Endoplasmic reticulum-resident selenoproteins and their roles in glucose and lipid metabolic disorders.

Glucose and lipid metabolic disorders (GLMDs), such as diabetes, dyslipidemia, metabolic syndrome, nonalcoholic fatty liver disease, and obesity, are significant public health issues that negatively impact human health. The endoplasmic reticulum (ER) plays a crucial role at the cellular level for lipid and sterol biosynthesis, intracellular calcium storage, and protein post-translational modifications. Imbalance and dysfunction of the ER can affect glucose and lipid metabolism. As an essential trace element, selenium contributes to various human physiological functions mainly through 25 types of selenoproteins (SELENOs). At least 10 SELENOs, with experimental and/or computational evidence, are predominantly found on the ER membrane or within its lumen. Two iodothyronine deiodinases (DIOs), DIO1 and DIO2, regulate the thyroid hormone deiodination in the thyroid and some external thyroid tissues, influencing glucose and lipid metabolism. Most of the other eight members maintain redox homeostasis in the ER. Especially, SELENOF, SELENOM, and SELENOS are involved in unfolded protein responses; SELENOI catalyzes phosphatidylethanolamine synthesis; SELENOK, SELENON, and SELENOT participate in calcium homeostasis regulation; and the biological significance of thioredoxin reductase 3 in the ER remains unexplored despite its established function in the thioredoxin system. This review examines recent research advances regarding ER SELENOs in GLMDs and aims to provide insights on ER-related pathology through SELENOs regulation.

Vitamin D3 exacerbates steatosis while calcipotriol inhibits inflammation in non-alcoholic fatty liver disease in Sod1 knockout mice: a comparative study of two forms of vitamin D.

The role of vitamin D (VD) in non-alcoholic fatty liver disease (NAFLD) remains controversial, possibly due to the differential effects of various forms of VD. In our study, Sod1 gene knockout (SKO) mice were utilized as lean NAFLD models, which were administered 15 000 IU VD3 per kg diet, or intraperitoneally injected with the active VD analog calcipotriol for 12 weeks. We found that VD3 exacerbated hepatic steatosis in SKO mice, with an increase in the levels of Cd36, Fatp2, Dgat2, and CEBPA. However, calcipotriol exerted no significant effect on hepatic steatosis. Calcipotriol inhibited the expression of Il-1a, Il-1b, Il-6, Adgre1, and TNF, with a reduction of NFκB phosphorylation in SKO mice. No effect was observed by either VD3 or calcipotriol on hepatocyte injury and hepatic fibrosis. Co-immunofluorescence stains of CD68, a liver macrophage marker, and VDR showed that calcipotriol reduced CD68 positive cells, and increased the colocalization of VDR with CD68. However, VD3 elevated hepatocyte VDR expression, with no substantial effect on the colocalization of VDR with CD68. Finally, we found that VD3 increased the levels of serum 25(OH)D3 and 24,25(OH)2D3, whereas calcipotriol decreased both. Both VD3 and calcipotriol did not disturb serum calcium and phosphate levels. In summary, our study found that VD3 accentuated hepatic steatosis, while calcipotriol diminished inflammation levels in SKO mice, and the difference might stem from their distinct cellular selectivity in activating VDR. This study provides a reference for the application of VD in the treatment of lean NAFLD.

Dissecting the role of cadmium, lead, arsenic, and mercury in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

The objective of the present study was to review the existing epidemiological and laboratory findings supporting the role of toxic metal exposure in non-alcoholic fatty liver disease (NAFLD). The existing epidemiological studies demonstrate that cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) exposure was associated both with an increased risk of NAFLD and altered biochemical markers of liver injury. Laboratory studies demonstrated that metal exposure induces hepatic lipid accumulation resulting from activation of lipogenesis and inhibition of fatty acid ß-oxidation due to up-regulation of sterol regulatory element-binding protein 1 (SREBP-1), carbohydrate response element binding protein (ChREBP), peroxisome proliferator-activated receptor γ (PPARγ), and down-regulation of PPARα. Other metabolic pathways involved in this effect may include activation of reactive oxygen species (ROS)/extracellular signal-regulated kinase (ERK) and inhibition of AMP-activated protein kinase (AMPK) signaling. The mechanisms of hepatocyte damage during development of metal-induced hepatic steatosis were shown to involve oxidative stress, endoplasmic reticulum stress, pyroptosis, ferroptosis, and dysregulation of autophagy. Induction of inflammatory response contributing to progression of NAFLD to non-alcoholic steatohepatitis (NASH) upon toxic metal exposure was shown to be mediated by up-regulation of nuclear factor κB (NF-κB) and activation of NRLP3 inflammasome. Moreover, epigenetic effects of the metals, as well as their effect on gut microbiota and gut wall integrity were also shown to mediate their role in NAFLD development. Despite being demonstrated for Cd, Pb, and As, the contribution of these mechanisms into Hg-induced NAFLD is yet to be estimated. Therefore, further studies are required to clarify the intimate mechanisms underlying the relationship between heavy metal and metalloid exposure and NAFLD/NASH to reveal the potential targets for treatment and prevention of metal-induced NAFLD.

The role of hypoxia-inducible factor 1 alpha (HIF-1α) modulation in heavy metal toxicity.

Hypoxia-inducible factor 1 (HIF-1) is an oxygen-sensing transcriptional regulator orchestrating a complex of adaptive cellular responses to hypoxia. Several studies have demonstrated that toxic metal exposure may also modulate HIF-1α signal transduction pathway, although the existing data are scarce. Therefore, the present review aims to summarize the existing data on the effects of toxic metals on HIF-1 signaling and the potential underlying mechanisms with a special focus on prooxidant effect of the metals. The particular effect of metals was shown to be dependent on cell type, varying from down- to up-regulation of HIF-1 pathway. Inhibition of HIF-1 signaling may contribute to impaired hypoxic tolerance and adaptation, thus promoting hypoxic damage in the cells. In contrast, its metal-induced activation may result in increased tolerance to hypoxia through increased angiogenesis, thus promoting tumor growth and contributing to carcinogenic effect of heavy metals. Up-regulation of HIF-1 signaling is mainly observed upon Cr, As, and Ni exposure, whereas Cd and Hg may both stimulate and inhibit HIF-1 pathway. The mechanisms underlying the influence of toxic metal exposure on HIF-1 signaling involve modulation of prolyl hydroxylases (PHD2) activity, as well as interference with other tightly related pathways including Nrf2, PI3K/Akt, NF-κB, and MAPK signaling. These effects are at least partially mediated by metal-induced ROS generation. Hypothetically, maintenance of adequate HIF-1 signaling upon toxic metal exposure through direct (PHD2 modulation) or indirect (antioxidant) mechanisms may provide an additional strategy for prevention of adverse effects of metal toxicity.

Biology and Roles in Diseases of Selenoprotein I Characterized by Ethanolamine Phosphotransferase Activity and Antioxidant Potential.

Selenoprotein I (SELENOI) has been demonstrated to be an ethanolamine phosphotransferase (EPT) characterized by a nonselenoenzymatic domain and to be involved in the main synthetic branch of phosphatidylethanolamine (PE) in the endoplasmic reticulum. Therefore, defects of SELENOI may affect the health status through the multiple functions of PE. On the other hand, selenium (Se) is covalently incorporated into SELENOI as selenocysteine (Sec) in its peptide, which forms a Sec-centered domain as in the other members of the selenoprotein family. Unlike other selenoproteins, Sec-containing SELENOI was formed at a later stage of animal evolution, and the high conservation of the structural domain for PE synthesis across a wide range of species suggests the importance of EPT activity in supporting the survival and evolution of organisms. A variety of factors, such as species characteristics (age and sex), diet and nutrition (dietary Se and fat intakes), SELENOI-specific properties (tissue distribution and rank in the selenoproteome), etc., synergistically regulate the expression of SELENOI in a tentatively unclear interaction. The N- and C-terminal domains confer 2 distinct biochemical functions to SELENOI, namely PE regulation and antioxidant potential, which may allow it to be involved in numerous physiological processes, including neurological diseases (especially hereditary spastic paraplegia), T cell activation, tumorigenesis, and adipocyte differentiation. In this review, we summarize advances in the biology and roles of SELENOI, shedding light on the precise regulation of SELENOI expression and PE homeostasis by dietary Se intake and pharmaceutical or transgenic approaches to modulate the corresponding pathological status.

A meta-analysis on the prevalence of Charcot-Marie-Tooth disease and related inherited peripheral neuropathies.

BACKGROUND: Charcot-Marie-Tooth disease and related inherited peripheral neuropathies (CMT&RIPNs) brings great suffering and heavy burden to patients, but its global prevalence rates have not been well described. METHODS: We searched major English and Chinese databases for studies reporting the prevalence of CMT&RIPNs from the establishment of the databases to September 26, 2022. Based on the age, gender, study design, study region, and disease subtype, the included studies were correspondingly synthesized for meta-analyses on the overall prevalence and/or the subgroup analyses by using pool arcsine transformed proportions in the random-effects model. RESULTS: Of the finally included 31 studies, 21 studied the whole age population and various types of CMT&RIPNs, and the others reported specific disease subtype(s) or adult or non-adult populations. The pooled prevalence was 17.69/100,000 (95% CI 12.32-24.33) for the whole age population and significantly higher for CMT1 [10.61/100,000 (95% CI 7.06-14.64)] than for other subtypes (P' < 0.001). Without statistical significance, the prevalence seemed higher in those aged ≥ 16 or 18 years (21.02/100,000) than in those aged < 16 years (16.13/100,000), in males (22.50/100,000) than in females (17.95/100,000), and in Northern Europe (30.97/100,000) than in other regions. CONCLUSION: CMT&RIPNs are relatively more prevalent as CMT1 in the disease subtypes, and probably prevalent in older ages, males, and Northern Europe. More studies on the epidemiological characteristics of CMT&RIPNs with well-defined diagnosis criteria are needed to improve the prevalence evaluation and to arouse more attention to health care support.

Gpx4, Selenov, and Txnrd3 Are Three Most Testis-Abundant Selenogenes Resistant to Dietary Selenium Concentrations and Actively Expressed During Reproductive Ages in Rats.

Almost all selenogenes are expressed in the testis, and those have the highest and constant expressions will be the primary candidates for functional analysis of selenium (Se) in male reproduction. This study aimed to profile the mRNA expressions of the testis-abundant selenogenes of rat models in responses to growth and dietary Se concentrations. Forty-eight weaning SD male rats were fed Se deficient basal diet (BD) for 5 weeks and then randomly grouped (n = 12/group) for being fed BD or BD plus 0.25, 3, or 5 mg Se/kg for 4 more weeks before sacrifice. Abundances of selenogenomic mRNAs in the liver and testis were determined with relative qPCR and those of the testis-abundant selenogenes in 13 kinds of tissues were assayed with a molecular beacon-based qPCR. Spatiotemporal expressions of rat selenogenome were also analyzed with the RNA-Seq transcriptomic data published by NCBI. mRNA abundances of glutathione peroxidase 4 (Gpx4), nuclear Gpx4 (nGpx4), selenoprotein V (Selenov), and thioredoxin reductase 3 (Txnrd3) in the testis were significantly higher than that in any other tissues (P < 0.05). Moreover, testicular mRNA abundances of Gpx4, Selenov, and Txnrd3 were not affected by levels of dietary Se supplementation (P > 0.05), and much higher at 6-21 weeks old than at 2 and 104 weeks old (P < 0.05). The result showed that Gpx4, Selenov, and Txnrd3 were most highly expressed in the testis of rats especially at reproductive ages and resistant to the impact of dietary Se levels, which suggested their specific importance in male reproduction.

Associations between Circulating SELENOP Level and Disorders of Glucose and Lipid Metabolism: A Meta-Analysis.

Selenoprotein P (SELENOP) is an extracellular antioxidant, selenium transporter, and hepatokine interfering with glucose and lipid metabolism. To study the association between the circulating SELENOP concentration and glucose and lipid metabolic diseases (GLMDs), including gestational diabetes (GD), metabolic syndrome (MetS), non-alcoholic fatty liver disease, obesity, and type 2 diabetes, as well as the individual markers, a meta-analysis was conducted by searching multiple databases from their establishment through March 2022 and including 27 articles published between October 2010 and May 2021, involving 4033 participants. Participants with GLMDs had higher levels of SELENOP than those without GLMDs (standardized mean difference = 0.84, 95% CI: 0.16 to 1.51), and the SELENOP levels were positively correlated with the markers of GLMDs (pooled effect size = 0.09, 95% CI: 0.02 to 0.15). Subgroup analyses showed that the SELENOP concentrations were higher in women with GD and lower in individuals with MetS than their counterparts, respectively. Moreover, SELENOP was positively correlated with low-density lipoprotein cholesterol, but not with the other markers of GLMDs. Thus, the heterogenicity derived from diseases or disease markers should be carefully considered while interpreting the overall positive association between SELENOP and GLMDs. Studies with a larger sample size and advanced design are warranted to confirm these findings.

Selenium-Enriched Cardamine violifolia Increases Selenium and Decreases Cholesterol Concentrations in Liver and Pectoral Muscle of Broilers.

BACKGROUND: Supernutrition of selenium (Se) in an effort to produce Se-enriched meat may inadvertently cause lipid accumulation. Se-enriched Cardamine violifolia (SeCv) contains >80% of Se in organic forms. OBJECTIVES: This study was to determine whether feeding chickens a high dose of SeCv could produce Se-biofortified muscle without altering their lipid metabolism. METHODS: Day-old male broilers were allocated to 4 groups (6 cages/group and 6 chicks/cage) and were fed either a corn-soy base diet (BD, 0.13-0.15 mg Se/kg), the BD plus 0.5 mg Se/kg as sodium selenite (SeNa) or as SeCv, or the BD plus a low-Se Cardamine violifolia (Cv, 0.20-0.21mg Se/kg). At week 6, concentrations of Se and lipid and expression of selenoprotein and lipid metabolism-related genes were determined in the pectoral muscle and liver. RESULTS: The 4 diets showed no effects on growth performance of broilers. Compared with the other 3 diets, SeCv elevated (P < 0.05) Se concentrations in the pectoral muscle and liver by 14.4-127% and decreased (P < 0.05) total cholesterol concentrations by 12.5-46.7% and/or triglyceride concentrations by 28.8-31.1% in the pectoral muscle and/or liver, respectively. Meanwhile, SeCv enhanced (P < 0.05) muscular α-linolenic acid (80.0%) and hepatic arachidonic acid (58.3%) concentrations compared with SeNa and BD, respectively. SeCv downregulated (P < 0.05) the cholesterol and triglyceride synthesis-related proteins (sterol regulatory element binding transcription factor 2 and diacylglycerol O-acyltransferase 2) and upregulated (P < 0.05) hydrolysis and ß-oxidation of fatty acid-related proteins (lipoprotein lipase, fatty acid binding protein 1, and carnitine palmitoyltransferase 1A), as well as selenoprotein P1 and thioredoxin reductase activity in the pectoral muscle and/or liver compared with SeNa. CONCLUSIONS: Compared with SeNa, SeCv effectively raised Se and reduced lipids in the liver and muscle of broilers. The effect was mediated through the regulation of the cholesterol and triglyceride biosynthesis and utilization-related genes.

Polymorphisms of the Vitamin D Receptor Gene and Sex-Differential Associations with Lipid Profiles in Chinese Han Adults.

OBJECTIVE: To explore the association of single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene ( VDR) with circulating lipids considering gender differences. METHODS: Of the Han Chinese adults recruited from a health examination center for inclusion in the study, the circulating lipids, 25-hydroxyvitamin D (25OHD), and other parameters were measured. The VDR SNPs of Cdx2 (rs11568820), Fok1 (rs2228570), Apa1 (rs7975232), and Taq1 (rs731236) were genotyped with a qPCR test using blood DNA samples, and their associations with lipids were analyzed using logistic regression. RESULTS: In the female participants ( n = 236 with dyslipidemia and 888 without dyslipidemia), multiple genotype models of Fok1 indicated a positive correlation of B (not A) alleles with LDLC level ( P < 0.05). In the male participants ( n = 299 with dyslipidemia and 564 without dyslipidemia), the recessive model of Cdx2 and the additive and recessive models of Fok1 differed ( P < 0.05) between the HDLC-classified subgroups, respectively, and Fok1 BB and Cdx2 TT presented interactions with 25OHD in the negative associations with HDLC ( P < 0.05). CONCLUSION: In the Chinese Han adults included in the study, the Fok1 B-allele of VDR was associated with higher LDLC in females, and the Fok1 B-allele and the Cdx2 T-allele of VDR were associated with lower HDLC in males. The interaction of VD and Fok1 BB or Cdx2 TT in males synergistically decreased HDLC levels.

Adipotropic effects of heavy metals and their potential role in obesity.

Epidemiological studies demonstrated an association between heavy metal exposure and the incidence of obesity and metabolic syndrome. However, the particular effects of metal toxicity on adipose tissue functioning are unclear. Therefore, recent findings of direct influence of heavy metals (mercury, cadmium, and lead) and metalloid (arsenic) on adipose tissue physiology are discussed while considering existing gaps and contradictions. Here, we provide a literature review addressing adipose tissue as a potential target of heavy metal toxicity. Experimental in vivo studies demonstrated a significant influence of mercury, cadmium, lead, and arsenic exposure on body adiposity. In turn, in vitro experiments revealed both up- and downregulation of adipogenesis associated with aberrant expression of key adipogenic pathways, namely CCAAT/enhancer-binding protein (C/EBP) and peroxisome proliferator-activated receptor gamma (PPARγ). Comparison of the existing studies on the basis of dose and route of exposure demonstrated that the effects of heavy metal exposure on adipose tissue may be dose-dependent, varying from increased adipogenesis at low-dose exposure to inhibition of adipose tissue differentiation at higher doses. However, direct dose-response data are available in a single study only for arsenic. Nonetheless, both types of these effects, irrespective of their directionality, contribute significantly to metabolic disturbances due to dysregulated adipogenesis. Particularly, inhibition of adipocyte differentiation is known to reduce lipid-storage capacity of adipose tissue, leading to ectopic lipid accumulation. In contrast, metal-associated stimulation of adipogenesis may result in increased adipose tissue accumulation and obesity. However, further studies are required to reveal the particular dose- and species-dependent effects of heavy metal exposure on adipogenesis and adipose tissue functioning.

Associations between metabolic syndrome and four heavy metals: A systematic review and meta-analysis.

Four most concerned heavy metal pollutants, arsenic, cadmium, lead, and mercury may share common mechanisms to induce metabolic syndrome (MetS). However, recent studies exploring the relationships between MetS and metal exposure presented inconsistent findings. We aimed to clarify the relationship between heavy metal exposure biomarkers and MetS using a meta-analysis and systematic review approach. Literature search was conducted in international and the Chinese national databases up to June 2020. Of selected studies, we extracted the relevant data and evaluated the quality of each study's methodology. We then calculated the pooled effect sizes (ESs), standardized mean differences (SMDs), and their 95% confidence intervals (CIs) using a random-effect meta-analysis approach followed by stratification analyses for control of potential confounders. Involving 55,536 participants, the included 22 articles covered 52 observational studies reporting ESs and/or metal concentrations on specific metal and gender. Our results show that participants with MetS had significantly higher levels of heavy metal exposure [pooled ES = 1.16, 95% CI: 1.09, 1.23; n = 42, heterogeneity I2 = 75.6%; and SMD = 0.22, 95% CI: 0.15, 0.29; n = 32, I2 = 94.2%] than those without MetS. Pooled ESs in the subgroups stratified by arsenic, cadmium, lead, and mercury were 1.04 (95% CI: 0.97, 1.10; n = 8, I2 = 61.0%), 1.10 (0.95, 1.27; 11, 45.0%), 1.21 (1.00, 1.48; 12, 82.9%), and 1.26 (1.06, 1.48; 11, 67.7%), respectively. Pooled ESs in the subgroups stratified by blood, urine, and the other specimen were 1.22 (95% CI: 1.08, 1.38; n = 26, I2 = 75.8%), 1.06 (1.00, 1.13; 14, 58.1%), and 2.41 (1.30, 4.43; 2, 0.0%), respectively. In conclusion, heavy metal exposure was positively associated with MetS. Further studies are warranted to examine the effects of individual metals and their interaction on the relationship between MetS and heavy metals.

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases.

Multiple medical, lifestyle, and environmental conditions, including smoking and particulate pollution, have been considered as risk factors for COronaVIrus Disease 2019 (COVID-19) susceptibility and severity. Taking into account the high level of toxic metals in both particulate matter (PM2.5) and tobacco smoke, the objective of this review is to discuss recent data on the role of heavy metal exposure in development of respiratory dysfunction, immunotoxicity, and severity of viral diseases in epidemiological and experimental studies, as to demonstrate the potential crossroads between heavy metal exposure and COVID-19 severity risk. The existing data demonstrate that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and respiratory diseases (COPD, bronchitis). These observations corroborate laboratory findings on the role of heavy metal exposure in impaired mucociliary clearance, reduced barrier function, airway inflammation, oxidative stress, and apoptosis. The association between heavy metal exposure and severity of viral diseases, including influenza and respiratory syncytial virus has been also demonstrated. The latter may be considered a consequence of adverse effects of metal exposure on adaptive immunity. Therefore, reduction of toxic metal exposure may be considered as a potential tool for reducing susceptibility and severity of viral diseases affecting the respiratory system, including COVID-19.

Genetic polymorphisms of superoxide dismutase 1 are associated with the serum lipid profiles of Han Chinese adults in a sexually dimorphic manner.

Inspired by the mechanistic correlations between superoxide dismutase 1 (SOD1) and lipid metabolism, the associations of SOD1 single nucleotide polymorphisms (SNPs) with circulating lipid levels were explored. In 2621 Chinese Han adults, randomly recruited from a health examination center without organic diseases, cancers, and pregnancy, three tag SNPs, rs4998557, rs1041740, and rs17880487 selected by Haploview software were genotyped with a probe-based real-time quantitative PCR method. In both genders, most parameters of the dyslipidemia adults were inferior (P < 0.001) to those of the non-dyslipidemia adults, and genotype frequencies of rs4998557 and rs17880487 were significantly different (P < 0.05) between the normal and abnormal subgroups of total cholesterol (TC) or high-density lipoprotein cholesterol (HDLC). Adjusted for confounding factors, logistic regression analyses revealed that in males rs4998557A, rs1041740T, and rs17880487T reduced the risk of high TC and/or LDLC (P < 0.05), and rs4998557A and rs17880487T increased the risk of low HDLC (P < 0.05); but in females, none of the SNPs had associations with any of the lipid parameters (P > 0.05). Conclusively, characterized by a sexual dimorphism, the SOD1 polymorphisms were associated with the lipid disorders in the adult males but not females of the Chinese Han population.

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity.

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.

High serum concentration of selenium, but not calcium, cobalt, copper, iron, and magnesium, increased the risk of both hyperglycemia and dyslipidemia in adults: A health examination center based cross-sectional study.

BACKGROUND: Metabolic disorders of glucose and lipid were associated with some mineral elements, and data were warranted from various contexts to make the association more explicit. OBJECTIVE: To investigate the relationships between the serum concentrations of six mineral elements (calcium, cobalt, copper, iron, magnesium, and selenium) and the risk of hyperglycemia and dyslipidemia in adults. METHODS: The basic information and the over-night fasting serum samples of adults were randomly collected at a health examination center. The serum concentrations of glucose and lipids were measured with an automatic biochemical analyzer, and the mineral elements were measured with an inductively coupled plasma mass spectrometer. Data were analyzed between the hyperglycemia group (HGg) and the normal glucose group (NGg) as well as between the dyslipidemia group (DLg) and the normal lipid group (NLg). RESULTS: A total of 1466 adults aged 22-81 years (male/female = 1.8) were included, 110 in the HGg and 1356 in the NGg, or 873 in the DLg and 593 in the NLg. The serum element concentration medians [P50 (P25-P75)] significantly different between the HGg and the NGg were 0.83 (0.75-0.94) vs. 0.76 (0.68-0.87) mg/L for copper and 100 (90-110) vs. 94 (87-103) µg/L for selenium (P < 0.001), while those between the DLg and the NLg were 99 (92-110) vs. 97 (90-106) mg/L for calcium, 0.78 (0.69-0.88) vs. 0.75 (0.66-0.85) mg/L for copper, 1.7 (1.4-2.0) vs. 1.6 (1.3-2.0) mg/L for iron, 24 (22-28) vs. 23 (22-27) mg/L for magnesium, and 97 (89-106) vs. 92 (84-100) µg/L for selenium (P < 0.05). When the copper and selenium between the HGg and the NGg were analyzed by logistic regression with age, gender, body mass index, and mineral elements adjusted, only the highest quartile of selenium concentration had association with the increased risk of hyperglycemia [quartile (Q) 4 against Q1: OR = 2.9, 95 % CI = 1.5-5.5, P < 0.001). When the five differed mineral elements between the DLg and the NLg were similarly analyzed, only iron and selenium had associations with the increased risk of dyslipidemia (e.g., Q4 against Q1: OR = 1.4, 95 % CI = 1.1-2.0 for iron and OR = 2.9, 95 % CI = 2.1-4.0 for selenium, P < 0.05). CONCLUSION: In contrast to those of calcium, cobalt, copper, iron, and magnesium, the higher serum concentration of selenium increased the risk of both hyperglycemia and dyslipidemia in the study population of adult Chinese.

The GC2 haplotype of the vitamin D binding protein is a risk factor for a low plasma 25-hydroxyvitamin D concentration in a Han Chinese population.

BACKGROUND: The GC haplotype of the vitamin D binding protein (encoded by the GC gene) might be a risk factor to the vitamin D (VD) nutritional status for many populations, while evidences from the Chinese Han population are sparse. We test the association between vitamin D binding protein genotypes and VD status as well as the metabolic parameters of glucose and lipids in a Han Chinese population. METHODS: In a cross-sectional study conducted at a health examination centre (registered in ClinicalTrials.gov as QLS2013), 2641 adults were included and grouped according to their plasma 25-hydroxyvitamin D (25OHD) concentrations as VD deficient (VDD), insufficient (VDI), or sufficient (VDS). The rs7041 and rs4588 genotypes were analysed with a molecular beacon-based qPCR method using blood samples. RESULTS: Plasma 25OHD concentrations were lower in the GC2/2, rs7041T/T, and rs4588A/A genotypes than the GC1f/1s, rs7041G/T, and rs4588C/C genotypes (P <  0.05). After adjusting for confounders, the GC2 haplotype increased the risk of low VD status (P <  0.05) in both genders. More genotypic models revealed the negative contributions of rs4588A than rs7041T to low VD status (P <  0.05). The combined rates of VDD and VDI were 80.2% in males and 86.1% in females. Compared with VDI, VDS, or both, VDD showed higher plasma concentrations of fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides in males (P <  0.05); however, no significant differences were found with regard to these parameters between the subgroups defined by the GC genotypes (P > 0.05). CONCLUSIONS: In a Han Chinese population, the GC2 haplotype or more exactly rs4588A is a risk factor for low VD status but is not associated with glucose and lipid metabolic disorders, which are inversely correlated with the circulating 25OHD concentration in males. TRIAL REGISTRATION: The study was retrospectively registered in January 2018 as NCT03406234 in the ClinicalTrials.gov online system.

Role of glutathione peroxidase 1 in glucose and lipid metabolism-related diseases.

Glutathione peroxidase 1 (GPX1) is a selenium-dependent enzyme that reduces intracellular hydrogen peroxide and lipid peroxides. While past research explored regulations of gene expression and biochemical function of this selenoperoxidase, GPX1 has recently been implicated in the onset and development of chronic diseases. Clinical data have shown associations of human GPX1 gene variants with elevated risks of diabetes. Knockout and overexpression of Gpx1 in mice may induce types 1 and 2 diabetes-like phenotypes, respectively. This review assembles the latest advances in this new field of selenium biology, and attempts to postulate signal and molecular mechanisms mediating the role of GPX1 in glucose and lipid metabolism-related diseases. Potential therapies by harnessing the beneficial effects of this ubiquitous redox-modulating enzyme are briefly discussed.