N‐ϒ‐(l‐Glutamyl)‐l‐Selenomethionine Inhibits Fat Storage via the Stearoyl‐CoA Desaturases FAT‐6 and FAT‐7 and the Selenoprotein TRXR‐1 in Caenorhabditis elegans

Abstract

Scope Selenium is an important nutrient for human health. The influence of dietary selenium on lipid metabolism remains largely unknown. N‐γ‐(l‐glutamyl)‐l‐selenomethionine (Glu‐SeMet) on inhibition of fat accumulation and its underlying mechanisms in the nematode Caenorhabditis elegans are investigated. Methods and results Triacylglyceride quantification and post‐fixed Nile red staining methods are conducted to evaluate fat accumulation in wild‐type N2 worms in normal or high‐glucose diet. Glu‐SeMet (0.01 µm) treatment effectively reduces fat storage in wild‐type N2 C. elegans in both a normal and high‐glucose diet. Further evidence shows that Glu‐SeMet (0.01 µm) decreases the ratio of oleic acid/stearic acid (C18:1Δ9/C18:0) using gas chromatography–mass spectrometry analysis. The mRNA levels of fatty acid stearoyl‐CoA desaturases, FAT‐6 and FAT‐7, and the mediator‐15 (MDT‐15) are downregulated while the wild‐type N2 worms are co‐treated with high glucose and Glu‐SeMet (0.01 µm). The effect of reduced fat accumulation is absent in fat‐6, fat‐7, and trxr‐1 mutant worms under high glucose and Glu‐SeMet (0.01 µm) co‐treatment. Conclusions This study demonstrates that Glu‐SeMet inhibiting fat accumulation may be associated with FAT‐6 and FAT‐7 and the selenoprotein TRXR‐1 in C. elegans. This study implies a potential for Glu‐SeMet as a new treatment for obesity or its complications.

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity

“…Correspondingly, TXNRDs transcription in human SAT is significantly associated with lipogenesis and insulin resistance in adipocytes [99]. Moreover, antiadipogenic effect of N-γ-(l-glutamyl)-l-selenomethionine (Glu-SeMet) in glucose-exposed Caenorhabditis elegans was dependent on stearoyl-CoA desaturases (SCDs) and Txnrd1 [189]. The particular mechanisms linking TXNRD activity and adipogenesis may include modulation of adipocyte cell cycle.…”

Butein inhibits lipogenesis in Caenorhabditis elegans

“…The inhibition of only one SCD homolog ( fat‐7 ) by butein did not have any effects on fatty acids desaturation in C. elegans . Consistently, others have shown a reduced fatty acids desaturation occurs when both fat‐6 and fat‐7 are inhibited by bioactives 17,20,49,50 . The SCD inhibition by butein could be explained by its effects on transcription factors known to regulate lipogenesis, such as SREBPs and PPARs 20,30,31,50 .…”

“…Consistently, others have shown a reduced fatty acids desaturation occurs when both fat-6 and fat-7 are inhibited by bioactives. 17,20,49,50 The SCD inhibition by butein could be explained by its effects on transcription factors known to regulate lipogenesis, such as SREBPs and PPARs. 20,30,31,50 However, butein's effects on triglycerides reduction were independent of SBP-1 and NHR-49, and the butein's inhibitory effects on SCD homologs were not via SKN-1/Nrf pathway in C. elegans.…”

“…17,20,49,50 The SCD inhibition by butein could be explained by its effects on transcription factors known to regulate lipogenesis, such as SREBPs and PPARs. 20,30,31,50 However, butein's effects on triglycerides reduction were independent of SBP-1 and NHR-49, and the butein's inhibitory effects on SCD homologs were not via SKN-1/Nrf pathway in C. elegans. Therefore, whether butein inhibits directly SCD or via an upstream regulator needs further investigation.…”

Identification of γ-Glutamyl-Selenomethionine as the Principal Selenium Metabolite in a Selenium-Enriched Probiotic, Bifidobacterium longum, by Two-Dimensional HPLC-ICP MS and HPLC-ESI Orbitrap MS

“…Γ-Glu-Met was found to inhibit the growth of five human solid tumor cell lines and was related to insulin sensitivity in humans . Γ-Glu-SeMet also showed anti-obesity potential, via inhibiting fat storage, as well as anti-oxidant and anti-aging activities . In addition, our previous studies revealed that Se–B.…”