Selenoprotein M Promotes Hypothalamic Leptin Signaling and Thioredoxin Antioxidant Activity

Gong, Ting; Hashimoto, Ann C.; Sasuclark, Alexandru R.; Khadka, Vedbar S.; Gurary, Alexandra; Pitts, Michael R.

doi:10.1089/ars.2018.7594

Cited by 37 publications

(36 citation statements)

References 46 publications

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“…A large number of genes have been revealed in the hypothalamic tissue which is affected by Sel M deficiency, including a protein interacting with thioredoxin, a negative regulator of the TXN system. In general, these data confirm that Sel M is a positive regulator of leptin signaling and TXN antioxidant activity in the hypothalamus (Gong et al, 2019) Using a Hek293 cell model, it was found that overexpression of HSF1 (heat shock factor) and activation of heat shock increases promoter activity and levels of mRNA and SELENOF protein (Selenoprotein F) as well as sodium selenite treatment. This can be regarded as the fact that overexpression and knockdown of HSF1 show the influence of HSF1gene transcription regulation on SELENOF and revealed the molecular mechanism of regulation of the SELENOF gene by the HSF1 participation in selenotranscriptome (Ren еt al., 2019).…”

Section: Fig 4 Regulation Of Sel K Incorporation Through By Vcp Ansupporting

confidence: 65%

FN1 mRNA expression of fibronectin 1 and distribution of fibronectin-associated leukocytes in humans with chronic diffuse liver diseases

Dolhikh

Maslak

Chernenko

et al. 2020

Regul. Mech. Biosyst.

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Chronic diffuse liver diseases are characterized by continuous progression of fibrosis, ultimately leading to cirrhosis with the following loss of the normal functioning of this organ due to excessive accumulation of the components of extracellular matrix. To find new, more available diagnostic markers of detecting disorders in the liver, we used methods of antifungal cytofluorometry and quantitative real-time polymerase chain reaction. Intensity of exposure of fibronectin and plasmatic membrane of lymphocytes in the group of patients with chronic diffuse diseases compared with the control group of practically healthy donors decreased both inside and on the surface of the cells respectively by 45.3% and 16.2%. Similar tendency towards decrease was observed during the assays of the level of the exposure of fibronectin on the surface and inside the blood granulocytes: by 25.0% and 36.5%, respectively. In the blood of the patients suffering from chronic diffuse diseases, compared with the control group, there was determined reliable increase in percentage of lymphocytes and granulocytes which contain topical fibronectin, by 32.3% and 2.78 times, correspondingly. The level of monocytes (as a percentage) with cell-associated fibronectin and fibronectin localized inside, by contrast, reliably decreased in 2.07 and 4.50 times, respectively. Analysis of the expression of FN1 in lymphocytes of blood of the studied groups using quantitative real-time polymerase chain reaction revealed decrease in the level of FN1 mRNA expression by 34.0% in the group of ill patients compared with the control group. We determined excellent diagnostic informativeness of the parameters of the level of exposure of fibronectin inside and on the surface of granulocytes and prognostic accuracy of the classifier from these parameters at the level of 100% using the method of support vector machine, SVM. High levels of diagnostic informativeness were recorded for the tests of all types of analyzed leukocytes with cell-associated fibronectin, and the classifiers based on the pair combinations of the tests with cell-associated fibronectin and fibronectin localized within the cells provide high diagnostic accuracy of the prognosis. Because the mentioned indicators are highly-sensitive tests, they can be proposed for early diagnostics and evaluation of the effectiveness of the conducted therapy of chronic diffuse liver diseases, which would allow reducing the use of paracentetic trepanobiopsy, a painful and risky procedure, which still remains the main type of diagnostic.

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Section: Fig 4 Regulation Of Sel K Incorporation Through By Vcp Ansupporting

confidence: 65%

FN1 mRNA expression of fibronectin 1 and distribution of fibronectin-associated leukocytes in humans with chronic diffuse liver diseases

Dolhikh

Maslak

Chernenko

et al. 2020

Regul. Mech. Biosyst.

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“…This suggestion is supported by the observation of high rate of selenoprotein transcription in Agouti related protein (Agrp) and Proopiomelanocortin (POMC)-expressing neurons [245]. Tight interrelationship between leptin signaling and Selenom was demonstrated by Gong et al (2019). Particularly, leptin increased hypothalamic Selenom expression, whereas Selenom deficiency significantly impaired leptin-induced STAT3 phosphorylation and subsequent cytosolic calcium responses [246].…”

Section: Se In Central Control Of Food Intakementioning

confidence: 95%

“…Tight interrelationship between leptin signaling and Selenom was demonstrated by Gong et al (2019). Particularly, leptin increased hypothalamic Selenom expression, whereas Selenom deficiency significantly impaired leptin-induced STAT3 phosphorylation and subsequent cytosolic calcium responses [246]. Selenocysteine-tRNA gene (Trsp)-KO using rat-insulin-promoter-driven-Cre (RIP-Cre) in mice resulted in a significant suppression of leptin signaling and reduction of POMC-positive neurons in hypothalamus, whereas Nrf2 signaling reversed both hypothalamic oxidative stress and leptin resistance [247].…”

Section: Se In Central Control Of Food Intakementioning

confidence: 99%

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity

et al. 2020

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Selenium (Se) homeostasis is tightly related to carbohydrate and lipid metabolism, but its possible roles in obesity development and in adipocyte metabolism are unclear. The objective of the present study is to review the current data on Se status in obesity and to discuss the interference between Se and selenoprotein metabolism in adipocyte physiology and obesity pathogenesis. The overview and meta-analysis of the studies on blood Se and selenoprotein P (SELENOP) levels, as well as glutathione peroxidase (GPX) activity in obese subjects, have yielded heterogenous and even conflicting results. Laboratory studies demonstrate that Se may modulate preadipocyte proliferation and adipogenic differentiation, and also interfere with insulin signaling, and regulate lipolysis. Knockout models have demonstrated that the selenoprotein machinery, including endoplasmic reticulum-resident selenoproteins together with GPXs and thioredoxin reductases (TXNRDs), are tightly related to adipocyte development and functioning. In conclusion, Se and selenoproteins appear to play an essential role in adipose tissue physiology, although human data are inconsistent. Taken together, these findings do not support the utility of Se supplementation to prevent or alleviate obesity in humans. Further human and laboratory studies are required to elucidate associations between Se metabolism and obesity.

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“…Schriever et al found that conditional KO of the selenoprotein glutathione peroxidase 4 (GPx4) in agouti-related peptide (Agrp)-positive neurons in the hypothalamus exacerbates diet-induced obesity [18]. Additionally, selenoprotein M (SelM) was found to support hypothalamic leptin signaling [19], which may underlie the obesity phenotype observed in SelM KO mice [7]. Circulating leptin acts upon neurons in the hypothalamus, including inhibiting Agrp neurons, to promote a negative energy balance.…”

Section: Introductionmentioning

confidence: 99%

Agrp-Specific Ablation of Scly Protects against Diet-Induced Obesity and Leptin Resistance

et al. 2019

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Selenium, an essential trace element known mainly for its antioxidant properties, is critical for proper brain function and regulation of energy metabolism. Whole-body knockout of the selenium recycling enzyme, selenocysteine lyase (Scly), increases susceptibility to metabolic syndrome and diet-induced obesity in mice. Scly knockout mice also have decreased selenoprotein expression levels in the hypothalamus, a key regulator of energy homeostasis. This study investigated the role of selenium in whole-body metabolism regulation using a mouse model with hypothalamic knockout of Scly. Agouti-related peptide (Agrp) promoter-driven Scly knockout resulted in reduced weight gain and adiposity while on a high-fat diet (HFD). Scly-Agrp knockout mice had reduced Agrp expression in the hypothalamus, as measured by Western blot and immunohistochemistry (IHC). IHC also revealed that while control mice developed HFD-induced leptin resistance in the arcuate nucleus, Scly-Agrp knockout mice maintained leptin sensitivity. Brown adipose tissue from Scly-Agrp knockout mice had reduced lipid deposition and increased expression of the thermogenic marker uncoupled protein-1. This study sheds light on the important role of selenium utilization in energy homeostasis, provides new information on the interplay between the central nervous system and whole-body metabolism, and may help identify key targets of interest for therapeutic treatment of metabolic disorders.

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Selenoprotein M Promotes Hypothalamic Leptin Signaling and Thioredoxin Antioxidant Activity

Cited by 37 publications

References 46 publications

FN1 mRNA expression of fibronectin 1 and distribution of fibronectin-associated leukocytes in humans with chronic diffuse liver diseases

FN1 mRNA expression of fibronectin 1 and distribution of fibronectin-associated leukocytes in humans with chronic diffuse liver diseases

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity

Agrp-Specific Ablation of Scly Protects against Diet-Induced Obesity and Leptin Resistance

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