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

CH Profiles and Lipoprotein Analyses of the Plasma of the SYN and LERKO FemalesPlasma was obtained from SYN and LERKO females at 3 months of age euthanized at different phases of the estrous cycle or 30 days after OVX.(A) Representative profile of the total CH content (expressed as milligrams per deciliters) in the fractions of plasma separated by FPLC. The experiment was repeated three times with six different animals in each experimental group.(B and C) Western blot for apo-AI (B) and apo-E (C) in the FPLC fractions of the plasma at P and E.(D) Sizes of HDLs (d = 1.063–1.21 g/ml) purified by sequential ultracentrifugation from pooled plasma samples. The data indicate mean ± SEM; n = 3 pools of plasma (each pool was composed of the plasma of six mice).(E) Real-time PCR quantitative analyses of the liver mRNA contents of Pltp (top) and Lipc (bottom). The data indicate mean ± SEM; n = 6. The experiment was repeated twice.(F) CEC as measured by radioisotopic assay in J774 cells pre-radiolabeled with 3H-CH and incubated with plasma from either SYN or LERKO females at P or E. The data are expressed as the percentage of the radioactivity released into the medium over the total radioactivity incorporated by the cells. The data indicate mean ± SEM; n = 10.∗p < 0.05 and ∗∗∗p < 0.001 versus SYN 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

fig3: CH Profiles and Lipoprotein Analyses of the Plasma of the SYN and LERKO FemalesPlasma was obtained from SYN and LERKO females at 3 months of age euthanized at different phases of the estrous cycle or 30 days after OVX.(A) Representative profile of the total CH content (expressed as milligrams per deciliters) in the fractions of plasma separated by FPLC. The experiment was repeated three times with six different animals in each experimental group.(B and C) Western blot for apo-AI (B) and apo-E (C) in the FPLC fractions of the plasma at P and E.(D) Sizes of HDLs (d = 1.063–1.21 g/ml) purified by sequential ultracentrifugation from pooled plasma samples. The data indicate mean ± SEM; n = 3 pools of plasma (each pool was composed of the plasma of six mice).(E) Real-time PCR quantitative analyses of the liver mRNA contents of Pltp (top) and Lipc (bottom). The data indicate mean ± SEM; n = 6. The experiment was repeated twice.(F) CEC as measured by radioisotopic assay in J774 cells pre-radiolabeled with 3H-CH and incubated with plasma from either SYN or LERKO females at P or E. The data are expressed as the percentage of the radioactivity released into the medium over the total radioactivity incorporated by the cells. The data indicate mean ± SEM; n = 10.∗p < 0.05 and ∗∗∗p < 0.001 versus SYN at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.

Mentions: CH distribution among plasma lipoproteins was analyzed by fast protein liquid chromatography (FPLC). Figure 3A shows that, in the SYN mice, the CH-lipoprotein profile was very reproducible across all phases of the estrous cycle, with the exception of P, in which we observed a significant delay in the elution of the HDL peak. Indeed, in the plasma of the SYN mice at E, M, and D, CH eluted in fractions 31–33, whereas at P, the CH eluted in fractions 36–38. This observation suggested that the HDLs were smaller during P. This phenomenon was not observed in the plasma of the LERKO mutants, in which the FPLC profiles of the HDLs were the same in all the phases of the cycle and were superimposable to those of the SYN mice at E, M, and D. These findings provided evidence for the involvement of liver ERα in the generation of a distinct class of HDLs during P (when the circulating estrogens were the highest) and led us to investigate the consequences of OVX. In OVX mice, CH was present in the HDLs (eluting in fractions 31–33) and in the other classes of lipoproteins (very low-density lipoprotein [VLDL] and LDL), showing a CH profile similar to that of E (the phase of the estrous cycle with the lowest concentration of estrogens).


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)

CH Profiles and Lipoprotein Analyses of the Plasma of the SYN and LERKO FemalesPlasma was obtained from SYN and LERKO females at 3 months of age euthanized at different phases of the estrous cycle or 30 days after OVX.(A) Representative profile of the total CH content (expressed as milligrams per deciliters) in the fractions of plasma separated by FPLC. The experiment was repeated three times with six different animals in each experimental group.(B and C) Western blot for apo-AI (B) and apo-E (C) in the FPLC fractions of the plasma at P and E.(D) Sizes of HDLs (d = 1.063–1.21 g/ml) purified by sequential ultracentrifugation from pooled plasma samples. The data indicate mean ± SEM; n = 3 pools of plasma (each pool was composed of the plasma of six mice).(E) Real-time PCR quantitative analyses of the liver mRNA contents of Pltp (top) and Lipc (bottom). The data indicate mean ± SEM; n = 6. The experiment was repeated twice.(F) CEC as measured by radioisotopic assay in J774 cells pre-radiolabeled with 3H-CH and incubated with plasma from either SYN or LERKO females at P or E. The data are expressed as the percentage of the radioactivity released into the medium over the total radioactivity incorporated by the cells. The data indicate mean ± SEM; n = 10.∗p < 0.05 and ∗∗∗p < 0.001 versus SYN 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

fig3: CH Profiles and Lipoprotein Analyses of the Plasma of the SYN and LERKO FemalesPlasma was obtained from SYN and LERKO females at 3 months of age euthanized at different phases of the estrous cycle or 30 days after OVX.(A) Representative profile of the total CH content (expressed as milligrams per deciliters) in the fractions of plasma separated by FPLC. The experiment was repeated three times with six different animals in each experimental group.(B and C) Western blot for apo-AI (B) and apo-E (C) in the FPLC fractions of the plasma at P and E.(D) Sizes of HDLs (d = 1.063–1.21 g/ml) purified by sequential ultracentrifugation from pooled plasma samples. The data indicate mean ± SEM; n = 3 pools of plasma (each pool was composed of the plasma of six mice).(E) Real-time PCR quantitative analyses of the liver mRNA contents of Pltp (top) and Lipc (bottom). The data indicate mean ± SEM; n = 6. The experiment was repeated twice.(F) CEC as measured by radioisotopic assay in J774 cells pre-radiolabeled with 3H-CH and incubated with plasma from either SYN or LERKO females at P or E. The data are expressed as the percentage of the radioactivity released into the medium over the total radioactivity incorporated by the cells. The data indicate mean ± SEM; n = 10.∗p < 0.05 and ∗∗∗p < 0.001 versus SYN at P; #p < 0.05, ##p < 0.01, and ###p < 0.001 versus SYN.
Mentions: CH distribution among plasma lipoproteins was analyzed by fast protein liquid chromatography (FPLC). Figure 3A shows that, in the SYN mice, the CH-lipoprotein profile was very reproducible across all phases of the estrous cycle, with the exception of P, in which we observed a significant delay in the elution of the HDL peak. Indeed, in the plasma of the SYN mice at E, M, and D, CH eluted in fractions 31–33, whereas at P, the CH eluted in fractions 36–38. This observation suggested that the HDLs were smaller during P. This phenomenon was not observed in the plasma of the LERKO mutants, in which the FPLC profiles of the HDLs were the same in all the phases of the cycle and were superimposable to those of the SYN mice at E, M, and D. These findings provided evidence for the involvement of liver ERα in the generation of a distinct class of HDLs during P (when the circulating estrogens were the highest) and led us to investigate the consequences of OVX. In OVX mice, CH was present in the HDLs (eluting in fractions 31–33) and in the other classes of lipoproteins (very low-density lipoprotein [VLDL] and LDL), showing a CH profile similar to that of E (the phase of the estrous cycle with the lowest concentration of estrogens).

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