate mean ± SEM, n = 6. The experiments were repeated three times. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; Op < 0.05, OOp < 0.01, and OOOp < 0.001 versus LERKO at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.
Mentions: Previously, two ligand-dependent transcription factors, peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptor alpha (LXRα), have been found to act in the liver as the major nutritional sensors and key transcriptional modulators of lipid and carbohydrate metabolism (Bocher et al., 2002, Li and Glass, 2004, Zhang et al., 2012). This led us to ask whether ERα had any effect on the synthesis or activity of these two receptors. No changes in PPARα mRNA or protein contents were observed in the different phases of the reproductive cycle (Figure 4A). Similarly, no changes in the activity of PPARα were attributable to the progression of the estrous cycle, because the liver contents of PPARα target genes, such as carnitine palmitoyltransferase 1A (Cpt1α), hydroxyacyl-coenzyme A (CoA) dehydrogenase α (Hadhα), acyl-CoA oxidase 1 (Acox), and acyl-CoA synthetase long-chain family member 1 (Acsl1), were the same in all phases of the cycle (Figure 4B). These results were replicated in the LERKO mice in which the expressions of PPARα and its target genes were superimposable with the patterns observed in the SYN mice. This suggested that the aforementioned effects reported of hepatic ERα on liver metabolism did not occur via PPARα.

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