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.

Intrauterine arsenic exposure induces glucose metabolism disorders in adult offspring by targeting TET2-mediated DNA hydroxymethylation reprogramming of HNF4α in developing livers, an effect alleviated by ascorbic acid.

Exposure to arsenic during gestation has lasting health-related effects on the developing fetus, including an increase in the risk of metabolic disease later in life. Epigenetics is a potential mechanism involved in this process. Ten-eleven translocation 2 (TET2) has been widely considered as a transferase of 5-hydroxymethylcytosine (5hmC). Here, mice were exposed, via drinking water, to arsenic or arsenic combined with ascorbic acid (AA) during gestation. For adult offspring, intrauterine arsenic exposure exhibited disorders of glucose metabolism, which are associated with DNA hydroxymethylation reprogramming of hepatic nuclear factor 4 alpha (HNF4α). Further molecular structure analysis, by SEC-UV-DAD, SEC-ICP-MS, verified that arsenic binds to the cysteine domain of TET2. Mechanistically, arsenic reduces the stability of TET2 by binding to it, resulting in the decrease of 5hmC levels in Hnf4α and subsequently inhibiting its expression. This leads to the disorders of expression of its downstream key glucose metabolism genes. Supplementation with AA blocked the reduction of TET2 and normalized the 5hmC levels of Hnf4α, thus alleviating the glucose metabolism disorders. Our study provides targets and methods for the prevention of offspring glucose metabolism abnormalities caused by intrauterine arsenic exposure.

Ginsenoside Rg1 inhibits dietary-induced obesity and improves obesity-related glucose metabolic disorders

Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.

Sensação subjetiva do zumbido pré e pós intervenção nutricional em alterações metabólicas / Tinnitus sensation pre and post nutritional intervention in metabolic disorders

BACKGROUND: different etiologies are related to tinnitus including metabolic disorders (blood glucose and lipids). AIM: the aim of this study was compare tinnitus severity by self-report measures pre and post nutritional intervention, using the Tinnitus Handicap Inventory. METHOD: participants of this study were twenty one male and female subjects, with ages ranging from 40 to 82 years. Inclusion criteria involved the presence of tinnitus and metabolic disorder diagnosed by laboratory exams. All subjects were submitted to a nutritional intervention program. Audiological evaluation and the Tinnitus Handicap Inventory were applied pre and post intervention. RESULTS: when comparing the presence of tinnitus pre and post intervention, data analysis indicates statistical difference concerning tinnitus sensation - 71.5 percent of the individuals referred less impact of tinnitus in daily activities. CONCLUSION: an important difference was observed concerning tinnitus influence in subject's life by self-report measures. A direct relation between tinnitus and metabolic disorders in cases related with this symptom was verified.

TEMA: diferentes etiologias estão relacionadas com a presença de zumbido, incluindo doenças metabólicas (glicêmicas e lipídicas). OBJETIVO: comparar o grau de severidade do zumbido por meio de medidas de auto-análise em sujeitos com alterações metabólicas pré e pós-intervenção nutricional, utilizando o Questionário de Gravidade do Zumbido. MÉTODO: vinte e um sujeitos, homens e mulheres, com idade entre 40 e 82 anos, participaram deste estudo. Critérios de inclusão abrangeram a presença de zumbido e de alteração metabólica diagnosticada por meio de exames laboratoriais. Todos os sujeitos foram submetidos a um programa de intervenção nutricional. A avaliação audiológia e o questionário de gravidade de zumbido foram aplicados pré e pós-intervenção. RESULTADOS: comparando os resultados pré e pós-intervenção os dados mostram uma diferença estatisticamente significante com relação à sensação do zumbido em 71,5 por cento dos sujeitos, os quais referiram menor impacto do zumbido nas atividades diárias. CONCLUSÃO: uma importante diferença foi observada com relação à influência do zumbido na vida do sujeito quando utilizadas as medidas de auto-análise. Verificou-se uma relação direta entre zumbido e alterações metabólicas em casos relacionados a estes sintomas.