scholarly journals Sex Hormone Binding Globulin (SHBG) Mitigates ER Stress in Hepatocytes In Vitro and Ex Vivo

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 755
Author(s):  
Katarzyna Kornicka-Garbowska ◽  
Lynda Bourebaba ◽  
Michael Röcken ◽  
Krzysztof Marycz
Keyword(s):  
Metabolic Syndrome ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Large Animal Model ◽  
Large Animal ◽  
Hormone Binding

Despite multiple research studies regarding metabolic syndrome and diabetes, the full picture of their molecular background and pathogenies remains elusive. The latest studies revealed that sex hormone-binding globulin (SHBG)—a serum protein released mainly by the liver—may participate in metabolic dysregulation, as its low serum level correlates with a risk for obesity, metabolic syndrome, and diabetes. Yet, the molecular phenomenon linking SHBG with these disorders remains unclear. In the presented study, we investigate how exogenous SHBG affects metabolically impaired hepatocytes with special attention to endoplasmic reticulum stress (ER stress) and lipid metabolism both in vitro and ex vivo. For that reason, palmitate-treated HepG2 cells and liver tissue samples collected post mortem were cultured in the presence of 50 nM and 100 nM SHBG. We found that SHBG protects against ER stress development and its progression. We have found that SHBG decreased the expression levels of inositol-requiring enzyme 1 (IRE1α), activating transcription factor 6 (ATF6), DNA damage-inducible transcript 3 (CHOP), and immunoglobulin heavy chain-binding protein (BIP). Furthermore, we have shown that it regulates lipolytic gene expression ex vivo. Additionally, herein, we deliver a novel large-animal model to study SHBG in translational research. Our data provide new insights into the cellular and molecular mechanisms by which SHBG modulates hepatocyte metabolism and offer a new experimental approach to study SHBG in human diseases.

scholarly journals Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Hiroki Yamazaki ◽  
Akifumi Kushiyama ◽  
Hideyuki Sakoda ◽  
Midori Fujishiro ◽  
Takeshi Yamamotoya ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Protective Effect ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Lipid Degradation ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
20 Nm

Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for metabolic syndrome including diabetes, obesity, and cardiovascular events. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains unknown. In this study, using adipocytes and macrophages, we focused on the in vitro effects of SHBG on inflammation as well as lipid metabolism. Incubation with 20 nM SHBG markedly suppressed lipopolysaccharide- (LPS-) induced inflammatory cytokines, such as MCP-1, TNFα, and IL-6 in adipocytes and macrophages, along with phosphorylations of JNK and ERK. Anti-inflammatory effects were also observed in 3T3-L1 adipocytes cocultured with LPS-stimulated macrophages. In addition, SHBG treatment for 18 hrs or longer significantly induced the lipid degradation of differentiated 3T3-L1 cells, with alterations in its corresponding gene and protein levels. Notably, these effects of SHBG were not altered by coaddition of large amounts of testosterone or estradiol. In conclusion, SHBG suppresses inflammation and lipid accumulation in macrophages and adipocytes, which might be among the mechanisms underlying the protective effect of SHBG, that is, its actions which reduce the incidence of metabolic syndrome.

scholarly journals The relationship between components of metabolic syndrome and plasma level of sex hormone-binding globulin

2019 ◽  
Vol 29 (2) ◽  
Author(s):  
Amin Alinezhad ◽  
Fatemeh Jafari
Keyword(s):  
Metabolic Syndrome ◽  
Plasma Level ◽  
Lipid Profiles ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Metabolic Abnormalities ◽  
Hormone Binding ◽  
Men And Women ◽  
Shbg Level ◽  
The Relationship

Plasma concentration of sex hormone-binding globulin (SHBG), as an androgen binding protein, is impressed by many physiological and environmental factors. Recent studies have shown that plasma level of SHBG is related to some components of metabolic syndrome (MetS); however, in contrast, few articles failed to show any associations between SHBG and MetS. So, this study was conducted to investigate the relationship between Components of Metabolic Syndrome and Plasma Level of Sex Hormone-Binding Globulin. In this study, after measuring the plasma level of SHBG in 84 individuals, the relation between MetS and the plasma level of SHBG was investigated. After evaluating the plasma level of SHBG and metabolic abnormalities in men and women, we investigated the factors which mentioned above in two groups including patients with and without MetS. Also, the metabolic abnormalities which evaluated in this study including plasma level of 25-hydroxyvitamin D, serum uric acid (SUA), Albumin, lipid profiles and etc. according to five components of MetS. Our result shows that SHBG could contributed to some laboratory parameters such as LDL-C (P<0.05), total cholesterol (P<0.05), triglycerides (P<0.05) and etc. in men, but not in women. On the other hand, we observed that concentration of SHBG is higher in patients with MetS (P<0.05); however, results from our experiment showed that there is no relation between lower level of SHBG and five components of MetS such as central obesity, raised fasting plasma glucose (FPG) (P>0.05), reduced HDL-C (P>0.05), raised triglycerides (P>0.05) and raised blood pressure (P>0.05) in both men and women. There is a significant association between SHBG and Log-Hip Circumference (P<0.05), Non-HDL-C (P<0.05) and Log-25(OH)D (P<0.05) was seen in this cross-section study in both men and women. Results obtained from our study suggest that SHBG is not a powerful enough factor to use as a predictor of MetS alone and there is no association between plasma level of SHBG and development of five components of MetS, however, lower SHBG level may contributed to lipid profiles.

scholarly journals Light-degradable hydrogels as dynamic triggers for gastrointestinal applications

2020 ◽  
Vol 6 (3) ◽  
pp. eaay0065 ◽  
Author(s):  
Ritu Raman ◽  
Tiffany Hua ◽  
Declan Gwynne ◽  
Joy Collins ◽  
Siddartha Tamang ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Implantable Devices ◽  
Large Animal Model ◽  
Large Animal ◽  
Gi Tract ◽  
Biomedical Device ◽  
Precise Tool ◽  
And Performance

Triggerable materials capable of being degraded by selective stimuli stand to transform our capacity to precisely control biomedical device activity and performance while reducing the need for invasive interventions. Here, we describe the development of a modular and tunable light-triggerable hydrogel system capable of interfacing with implantable devices. We apply these materials to two applications in the gastrointestinal (GI) tract: a bariatric balloon and an esophageal stent. We demonstrate biocompatibility and on-demand triggering of the material in vitro, ex vivo, and in vivo. Moreover, we characterize performance of the system in a porcine large animal model with an accompanying ingestible LED. Light-triggerable hydrogels have the potential to be applied broadly throughout the GI tract and other anatomic areas. By demonstrating the first use of light-degradable hydrogels in vivo, we provide biomedical engineers and clinicians with a previously unavailable, safe, dynamically deliverable, and precise tool to design dynamically actuated implantable devices.

scholarly journals Human sex hormone-binding globulin does not provide metabolic protection against diet-induced obesity and dysglycemia in mice

2018 ◽  
Vol 7 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Yael Sofer ◽  
Nava Nevo ◽  
Michal Vechoropoulos ◽  
Gabi Shefer ◽  
Etty Osher ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fasting Blood Glucose ◽  
Serum Triglyceride ◽  
Tolerance Test ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Wild Type ◽  
Diet Induced Obesity ◽  
Increased Risk

Background Sex hormone-binding globulin (SHBG) is the main transporter of sex hormones in most vertebrates. Low SHBG levels have been linked to increased risk for diabetes and metabolic syndrome. Polymorphisms of the SHBG gene linked to low SHBG protein levels also strongly predicted increased risk of type 2 diabetes, thus raising the possibility that SHBG may play a role in the pathogenesis of insulin resistance and diabetes. Aim To examine whether expression of human SHBG in mice may ameliorate the development of diabetes and metabolic syndrome in response to a high-fat diet (HFD). Methods Transgene mice expressing a human SHBG transgene (SHBG+) (N = 10/11; males/females) and their wild type littermates (N = 12/8; males/females) were fed HFD for 4.5 months. Results HFD induced comparable obesity in control and SHBG+ mice. Male transgenes had higher muscle mass after 2–3.5 months HFD (0.43 ± 0.028 (n = 4) vs 0.38 ± 0.053 g (n = 7), P = 0.05). Fasting blood glucose, as well as insulin or HOMA-IR, was not different in transgenic vs wild-type males after 4–5 months HFD. Female transgenes had higher fasting glucose (152 ± 29 (n = 7) vs 115 ± 27 mg/dL, P = 0.01 (n = 8)), but mean insulin and HOMA-IR were not different. Likewise, insulin tolerance test and intra-peritoneal glucose tolerance test (GTT) were not different. Finally, SHBG+ mice were not different from controls in terms of liver enzymes, serum triglyceride levels and blood pressure. Conclusion In mice with diet-induced obesity, human SHBG did not protect against development of obesity or dysglycemia.

Influence of sex hormone binding globulin and serum albumin on the conversion of androstenedione to testosterone by human erythrocytes

1981 ◽  
Vol 96 (1) ◽  
pp. 136-140 ◽  
Author(s):  
M. Egloff ◽  
N. Savouré ◽  
J. Tardivel-Lacombe ◽  
C. Massart ◽  
M. Nicol ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Binding Sites ◽  
Sex Hormone ◽  
Human Erythrocytes ◽  
Sex Hormone Binding Globulin ◽  
Total Plasma ◽  
Hormone Binding ◽  
High Binding Affinity

Abstract. The influence of human serum albumin and sex hormone binding globulin (SHBG) on the enzymic conversion of androstenedione to testosterone in human erythrocytes was investigated in vitro. Total plasma and albumin delayed the conversion rate of androstenedione, while SHBG increased it markedly. The effect of SHBG was largely abolished by heating to 60°C for 1 h and by saturating its binding sites by DHT. The effect of both proteins was found to be related to their concentration. It appears that the binding sites of albumin provide a mechanism for retarding androstenedione uptake by the erythrocytes and that the high binding affinity of SHBG for testosterone facilitates the diffusion of this steroid out of the cell and thus, displaces the chemical equilibrium within the cell.

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