17β-Estradiol attenuates saturated fatty acid diet-induced liver injury in ovariectomized mice by up-regulating hepatic senescence marker protein-30
Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 11/2011; 415(2):252-7. DOI: 10.1016/j.bbrc.2011.10.025
Senescence marker protein-30 (SMP30) plays an important role in intracellular Ca(2+) homeostasis. The aim of the present study was to investigate the effects of estrogens on liver apoptotic damage and changes in SMP30 expression induced by a high saturated fatty acid diet (HSFD). Ovariectomized mice (OVX) and sham-operated mice (SHAM) were randomly divided into five groups: SHAM fed a normal diet (SHAM/ND), SHAM fed HSFD (SHAM/HSFD), OVX fed ND (OVX/ND), OVX fed HSFD (OVX/HSFD) and OVX fed HSFD with 17β-estradiol (E2) supplementation using an implanted slow-release pellet (OVX/HSFD+E2). After 8 weeks, markers of endoplasmic reticulum (ER) stress and apoptosis, and levels of tumor necrosis factor-α (TNFα and SMP30 expression were investigated. Compared with SHAM/ND, OVX/HSFD mice showed significantly increased spliced X-box protein-1 (s-XBP1), phosphorylated eukaryotic initiation factor-2α (p-eIF2α), glucose-regulated protein 78 (GPR78), C/EBP homologous protein (CHOP), cytosolic cytochrome c, caspase-3 activity, and TNFα, and significantly decreased SMP30. These differences in OVX/HSFD mice were restored to the levels of SHAM/ND mice by E2 supplementation. These results suggest that E2 supplementation attenuates HSFD-induced liver apoptotic death in ovariectomized mice by up-regulating SMP30.
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ABSTRACT: Objective: Although low serum testosterone (T) is associated with metabolic disorders, the mechanism of this association is unclear. The objective of the present study was to investigate the combined effects of T deficiency and a high-fat diet (HFD) on hepatic lipid homeostasis in mice. Materials/methods: Orchiectomized (ORX) mice and sham-operated (SHAM) mice were randomly divided into five groups: SHAM mice fed a standard diet (SD), SHAM mice fed HFD, ORX mice fed SD, ORX mice fed HFD, and ORX mice fed HFD with T supplementation. After 4weeks of treatment, we investigated the synthesis and secretion of lipids in the liver and detailed serum lipoprotein profiles in each group. Results: ORX mice fed HFD showed increased hepatic steatosis, markedly decreased serum triglyceride (TG) and TG-VLDL content, and increased serum very small-LDL content. Gene expression analysis revealed that ORX mice fed HFD showed significantly decreased expression of microsomal triglyceride transfer protein, lipin-1, peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ coactivator 1-α, and significantly increased sterol regulatory element-binding protein-1, diacylglycerol acyltransferase-2 and fatty acid synthase. Reduction of hepatic AMPK phosphorylation was observed in ORX mice fed HFD. These perturbations in ORX mice fed HFD were normalized to the levels of SHAM mice fed HFD by T supplementation. Conclusion: T deficiency is associated with failure of lipid homeostasis mediated by altered expression of genes involved in hepatic assembly and secretion of lipids.Metabolism: clinical and experimental 01/2013; 62(6). DOI:10.1016/j.metabol.2012.12.007 · 3.89 Impact Factor
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ABSTRACT: It is well established that estrogen deficiency is strongly linked to the development of insulin resistance (IR), but the mechanism is still unclear. Since IR is characterized by a marked reduction in insulin-stimulated PI3 K-mediated activation of Akt in liver and skeletal muscle, we hypothesized that ovariectomized rats (OVX) would exhibit reductions in the expression of proteins in PI3 K signaling pathway, including PI3 K and Akt. As hypothesized, after observing for 12 weeks, compared with the SHAM rats, ovariectomy led to decreased plasma estrogen level and increased HOMA-IR index; in addition, ovariectomy also caused decreased PI3 K and Akt expression levels in the liver and skeletal muscle. Interestingly, the expression patterns differed in tissue-dependent fashion: Akt1 was only found reduction in liver, whereas Akt2 decreased in muscle; these changes can be reversed by estrogen supplement (OVXE). In conclusion, data demonstrate that estrogen withdrawals may cause IR at least in part by impaired PI3 K/Akt signaling proteins in liver and skeletal muscle, and Akt1 and Akt2 might be tissue-specific expressions.Endocrine 02/2013; 44(3). DOI:10.1007/s12020-013-9894-1 · 3.88 Impact Factor
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ABSTRACT: Regucalcin (RGN) is a calcium (Ca(2+))-binding protein widely expressed in vertebrate and invertebrate species, which is also known as senescence marker protein 30, due to its molecular weight (33 kDa) and a characteristically diminished expression with the aging process. RGN regulates intracellular Ca(2+) homeostasis and the activity of several proteins involved in intracellular signalling pathways, namely, kinases, phosphatases, phosphodiesterase, nitric oxide synthase and proteases, which highlights its importance in cell biology. In addition, RGN has cytoprotective effects reducing intracellular levels of oxidative stress, also playing a role in the control of cell survival and apoptosis. Multiple factors have been identified regulating the cell levels of RGN transcripts and protein, and an altered expression pattern of this interesting protein has been found in cases of reproductive disorders, neurodegenerative diseases and cancer. Moreover, RGN is a serum-secreted protein, and its levels have been correlated with the stage of disease, which strongly suggests the usefulness of this protein as a potential biomarker for monitoring disease onset and progression. The present review aims to discuss the available information concerning RGN expression and function in distinct cell types and tissues, integrating cellular and molecular mechanisms in the context of normal and pathological conditions. Insight into the cellular actions of RGN will be a key step towards deepening the knowledge of the biology of several human diseases.Cellular and Molecular Life Sciences CMLS 03/2013; 71(1). DOI:10.1007/s00018-013-1323-3 · 5.81 Impact Factor
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