Faculty Opinions recommendation of Estrogen Deficiency Promotes Hepatic Steatosis via a Glucocorticoid Receptor-Dependent Mechanism in Mice.

2018 ◽  
Author(s):  
E Ronald de Kloet ◽  
Jan Kroon ◽  
Onno Meijer
Keyword(s):  
Glucocorticoid Receptor ◽  
Hepatic Steatosis ◽  
Estrogen Deficiency ◽  
Dependent Mechanism

scholarly journals Estrogen Deficiency Promotes Hepatic Steatosis via a Glucocorticoid Receptor-Dependent Mechanism in Mice

Cell Reports ◽  
2018 ◽  
Vol 22 (10) ◽  
pp. 2690-2701 ◽  
Author(s):  
Matthew A. Quinn ◽  
Xiaojiang Xu ◽  
Melania Ronfani ◽  
John A. Cidlowski
Keyword(s):  
Glucocorticoid Receptor ◽  
Hepatic Steatosis ◽  
Estrogen Deficiency ◽  
Dependent Mechanism

scholarly journals Aromatase Deficiency Inhibits the Permeability Transition in Mouse Liver Mitochondria

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1643-1652 ◽  
Author(s):  
Loredana Moro ◽  
Arnaldo A. Arbini ◽  
Jer-Tsong Hsieh ◽  
Jeffery Ford ◽  
Evan R. Simpson ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Mitochondrial Permeability Transition ◽  
Adenine Nucleotide ◽  
Mitochondrial Protein ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Estrogen Deficiency ◽  
Mrna Levels ◽  
Mitochondrial Membranes ◽  
Mitochondrial Permeability

Lack of estrogens affects male physiology in a number of ways, including severe changes in liver metabolism that result in lipid accumulation and massive hepatic steatosis. Here we investigated whether estrogen deficiency may alter the functionality and permeability properties of liver mitochondria using, as an experimental model, aromatase knockout (ArKO) male mice, which cannot synthesize endogenous estrogens due to a disruption of the Cyp19 gene. Liver mitochondria isolated from ArKO mice displayed increased activity of the mitochondrial respiratory complex IV compared with wild-type mice and were less prone to undergo cyclosporin A-sensitive mitochondrial permeability transition (MPT) induced by calcium loading. The altered permeability properties of the mitochondrial membranes were not due to changes in reactive oxygen species, ATP levels, or mitochondrial membrane potential but were associated with increased content of the phospholipid cardiolipin, structural component of the mitochondrial membranes and regulator of the MPT pore, and with increased mitochondrial protein levels of Bcl-2 and the adenine nucleotide translocator (ANT), regulator and component of the MPT pore, respectively. Real-time RT-PCR demonstrated increased mRNA levels for Bcl-2 and ANT2 but not for the ANT1 isoform in ArKO livers. Supplementation of 17β-estradiol retrieved ArKO mice from massive hepatic steatosis and restored mitochondrial permeability properties, cardiolipin, Bcl-2, and ANT2 levels. Overall, our findings demonstrate an important role of estrogens in the modulation of hepatic mitochondrial function and permeability properties in males and suggest that estrogen deficiency may represent a novel positive regulator of Bcl-2 and ANT2 proteins, two inhibitors of MPT occurrence and powerful antiapoptotic molecules.

scholarly journals Quercitrin Ameliorates Hyperlipidemia and Hepatic Steatosis in Ovariectomized Mice

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 243
Author(s):  
Haeng Jeon Hur ◽  
Yeon-Hui Jeong ◽  
Sang Hee Lee ◽  
Mi Jeong Sung
Keyword(s):  
Lipid Metabolism ◽  
Postmenopausal Women ◽  
Hepatic Steatosis ◽  
Metabolic Diseases ◽  
Liver Lipid ◽  
Density Lipoprotein ◽  
Estrogen Deficiency ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Ovariectomized Mice

Nonalcoholic fatty liver disease (NAFLD) is associated with progressive metabolic diseases. Estrogen deficiency increases the NAFLD risk among postmenopausal women. Thus, effective agents to prevent and treat NAFLD in postmenopausal women are required. Quercitrin (Quer) is a natural glycosylated flavonoid with antimicrobial, anti-inflammatory, and hypolipidemic effects. This study investigated whether Quer improves dysregulated lipid metabolism and suppresses hepatic steatosis in ovariectomized (OVX) mice as an experimental model mimicking postmenopausal women. Mice were assigned to the following four groups: SHAM, OVX, OVX + β-estradiol (0.4 mg/kg diet), and OVX + Quer (500 mg/kg diet). Mice were administered a diet with or without Quer for three months. OVX mice displayed significantly higher body mass, epidermal fat, and liver weights than those of SHAM mice. However, these levels were reduced in Quer-treated mice. Quer treatment reduced the levels of serum lipid metabolites, including triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Furthermore, Quer reduced liver lipid steatosis and inhibited the expression of proinflammatory cytokines, such as tumor necrosis factor-α, IL-6, and IL-1β. The results of the present study indicate that Quer improves dysregulated lipid metabolism and reduces hepatic steatosis and inflammation by compensating for estrogen deficiency, suggesting that Quer may potentially exert protective effects during hepatic steatosis in postmenopausal women.

scholarly journals Resveratrol Ameliorates Lipid Droplet Accumulation in Liver Through a SIRT1/ ATF6-Dependent Mechanism

2018 ◽  
Vol 51 (5) ◽  
pp. 2397-2420 ◽  
Author(s):  
Rui Zhou ◽  
Long Yi ◽  
Xikun Ye ◽  
Xianglong Zeng ◽  
Kai Liu ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Neutral Lipids ◽  
Luciferase Reporter ◽  
Proximity Ligation Assay ◽  
Small Interfering Rnas ◽  
Expression Levels ◽  
Sirt1 Expression ◽  
Dependent Mechanism

Background/Aims: Lipid droplets (LDs) are dynamic organelles that store neutral lipids during times of energy excess, and an increased accumulation of LDs in the liver is closely linked to hepatic steatosis. Our previous studies suggested that resveratrol (RSV) supplement could improve hepatic steatosis, but the underlying mechanism, particularly which related to LD accumulation, has not yet been elucidated. Methods: A high-fat diet (HFD) and palmitic acid were used to induce hepatic steatosis in mouse liver and hepatocytes, respectively. The effects of RSV on LD accumulation were analyzed in vivo and in vitro. The effects of RSV on the expression levels of LD-associated genes (ATF6, Fsp27β/CIDEC, CREBH, and PLIN1) were measured by qRT-PCR and western blot assays, followed by KD or overexpression of SIRT1 and ATF6 with small interfering RNAs or overexpressed plasmids, respectively. The dual luciferase reporter assay, chromatin immunoprecipitation assay, coimmunoprecipitation, and proximity ligation assay were utilized to clarify the mechanism of transcriptional regulation and possible interaction between SIRT1 and ATF6. Results: There was a significant increase in the accumulation of LDs in liver and hepatocytes during the process of HFD-induced steatosis, respectively, which was significantly inhibited by RSV supplementation. RSV notably activated SIRT1 expression and decreased the expression levels of ATF6, Fsp27β/CIDEC, CREBH, and PLIN1, which are associated with LD accumulation. Interestingly, the inhibitory effects of RSV on LD accumulation and the associated expression of genes in hepatocytes were abrogated or strengthened with SIRT1 silencing or overexpression, respectively. On the contrary, the benefits of RSV in hepatocytes were eliminated or aggravated when transfected with the overexpressed ATF6 or ATF6 siRNA, respectively. Furthermore, we found that RSV stimulated SIRT1 expression significantly, which was followed by increased deacetylation and inactivation of ATF6, resulting in a positive feedback loop for SIRT1 transcription associated with ATF6 binding to the SIRT1 promoter region. Conclusion: Taken together, these findings indicate that RSV supplementation improves hepatic steatosis by ameliorating the accumulation of LDs, and this might be partially mediated by a SIRT1/ATF6-dependent mechanism.

scholarly journals Glucocorticoid Receptor β Induces Hepatic Steatosis by Augmenting Inflammation and Inhibition of the Peroxisome Proliferator-activated Receptor (PPAR) α

2016 ◽  
Vol 291 (50) ◽  
pp. 25776-25788 ◽  
Author(s):  
Joseph S. Marino ◽  
Lance A. Stechschulte ◽  
David E. Stec ◽  
Andrea Nestor-Kalinoski ◽  
Sydni Coleman ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Hepatic Steatosis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Su1795 Uric Acid Regulates Hepatic Steatosis and Insulin Resistance Through the NLRP3 Inflammasome Dependent Mechanism

2015 ◽  
Vol 148 (4) ◽  
pp. S-1053 ◽  
Author(s):  
Xingyong Wan ◽  
Chengfu Xu ◽  
Chao Lu ◽  
Huatuo Zhu ◽  
Chaohui Yu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Uric Acid ◽  
Hepatic Steatosis ◽  
Nlrp3 Inflammasome ◽  
Dependent Mechanism

scholarly journals Acute activation of NHE3 by dexamethasone correlates with activation of SGK1 and requires a functional glucocorticoid receptor

2007 ◽  
Vol 292 (1) ◽  
pp. C396-C404 ◽  
Author(s):  
Dongsheng Wang ◽  
Huanchun Zhang ◽  
Florian Lang ◽  
C. Chris Yun
Keyword(s):  
Glucocorticoid Receptor ◽  
Kinase Activity ◽  
Actinomycin D ◽  
Acute Effect ◽  
Protein Abundance ◽  
Transport Activity ◽  
Opossum Kidney ◽  
Opossum Kidney Cells ◽  
Dependent Mechanism ◽  
Stimulation Of

Glucocorticoids stimulate the intestinal absorption of Na+ and water partly by regulation of the Na+/H+ exchanger 3 (NHE3). Previous studies have shown both genomic and nongenomic regulation of NHE3 by glucocorticoids. Serum and glucocorticoid-inducible kinase 1 (SGK1) has been shown to be part of this cascade, where phosphorylation of NHE3 by SGK1 initiates the translocation of NHE3 to the cell surface. In the present work, we examined a series of changes in SGK1 and NHE3 induced by glucocorticoids using human colonic Caco-2 and opossum kidney cells. We found that dexamethasone rapidly stimulated SGK1 mRNAs, but a significant change in protein abundance was not detected. Instead, there was an increase in SGK1 kinase activity as early as at 2 h. An increase in NHE3 protein abundance was not detected until 12 h of dexamethasone exposure, although the transport activity was significantly stimulated at 4 h. These data demonstrate that the changes of SGK1 precede those of NHE3. Chronic regulation (24 h) of NHE3 was blocked completely by prevention of protein synthesis with cycloheximide or actinomycin D and by the glucocorticoid receptor blocker RU486. The acute effect of dexamethasone was similarly abrogated by RU486, but was insensitive to cycloheximide and actinomycin D. Similarly, the stimulation of SGK1 activity by dexamethasone was blocked by RU486 but not by actinomycin D. Together, these data show that the acute effect of glucocorticoids on NHE3 is mediated by a glucocorticoid receptor dependent mechanism that activates SGK1 in a nongenomic manner.

Sign in / Sign up

Export Citation Format

Share Document