Dataset Information

Dataset of liver proteins of eu- and hypothyroid rats affected in abundance by any of three factors: in vivo exposure to hexabromocyclododecane (HBCD), thyroid status, gender differences.

ABSTRACT: Male Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days and obtained data compared with a previous study in females, "Hexabromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats" (Miller et al., 2016) [1]. Specifically, proteomic investigation of liver protein patterns obtained by 2D-DIGE was performed and differences between animals groups recorded, based on the factors exposure, thyroid status and gender. All proteins with significantly changed abundance in any of these comparisons were identified by mass spectrometry. General, hormone and proteomic data of both the present and the previous studies are discussed in Miller et al. (2016) [1] and in "Gender specific differences in the liver proteome of rats exposed to hexabromocyclododecane (HBCD)" Miller et al. (2016) [2].

SUBMITTER: Miller I

PROVIDER: S-EPMC4992036 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Dataset of liver proteins of eu- and hypothyroid rats affected in abundance by any of three factors: in vivo exposure to hexabromocyclododecane (HBCD), thyroid status, gender differences.

Miller I I Renaut J J Cambier S S Murk A J AJ Gutleb A C AC Serchi T T

Data in brief 20160805

Male Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days and obtained data compared with a previous study in females, "Hexabromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats" (Miller et al., 2016) [1]. Specifically, proteomic investigation of liver protein patterns obtained by 2D-DIGE was performed and differences between animals groups recorded, based on t ...[more]

PMID: 27579339

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Project description:BackgroundHexabromocyclododecane (HBCD) is a high production volume brominated flame retardant added to building insulation foams, electronics, and textiles. HBCD is a commercial mixture (CM-HBCD) composed of three main stereoisomers: α-HBCD (10%), β-HBCD (10%), and γ-HBCD (80%). A shift from the dominant stereoisomer γ-HBCD to α-HBCD is detected in humans and wildlife.ObjectivesConsidering CM-HBCD has been implicated in neurodevelopment and endocrine disruption, with expected metabolism perturbations, we performed metabolomics on mice serum obtained during a window-of-developmental neurotoxicity to draw correlations between early-life exposures and developmental outcomes and to predict health risks.MethodsSix female C57BL/6 mice at postnatal day (PND) 10 were administered a single gavage dose of α-, γ-, or CM-HBCD at 3, 10, and 30 mg/kg. Nuclear magnetic resonance metabolomics was used to analyze 60 μL serum aliquots of blood collected 4 days post-oral exposure.ResultsInfantile mice exposed to α-, γ-, or CM-HBCD demonstrated differences in endogenous metabolites by treatment and dose groups, including metabolites involved in glycolysis, gluconeogenesis, lipid metabolism, citric acid cycle, and neurodevelopment. Ketone bodies, 3-hydroxybutyrate, and acetoacetate, were nonstatistically elevated, when compared with mean control levels, in all treatment and dose groups, while glucose, pyruvate, and alanine varied. Acetoacetate was significantly increased in the 10 mg/kg α-HBCD and was nonsignificantly decreased with CM-HBCD. A third ketone body, acetone, was significantly lower in the 30 mg/kg α-HBCD group with significant increases in pyruvate at the same treatment and dose group. Metabolites significant in differentiating treatment and dose groups were also identified, including decreases in amino acids glutamate (excitatory neurotransmitter in learning and memory) and phenylalanine (neurotransmitter precursor) after α-HBCD and γ-HBCD exposure, respectively.ConclusionsWe demonstrated that 4 days following a single neonatal oral exposure to α-, γ-, and CM-HBCD resulted in different serum metabolomic profiles, indicating stereoisomer- and mixture-specific effects and possible mechanisms of action.

Project description:BackgroundThe thyroid hormone triiodothyronine (T3) is known to affect energy balance. Recent evidence points to an action of T3 in the hypothalamus, a key area of the brain involved in energy homeostasis, but the components and mechanisms are far from understood. The aim of this study was to identify components in the hypothalamus that may be involved in the action of T3 on energy balance regulatory mechanisms.MethodsSprague Dawley rats were made hypothyroid by giving 0.025% methimazole (MMI) in their drinking water for 22 days. On day 21, half the MMI-treated rats received a saline injection, whereas the others were injected with T3. Food intake and body weight measurements were taken daily. Body composition was determined by magnetic resonance imaging, gene expression was analyzed by in situ hybridization, and T3-induced gene expression was determined by microarray analysis of MMI-treated compared to MMI-T3-injected hypothalamic RNA.ResultsPost mortem serum thyroid hormone levels showed that MMI treatment decreased circulating thyroid hormones and increased thyrotropin (TSH). MMI treatment decreased food intake and body weight. Body composition analysis revealed reduced lean and fat mass in thyroidectomized rats from day 14 of the experiment. MMI treatment caused a decrease in circulating triglyceride concentrations, an increase in nonesterified fatty acids, and decreased insulin levels. A glucose tolerance test showed impaired glucose clearance in the thyroidectomized animals. In the brain, in situ hybridization revealed marked changes in gene expression, including genes such as Mct8, a thyroid hormone transporter, and Agrp, a key component in energy balance regulation. Microarray analysis revealed 110 genes to be up- or downregulated with T3 treatment (± 1.3-fold change, p<0.05). Three genes chosen from the differentially expressed genes were verified by in situ hybridization to be activated by T3 in cells located at or close to the hypothalamic ventricular ependymal layer and differentially expressed in animal models of long- and short-term body weight regulation.ConclusionThis study identified genes regulated by T3 in the hypothalamus, a key area of the brain involved in homeostasis and neuroendocrine functions. These include genes hitherto not known to be regulated by thyroid status.

Project description:BackgroundThe incidence and prevalence of hypothyroidism are increasing and the threshold for the treatment of hypothyroid as well as individuals without evident thyroid disease with thyroid hormone is declining.ObjectiveTo investigate endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients in Italy, a country where different formulations of levothyroxine (LT4; tablet, liquid solution and soft-gel capsule) are available on the market.MethodsMembers of the Associazione Medici Endocrinologi (Italian Association of Clinical Endocrinologists) were invited to participate in a web-based survey investigating the topic.ResultsA total of 797 of 2,028 (39.3%) members completed all the sections of the survey; 98.7% declared that the treatment of choice for hypothyroidism is LT4. A significant minority (37.3%) indicated that LT4 may be considered in infertile euthyroid women seeking pregnancy and harbouring positive thyroperoxidase antibodies (TPOAb) and in goitre increasing in size (18.1%). LT4 + LT3 was considered by 43.2% for LT4-replaced patients and normal TSH, if they reported persistent symptoms. High percentages of respondents chose LT4 in a liquid solution or soft-gel capsules when taken together with other drugs interfering with LT4 absorption (81.8%), in patients with a history of celiac disease, malabsorption, lactose intolerance, intolerance to common excipients (96.6%), or unexplained poor biochemical control of hypothyroidism (74.4%), or in patients not able to adhere to ingesting LT4 fasted and/or separated from food/drink (98.9%). In total, 43.6% of responders would use LT4 in a liquid solution or soft-gel capsules for hypothyroid patients with biochemical euthyroidism on LT4, who had persistent symptoms.ConclusionsThe preferred treatment for hypothyroidism is LT4; LT3 + LT4 combination treatment is mainly considered in patients with persistent symptoms. A significant minority would offer LT4 to euthyroid women with positive TPOAb and infertility and to euthyroid patients with progressive simple goitre. Alternative LT4 formulations like liquid solution or soft-gel capsules are largely reserved for specific conditions (interfering drugs, actual or suspected malabsorption, inability to take LT4 in the fasting state, unexplained poor biochemical control of hypothyroidism).

Dataset Information

Dataset of liver proteins of eu- and hypothyroid rats affected in abundance by any of three factors: in vivo exposure to hexabromocyclododecane (HBCD), thyroid status, gender differences.

Publications

Dataset of liver proteins of eu- and hypothyroid rats affected in abundance by any of three factors: in vivo exposure to hexabromocyclododecane (HBCD), thyroid status, gender differences.

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