Maternal seafood consumption is associated with improved selenium status: Implications for child health.

Selenium (Se) is required for synthesis of selenocysteine (Sec), an amino acid expressed in the active sites of Se-dependent enzymes (selenoenzymes), including forms with essential functions in fetal development, brain activities, thyroid hormone metabolism, calcium regulation, and to prevent or reverse oxidative damage. Homeostatic mechanisms normally ensure the brain is preferentially supplied with Se to maintain selenoenzymes, but high methylmercury (CH3Hg) exposures irreversibly inhibit their activities and impair Sec synthesis. Due to Hg's high affinity for sulfur, CH3Hg initially binds with the cysteine (Cys) moieties of thiomolecules which are selenoenzyme substrates. These CH3Hg-Cys adducts enter selenoenzyme active sites and transfer CH3Hg to Sec, thus irreversibly inhibiting their activities. High CH3Hg exposures are uniquely able to induce a conditioned Se-deficiency that impairs synthesis of brain selenoenzymes. Since the fetal brain lacks Se reserves, it is far more vulnerable to CH3Hg exposures than adult brains. This prompted concerns that maternal exposures to CH3Hg present in seafood might impair child neurodevelopment. However, typical varieties of ocean fish contain far more Se than CH3Hg. Therefore, eating them should augment Se-status and thus prevent Hg-dependent loss of fetal selenoenzyme activities. To assess this hypothesis, umbilical cord blood and placental tissue samples were collected following delivery of a cohort of 100 babies born on Oahu, Hawaii. Dietary food frequency surveys of the mother's last month of pregnancy identified groups with no (0 g/wk), low (0-12 g/wk), or high (12 + g/wk) levels of ocean fish consumption. Maternal seafood consumption increased Hg contents in fetal tissues and resulted in ∼34% of cord blood samples exceeding the EPA Hg reference level of 5.8 ppb (0.029 µM). However, Se concentrations in these tissues were orders of magnitude higher and ocean fish consumption caused cord blood Se to increase ∼9.4 times faster than Hg. Therefore, this study supports the hypothesis that maternal consumption of typical varieties of ocean fish provides substantial amounts of Se that protect against Hg-dependent losses in Se bioavailability. Recognizing the pivotal nature of the Hg:Se relationship provides a consilient perspective of seafood benefits vs. risks and clarifies the reasons for the contrasting findings of certain early studies.

Regulation of thyroid hormones and branchial iodothyronine deiodinases during freshwater acclimation in tilapia.

Euryhaline fishes are capable of maintaining osmotic homeostasis in a wide range of environmental salinities. Several pleiotropic hormones, including prolactin, growth hormone, and thyroid hormones (THs) are mediators of salinity acclimation. It is unclear, however, the extent to which THs and the pituitary-thyroid axis promote the adaptive responses of key osmoregulatory organs to freshwater (FW) environments. In the current study, we characterized circulating thyroxine (T4) and 3-3'-5-triiodothyronine (T3) levels in parallel with the outer ring deiodination (ORD) activities of deiodinases (dios) and mRNA expression of dio1, dio2, and dio3 in gill during the acclimation of Mozambique tilapia (Oreochromis mossambicus) to FW. Tilapia transferred from seawater (SW) to FW exhibited reduced plasma T4 and T3 levels at 6 h. These reductions coincided with an increase in branchial dio2-like activity and decreased branchial dio1 gene expression. To assess whether dios respond to osmotic conditions and/or systemic signals, gill filaments were exposed to osmolalities ranging from 280 to 450 mOsm/kg in an in vitro incubation system. Gene expression of branchial dio1, dio2, and dio3 was not directly affected by extracellular osmotic conditions. Lastly, we observed that dio1 and dio2 expression was stimulated by thyroid-stimulating hormone in hypophysectomized tilapia, suggesting that branchial TH metabolism is regulated by systemic signals. Our collective findings suggest that THs are involved in the FW acclimation of Mozambique tilapia through their interactions with branchial deiodinases that modulate their activities in a key osmoregulatory organ.

Twitter As a Noninvasive Bio-Marker for Trends in Liver Disease.

With the success of hepatitis C virus (HCV) direct-acting antiviral therapies, there has been a shift in research focus to the other major chronic liver diseases (CLDs). The use of social media, specifically Twitter, has become a popular platform for understanding public health trends and for performing health care research. To evaluate this, we studied the areas of public interest and social media trends of the following three major CLDs: hepatitis B virus (HBV), HCV, and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). Twitter activity data from January 1, 2013, through January 1, 2019, for HBV, HCV, and NAFLD/NASH were collected using the social media analytic tool Symplur Signals (Symplur LLC) software. Content and regression analyses were performed to understand and predict Twitter activity for each of the CLDs. Over the study period, there were 810,980 tweets generating 4,452,939,516 impressions. HCV tweet activity peaked in 2015 at 243,261 tweets, followed by a decline of 52.4% from 2015 to 2016 with a subsequent plateau through 2018. Meanwhile, NAFLD/NASH and HBV tweet activity has continued to increase, with projections that these two CLDs will surpass HCV by the second half of 2023 and 2024, respectively. Treatment and Management was the most popular content category for HCV and NAFLD/NASH, while Prevention was the most popular content category for HBV. Conclusion: Twitter is a useful social media tool to gauge public interest in liver disease over time. The information provided by Twitter can be used to identify gaps in public knowledge or highlight areas of interest that may need further research. Future studies on the use of Twitter in liver disease are warranted.

Diet-induced obesity in the selenocysteine lyase knockout mouse.

AIMS: Selenocysteine lyase (Scly) mediates selenocysteine decomposition. It was previously demonstrated that, upon adequate caloric intake (12% kcal fat) and selenium deficiency, disruption of Scly in mice leads to development of metabolic syndrome. In this study, we investigate the effect of a high-fat (45% kcal) selenium-adequate diet in Scly knockout (KO) mice on development of metabolic syndrome. Involvement of selenoproteins in energy metabolism after Scly disruption was also examined in vitro in the murine hepatoma cell line, Hepa1-6, following palmitate treatment. RESULTS: Scly KO mice were more susceptible to diet-induced obesity than their wild-type counterparts after feeding a high-fat selenium-adequate diet. Scly KO mice had aggravated hyperinsulinemia, hypercholesterolemia, glucose, and insulin intolerance, but unchanged inflammatory cytokines and expression of most selenoproteins, except increased serum selenoprotein P (Sepp1). Scly KO mice also exhibited enhanced hepatic levels of pyruvate and enzymes involved in the regulation of pyruvate cycling, such as pyruvate carboxylase (Pcx) and pyruvate dehydrogenase (Pdh). However, in vitro silencing of Scly in Hepa1-6 cells led to diminished Sepp1 expression, and concomitant palmitate treatment decreased Pdh expression. INNOVATION: The role of selenium in lipid metabolism is recognized, but specific selenium-dependent mechanisms leading to obesity are unclear. This study uncovers that Scly has a remarkable effect on obesity and metabolic syndrome development triggered by high-fat exposure, independent of the expression of most selenoproteins. CONCLUSION: Diet-induced obesity in Scly KO mice is aggravated, with effects on pyruvate levels and consequent activation of energy metabolism independent of selenoprotein levels.

Umbilical cord blood and placental mercury, selenium and selenoprotein expression in relation to maternal fish consumption.

Seafood is an important source of nutrients for fetal neurodevelopment. Most individuals are exposed to the toxic element mercury through seafood. Due to the neurotoxic effects of mercury, United States government agencies recommend no more than 340g (12oz) per week of seafood consumption during pregnancy. However, recent studies have shown that selenium, also abundant in seafood, can have protective effects against mercury toxicity. In this study, we analyzed mercury and selenium levels and selenoprotein mRNA, protein, and activity in placenta of a cohort of women in Hawaii in relation to maternal seafood consumption assessed with dietary surveys. Fish consumption resulted in differences in mercury levels in placenta and cord blood. When taken as a group, those who consumed no fish exhibited the lowest mercury levels in placenta and cord blood. However, there were numerous individuals who either had higher mercury with no fish consumption or lower mercury with high fish consumption, indicating a lack of correlation. Placental expression of selenoprotein mRNAs, proteins and enzyme activity was not statistically different in any region among the different dietary groups. While the absence of seafood consumption correlates with lower average placental and cord blood mercury levels, no strong correlations were seen between seafood consumption or its absence and the levels of either selenoproteins or selenoenzyme activity.

Effects of acclimation salinity on the expression of selenoproteins in the tilapia, Oreochromis mossambicus.

Selenoproteins are ubiquitously expressed, act on a variety of physiological redox-related processes, and are mostly regulated by selenium levels in animals. To date, the expression of most selenoproteins has not been verified in euryhaline fish models. The Mozambique tilapia, Oreochromis mossambicus, a euryhaline cichlid fish, has a high tolerance for changes in salinity and survives in fresh water (FW) and seawater (SW) environments which differ greatly in selenium availability. In the present study, we searched EST databases for cichlid selenoprotein mRNAs and screened for their differential expression in FW and SW-acclimated tilapia. The expression of mRNAs encoding iodothyronine deiodinases 1, 2 and 3 (Dio1, Dio2, Dio3), Fep15, glutathione peroxidase 2, selenoproteins J, K, L, M, P, S, and W, was measured in the brain, eye, gill, kidney, liver, pituitary, muscle, and intraperitoneal white adipose tissue. Gene expression of selenophosphate synthetase 1, Secp43, and selenocysteine lyase, factors involved in selenoprotein synthesis or in selenium metabolism, were also measured. The highest variation in selenoprotein and synthesis factor mRNA expression between FW- and SW-acclimated fish was found in gill and kidney. While the branchial expression of Dio3 was increased upon transferring tilapia from SW to FW, the inverse effect was observed when fish were transferred from FW to SW. Protein content of Dio3 was higher in fish acclimated to FW than in those acclimated to SW. Together, these results outline tissue distribution of selenoproteins in FW and SW-acclimated tilapia, and indicate that at least Dio3 expression is regulated by environmental salinity.

Disruption of the selenocysteine lyase-mediated selenium recycling pathway leads to metabolic syndrome in mice.

Selenium (Se) is an essential trace element used for biosynthesis of selenoproteins and is acquired either through diet or cellular recycling mechanisms. Selenocysteine lyase (Scly) is the enzyme that supplies Se for selenoprotein biosynthesis via decomposition of the amino acid selenocysteine (Sec). Knockout (KO) of Scly in a mouse affected hepatic glucose and lipid homeostasis. Mice lacking Scly and raised on an Se-adequate diet exhibit hyperinsulinemia, hyperleptinemia, glucose intolerance, and hepatic steatosis, with increased hepatic oxidative stress, but maintain selenoprotein levels and circulating Se status. Insulin challenge of Scly KO mice results in attenuated Akt phosphorylation but does not decrease phosphorylation levels of AMP kinase alpha (AMPKα). Upon dietary Se restriction, Scly KO animals develop several characteristics of metabolic syndrome, such as obesity, fatty liver, and hypercholesterolemia, with aggravated hyperleptinemia, hyperinsulinemia, and glucose intolerance. Hepatic glutathione peroxidase 1 (GPx1) and selenoprotein S (SelS) production and circulating selenoprotein P (Sepp1) levels are significantly diminished. Scly disruption increases the levels of insulin-signaling inhibitor PTP1B. Our results suggest a dependence of glucose and lipid homeostasis on Scly activity. These findings connect Se and energy metabolism and demonstrate for the first time a unique physiological role of Scly in an animal model.