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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

Liver Histology and Measurement of Esr1 Expression in the SYN and LERKO Mice(A) Liver histology. Top: H&E staining; the black arrows highlight hepatocellular vacuolar degeneration. Center: oil red O staining plus H&E (neutral fats are stained orange red, and the nuclei are shown in blue). Bottom: Masson’s trichrome staining with aberrant collagen deposits (blue); the hepatocyte cytoplasm is red, and the nuclei are dark red-black structures within cells. For both SYN and LERKO: scale bar for left columns, 33 μm; scale bar for right columns, 10.6 μm.(B) Quantitative analysis of Esr1 mRNA in the livers of 3-month-old cycling females measured by real-time PCR; OVX for 30 days and age-matched males. The data indicate mean ± SEM; n = 6 ÷ 12; the experiment was repeated three times.(C) Representative western blot and semiquantitative analysis of ERα protein in liver extracts. The data indicate mean ± SEM; n = 5. The experiment was repeated three times.∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; ##p < 0.01 and ###p < 0.001 versus SYN.
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fig1: Liver Histology and Measurement of Esr1 Expression in the SYN and LERKO Mice(A) Liver histology. Top: H&E staining; the black arrows highlight hepatocellular vacuolar degeneration. Center: oil red O staining plus H&E (neutral fats are stained orange red, and the nuclei are shown in blue). Bottom: Masson’s trichrome staining with aberrant collagen deposits (blue); the hepatocyte cytoplasm is red, and the nuclei are dark red-black structures within cells. For both SYN and LERKO: scale bar for left columns, 33 μm; scale bar for right columns, 10.6 μm.(B) Quantitative analysis of Esr1 mRNA in the livers of 3-month-old cycling females measured by real-time PCR; OVX for 30 days and age-matched males. The data indicate mean ± SEM; n = 6 ÷ 12; the experiment was repeated three times.(C) Representative western blot and semiquantitative analysis of ERα protein in liver extracts. The data indicate mean ± SEM; n = 5. The experiment was repeated three times.∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; ##p < 0.01 and ###p < 0.001 versus SYN.

Mentions: The effects of liver Esr1 ablation were initially studied in fertile females euthanized at 10 months of age. The livers of syngenic (SYN) and LERKO mice were dissected for morphological examination based on a combination of staining procedures (Figure 1A; Table S1). H&E staining revealed a variable degree (from mild to marked) of hepatocellular vacuolar degeneration. Although overt effects of Esr1 ablation were not immediately evident, in the LERKO mice, the vacuolization was slightly more marked, which was suggestive of changes in fat deposits. Such changes were further suggested by the observation that, overall, the oil-red-O-stained lipid droplets were larger in the LERKO than in the SYN mice and that Masson’s trichrome staining of the LERKO livers revealed portal infiltration of mononuclear leukocytes and portal or centrilobular collagen deposition. Quantitative analyses demonstrated that the livers of the LERKO mice exhibited increased oil red O staining (+112%; Figure S1; Table S1) and a greater expression of genes involved in the inflammatory process and collagen deposition (Figure S2).


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)

Liver Histology and Measurement of Esr1 Expression in the SYN and LERKO Mice(A) Liver histology. Top: H&E staining; the black arrows highlight hepatocellular vacuolar degeneration. Center: oil red O staining plus H&E (neutral fats are stained orange red, and the nuclei are shown in blue). Bottom: Masson’s trichrome staining with aberrant collagen deposits (blue); the hepatocyte cytoplasm is red, and the nuclei are dark red-black structures within cells. For both SYN and LERKO: scale bar for left columns, 33 μm; scale bar for right columns, 10.6 μm.(B) Quantitative analysis of Esr1 mRNA in the livers of 3-month-old cycling females measured by real-time PCR; OVX for 30 days and age-matched males. The data indicate mean ± SEM; n = 6 ÷ 12; the experiment was repeated three times.(C) Representative western blot and semiquantitative analysis of ERα protein in liver extracts. The data indicate mean ± SEM; n = 5. The experiment was repeated three times.∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; ##p < 0.01 and ###p < 0.001 versus SYN.
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fig1: Liver Histology and Measurement of Esr1 Expression in the SYN and LERKO Mice(A) Liver histology. Top: H&E staining; the black arrows highlight hepatocellular vacuolar degeneration. Center: oil red O staining plus H&E (neutral fats are stained orange red, and the nuclei are shown in blue). Bottom: Masson’s trichrome staining with aberrant collagen deposits (blue); the hepatocyte cytoplasm is red, and the nuclei are dark red-black structures within cells. For both SYN and LERKO: scale bar for left columns, 33 μm; scale bar for right columns, 10.6 μm.(B) Quantitative analysis of Esr1 mRNA in the livers of 3-month-old cycling females measured by real-time PCR; OVX for 30 days and age-matched males. The data indicate mean ± SEM; n = 6 ÷ 12; the experiment was repeated three times.(C) Representative western blot and semiquantitative analysis of ERα protein in liver extracts. The data indicate mean ± SEM; n = 5. The experiment was repeated three times.∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 versus SYN at P; ##p < 0.01 and ###p < 0.001 versus SYN.
Mentions: The effects of liver Esr1 ablation were initially studied in fertile females euthanized at 10 months of age. The livers of syngenic (SYN) and LERKO mice were dissected for morphological examination based on a combination of staining procedures (Figure 1A; Table S1). H&E staining revealed a variable degree (from mild to marked) of hepatocellular vacuolar degeneration. Although overt effects of Esr1 ablation were not immediately evident, in the LERKO mice, the vacuolization was slightly more marked, which was suggestive of changes in fat deposits. Such changes were further suggested by the observation that, overall, the oil-red-O-stained lipid droplets were larger in the LERKO than in the SYN mice and that Masson’s trichrome staining of the LERKO livers revealed portal infiltration of mononuclear leukocytes and portal or centrilobular collagen deposition. Quantitative analyses demonstrated that the livers of the LERKO mice exhibited increased oil red O staining (+112%; Figure S1; Table S1) and a greater expression of genes involved in the inflammatory process and collagen deposition (Figure S2).

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