Selenium-binding protein 1 (SELENBP1) is a marker of mature adipocytes

Abstract

Selenium-binding protein 1 (SELENBP1) has recently been reported to catalyse the oxidation of methanethiol, an organosulfur compound produced by gut microbiota. Two of the reaction products of methanethiol oxidation, hydrogen peroxide and hydrogen sulphide, serve as signalling molecules for cell differentiation. Indeed, colonocyte differentiation has been found to be associated with SELENBP1 induction. Here, we show that SELENBP1 is induced when 3T3-L1 preadipocytes undergo terminal differentiation and maturation to adipocytes. SELENBP1 induction succeeded the up-regulation of known marker proteins of white adipocytes and the intracellular accumulation of lipids. Immunofluorescence microscopy revealed predominant cytoplasmic localisation of SELENBP1 in 3T3-L1 adipocytes, as demonstrated by co-staining with the key lipogenic enzyme, acetyl-CoA-carboxylase (ACC), located in cytosol. In differentiating 3T3-L1 cells, the mTOR inhibitor rapamycin and the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α) likewise suppressed SELENBP1 induction, adipocyte differentiation and lipid accumulation. However, lipid accumulation per se is not linked to SELENBP1 induction, as hepatic SELENBP1 was down-regulated in high fructose-fed mice despite increased lipogenesis in the liver and development of non-alcoholic fatty liver disease (NAFLD). In conclusion, SELENBP1 is a marker of cell differentiation/maturation rather than being linked to lipogenesis/lipid accumulation.

A Caenorhabditis elegans ortholog of human selenium-binding protein 1 is a pro-aging factor protecting against selenite toxicity

“…Subcellularly, Y37A1B.5:GFP is found predominantly in the cytoplasm (Fig. 3C), which is true also for human SELENBP1 [12]. Sporadically, in few worms only, GFP fluorescence is also detected in some anterior or posterior intestinal cells (Fig.…”

“…Neither the mode of selenite binding nor the physiological significance of SELENBP1 have been fully elucidated. Nevertheless, some associations with (patho-)physiological processes were described, including a link to cell differentiation [12,13] and a correlation between low SELENBP1 expression levels in tumor tissue and poor clinical outcome (for review, see Ref. [14]).…”

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity

“…Despite a relatively low Se content in adipose tissue [128,129] mapping of murine adipocyte proteome demonstrated high abundances of selenoproteins in gonadal white adipose tissue (WAT) [29]. Importance of Se for adipose tissue biology was also supported by the observation of the role of Se-binding protein 1 (SELENBP1) as a marker of mature adipocytes, being associated with lipid accumulation and other functional markers of adipocyte differentiation [141]. Peinado et al proposed that modulation of SELENBP1 expression in VAT may be associated with HIF-1 signaling in obesity [142].…”

A coupled enzyme assay for detection of selenium-binding protein 1 (SELENBP1) methanethiol oxidase (MTO) activity in mature enterocytes

“…SDS-PAGE and immunoblotting were performed as previously described [ 12 ], with minor modifications. Cell lysates or enriched proteins were run on SDS-polyacrylamide gels and electroblotted onto PVDF membranes (Carl Roth).…”

“…SELENBP1 is ubiquitously expressed, but its highest mRNA and protein levels were found in gastrointestinal tissues, liver and lung, as suggested by Pol et al [ 5 ] and data available through the Human Protein Atlas (version 20.0, https://www.proteinatlas.org/ENSG00000143416-SELENBP1/tissue ) [ 11 ]. Interestingly, SELENBP1 expression was described to be strongly induced in the course of cell differentiation not only in adipocytes [ 12 ] but also in intestinal epithelial cells [ 13 , 14 ], in the latter case resulting in an increase in SELENBP1 protein levels along the colonic crypt-luminal axis [ 13 ]. This would put cellular SELENBP1 in close proximity to the gut microbiome, the major (extracellular) source of its substrate, methanethiol.…”