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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.

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.

Much less research on regulation and function of selenoproteins has been conducted in domestic pigs than in rodents or humans, although pigs are an excellent model of human nutrition and medicine and pork is a widely consumed meat in the world. Phylogenetically, the 25 identified porcine selenoproteins fell into two primitive groups, and might be further divided into three parallel branches. Despite a high similarity to that of humans and rodents, the porcine selenoproteome exhibited the closest evolutionary relationship with that of sheep and cattle among eight domestic species. Expression (mRNA, protein, and/or enzyme activity) of 2/3 of the 25 porcine selenoproteins in various tissues of pigs was affected by dietary Se intakes, and 14 of them showed responses to a high fat diet. When dietary Se deficiency mainly down-regulated the expression of selected selenoproteins, dietary Se excess exerted rather diverse effects on their expression. Overdosing pigs with dietary Se induced hyperinsulinemia, along with lipid accumulation and protein increase, in the liver and muscle by affecting key genes and(or) proteins involved in the metabolisms of glucose, lipid, and protein. In conclusion, expression of porcine selenoproteins was highly responsive to dietary Se and fat intakes, and was involved in body glucose, lipid, and protein metabolism as those of rodents and humans.

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.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.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).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).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.

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). 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. Electronic supplementary material The online version of this article (10.1186/s12986-019-0332-0) contains supplementary material, which is available to authorized users.

BACKGROUND The involvement of cytochrome P450 (CYP450) isozymes and the selenogenome in selenium-mediated protection against aflatoxin B1 (AFB1)-induced adverse effects in broilers remains unclear. OBJECTIVE This study was designed first to determine whether selenium could reduce AFB1-induced hepatotoxic effects and then to determine whether these effects were due to changes in the CYP450 isozymes and selenogenome expression in the liver of chicks. METHODS Male avian broilers (aged 120 d) were allocated to 4 groups with 5 replicates of 6 birds to be included in a 2-by-2 factorial trial in which the main factors included supplementation of AFB1 (

The relationship between selenium (Se) and diabetes remains an evolving field. Early studies were focused on antioxidant benefits of Se in diabetic animals and patients. However, the discovery of type 2 diabetes-like phenotype in the glutathione peroxidase (GPX) 1 overexpression mice and the pro-diabetic potential of Se supplementation in cancer subjects have provoked both research and public interests on its role in diabetes. Limited human data indicate a Se baseline-dependent risk for diabetes associated with Se supplementations: potentiating the risk for diabetes only in subjects with high-Se status. Among the 25 selenoproteins, GPX1 exhibits dual roles in insulin synthesis, secretion, and signaling via regulation of redox homeostasis, and selenoprotein P has the counteraction effect on insulin signaling. Both GPX3 and selenoprotein S may play roles in diabetic etiology via mediating inflammation. Dysregulations of the two endoplasmic reticulum (ER)-resident selenoproteins, selenoproteins M and T, may disturb the redox homeostasis in ER, causing ER stress and increasing the diabetes risk. Iodothyronine deiodinases catalyze the metabolism of thyroid hormones and thus may affect the metabolism of glucose, lipids, and protein in the diabetic status. Polymorphism of selenoprotein genes in humans offers clues to the association of Se/selenoproteins and diabetes risk. In conclusion, effects of Se intake on the risk of diabetes are dose and baseline dependent. While underlying mechanisms for this paradox are partly understood through animal studies on the functions of several selenoproteins, appropriate Se intakes for the general public to prevent or treat diabetes warrant future research.

Background: Relations of the 25 mammalian selenoprotein genes with obesity and the associated inflammation remain unclear. Objective: This study explored impacts of high-fat diet-induced obesity on inflammation and expressions of selenoprotein and obesity-related genes in 10 tissues of pigs. Methods: Plasma and 10 tissues were collected from pigs (n = 10) fed a corn-soy–based control diet or that diet containing 3–7% lard from weanling to finishing (180 d). Plasma concentrations (n = 8) of cytokines and thyroid hormones and tissue mRNA abundance (n = 4) of 25 selenoprotein genes and 16 obesity-related genes were compared between the pigs fed the control and high-fat diets. Stepwise regression was applied to analyze correlations among all these measures, including the previously reported body physical and plasma biochemical variables. Results: The high-fat diet elevated (P < 0.05) plasma concentrations of tumor necrosis factor α, interleukin-6, leptin, and leptin receptor by 29–42% and affected (P < 0.05–0.1) tissue mRNA levels of the selenoprotein and obesity-related genes in 3 patterns. Specifically, the high-fat diet up-regulated 12 selenoprotein genes in 6 tissues, down-regulated 13 selenoprotein genes in 7 tissues, and exerted no effect on 5 genes in any tissue. Body weights and plasma triglyceride concentrations of pigs showed the strongest regressions to tissue mRNA abundances of selenoprotein and obesity-related genes. Among the selenoprotein genes, selenoprotein V and I were ranked as the strongest independent variables for the regression of phenotypic and plasma measures. Meanwhile, agouti signaling protein, adiponectin, and resistin genes represented the strongest independent variables of the obesity-related genes for the regression of tissue selenoprotein mRNA. Conclusions: The high-fat diet induced inflammation in pigs and affected their gene expression of selenoproteins associated with thioredoxin and oxidoreductase systems, local tissue thyroid hormone activity, endoplasmic reticulum protein degradation, and phosphorylation of lipids. This porcine model may be used to study interactive mechanisms between excess fat intake and selenoprotein function.

Background: Glutathione peroxidase (GPX) 4 and selenoprotein P (SELENOP) are abundant, and several variants are expressed in the testis.Objective: We determined the effects of dietary selenium deficiency or excess on sperm quality and expressions of GPX4 and SELENOP variants in rat testis and liver.Methods: After weaning, male Sprague-Dawley rats were fed a Se-deficient basal diet (BD) for 5 wk until they were 9 wk old [mean ± SEM body weight (BW) = 256 ± 5 g]. They were then fed the BD diet alone (deficient) or with 0.25 (adequate), 3 (excess), or 5 (excess) mg Se/kg for 4 wk. Testis, liver, blood, and semen were collected to assay for selenoprotein mRNA and protein abundances, selenium concentration, GPX activity, 8-hydroxy-deoxyguanosine concentration, and sperm quality.Results: Dietary selenium supplementations elevated (P < 0.05) tissue selenium concentrations and GPX activities. Compared with those fed BD + 0.25 mg Se/kg, rats fed BD showed lower (P < 0.05) BW gain (86%) and sperm density (57%) but higher (P < 0.05) plasma 8-hydroxy-deoxyguanosine concentrations (189%), and nonprogressive sperm motility (4.4-fold). Likewise, rats fed BD + 5 mg Se/kg had (P = 0.06) lower BW gain and higher (1.9-fold) sperm deformity rates than those in the selenium-adequate group. Compared with the selenium-adequate group, dietary selenium deficiency (BD) or excess (BD + 3 or 5 mg Se/kg) resulted in 45-77% lower (P < 0.05) nuclear Gpx4 (nGpx4) mRNA abundance in the testis. Rats fed BD had lower (P < 0.05) mRNA levels of 2 Selenop variants in both testis and liver than those in the other groups. Testicular SELENOP was 155-170% higher (P < 0.05) in rats fed BD + 5 mg Se/kg and hepatic c/mGPX4 was 13-15% lower (P < 0.05) in rats fed BD than in the other groups.Conclusions: The mRNA abundance of rat testicular nGPX4 responded to dietary selenium concentrations in similar ways to sperm parameters and may be used as a sensitive marker to assess appropriate Se status for male function.

Expression and function of selenoproteins in endocrine tissues remain unclear, largely due to limited sample availability. Pigs have a greater metabolic similarity and tissue size than rodents as a model of humans for that purpose. We conducted 2 experiments: 1) we cloned 5 novel porcine selenoprotein genes; and 2) we compared the effects of dietary selenium (Se) on mRNA levels of 12 selenoproteins, activities of 4 antioxidant enzymes, and Se concentrations in testis, thyroid, and pituitary with those in liver of pigs. In Experiment 1, porcine Gpx2, Sephs2, Sep15, Sepn1, and Sepp1 were cloned and demonstrated 84–94% of coding sequence homology to human genes. In Experiment 2, weanling male pigs (n = 30) were fed a Se-deficient (0.02 mg Se/kg) diet added with 0, 0.3, or 3.0 mg Se/kg as Se-enriched yeast for 8 wk. Although dietary Se resulted in dose-dependent increases (P < 0.05) in Se concentrations and GPX activities in all 4 tissues, it did not affect the mRNA levels of any selenoprotein gene in thyroid or pituitary. Testis mRNA levels of Txnrd1 and Sep15 were decreased (P < 0.05) by increasing dietary Se from 0.3 to 3.0 mg/kg. Comparatively, expressions of Gpx2, Gpx4, Dio3, and Sep15 were high in pituitary and Dio1, Sepp1, Sephs2, and Gpx1 were high in liver. In conclusion, the mRNA abundances of the 12 selenoprotein genes in thyroid and pituitary of young pigs were resistant to dietary Se deficiency or excess.

ObjectiveTo examine the vitamin D status, SNP of the vitamin D receptor gene (VDR) and the effects of vitamin D supplementation on parathyroid hormone and insulin secretion in adult males with obesity or normal weight in a subtropical Chinese city.DesignAn intervention trial.SettingShenzhen City, Guangdong Province, China.SubjectsFrom a cross-sectional survey conducted from June to July, eighty-two normal-weight and ninety-nine obese males (18–69 years) were screened to analyse their vitamin D status and for five SNP of VDR. From these individuals, in the same season of a different year, obese and normal-weight male volunteers (twenty-one per group) were included for an intervention trial with oral vitamin D supplementation at 1250 µg/week for 8 weeks.ResultsFor the survey, there was no significant difference (P>0·05) in baseline circulating 25-hydroxyvitamin D concentrations or in the percentages of participants in different categories of vitamin D status between the two groups. The VDR SNP, rs3782905, was significantly associated with obesity (P=0·043), but none of the examined SNP were correlated with serum 25-hydroxyvitamin D when adjusted for age, BMI and study group. After vitamin D supplementation, serum 25-hydroxyvitamin D concentration, hypersecretions of parathyroid hormone and insulin, and insulin resistance in the obese were changed beneficially (P<0·05); however, the increase in serum 25-hydroxyvitamin D was less than that of the normal-weight men.ConclusionsFor obese and normal-weight men of subtropical China, the summer baseline vitamin D status was similar. However, oral vitamin D supplementation revealed a decreased bioavailability of vitamin D in obese men and ameliorated their hypersecretion of parathyroid hormone and insulin resistance.

BACKGROUND Previous studies yielded controversial results about the alteration of lipid profiles in patients with subclinical hypothyroidism. We performed a meta-analysis to investigate the association between subclinical hypothyroidism and lipid profiles. MATERIAL AND METHODS We searched PubMed, Cochrane Library, and China National Knowledge Infrastructure articles published January 1990 through January 2014. Dissertation databases (PQDT and CDMD) were searched for additional unpublished articles. We included articles reporting the relationship between subclinical hypothyroidism and at least 1 parameter of lipid profiles, and calculated the overall weighted mean difference (WMD) with a random effects model. Meta-regression was used to explore the source of heterogeneity among studies, and the Egger test, Begg test, and the trim and fill method were used to assess potential publication bias. RESULTS Sixteen observational studies were included in our analysis. Meta-analysis suggested that the serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and total triglyceride levels were significantly increased in patients with subclinical hypothyroidism compared with euthyroidism individuals; the WMD were 12.17 mg/dl, 7.01 mg/dl, and 13.19 mg/dl, respectively (P

Although supranutrition of selenium (Se) is considered a promising anti-cancer strategy, recent human studies have shown an intriguing association between high body Se status and diabetic risk. This study was done to determine if a prolonged high intake of dietary Se actually induced gestational diabetes in rat dams and insulin resistance in their offspring. Forty-five 67-day-old female Wistar rats (n=15/diet) were fed a Se-deficient (0.01 mg/kg) corn–soy basal diet (BD) or BD+Se (as Se-yeast) at 0.3 or 3.0 mg/kg from 5 weeks before breeding to day 14 postpartum. Offspring (n=8/diet) of the 0.3 and 3.0 mg Se/kg dams were fed with the same respective diet until age 112 days. Compared with the 0.3 mg Se/kg diet, the 3.0 mg/kg diet induced hyperinsulinemia (P