Morphological and functional changes in rat thyroid gland after a year following chronic exposure to low and intermediate doses of γ-radiation.

INTRODUCTION: Thyroid function depends on iodine uptake by the body as well as on exposure to various harmful environmental hazards (stress, ionizing radiation). AIM: The aim of the work was to assess the effect of exposure to low and intermediate doses of external γ-radiation on the thyroid structure and function in young female rats at remote periods after radiation. MATERIALS AND METHODS: Forty female rats were used to study remote effects of external γ-radiation exposure during 20 d (at daily doses of 0.1, 0.25 and 0.5 Gy) on the functional activity (levels of thyroid hormones, iodine metabolism) and the morphological structure of the rat thyroid) after 12 months following the radiation exposure. RESULTS: An increase in thyroid mass and a decrease in total thyroid protein concentration along with a reduction of blood T3 and T4 was shown only in rat groups exposed to 0.25 and 0.5 Gy. Both the concentration of total iodine and its protein-bound fraction (1.2-1.4 fold, p < .01) and the protein-bound to total iodine ratio were decreased in the thyroids of all irradiated animals. The 0.1-Gy group showed elevated thyroperoxidase (TPO) activity along with increased catalase activity, which may indicate the activation of iodine oxidation by thyrocytes. Only the 0.5-Gy group demonstrated reduced urinary excretion of iodine (2.1 fold, p < .01).The reduction of thyroid function at radiation doses of 0.25 and 0.5 Gy was characterized by a microfollicular structure and the development of atrophic changes in the parenchyma, desquamation of thyroid epithelium and an increase in epithelium proliferation. The diameter of the thyrocyte nuclei was increased in rats exposed to 0.25 and 0.5 Gy, which indicates functional tension of thyrocytes. CONCLUSION: Our research shows that after a year, the exposure to external γ-radiation of 0.1, 0.25 and 0.5-Gy caused changes in the structure and function of the rat thyroid which are manifested by the development of hypothyroiditis (0.5 Gy), 'subclinical' hypothyroiditis (0.25 Gy) and functional tension of thyrocytes. The mechanisms of thyroid dysfunction - impaired- uptake of iodine and its organification against the background of activation of free radical processes - suggest disturbances in the function of the sodium/iodide symporter (NIS), TPO and thyroglobulin synthesis. In contrast to the intermediate doses, the effects of the 0.1-Gy dose were mostly found at the remote periods compared to the earlier periods (180 days).

Role of UCP1 Gene Variants in Interethnic Differences in the Development of Cardio-Metabolic Diseases.

Cardio-metabolic diseases (CMDs) comprise a cluster of risk factors that contribute to chronic pathological conditions with adverse consequences for cardiovascular function and metabolic processes. A wide range of CMD prevalence rates among different ethnic groups has been documented. In view of accumulated evidence, there is a trend toward increasing CMD prevalence rates in Eastern Europe and Western Asia. Numerous studies have revealed an association between uncoupling protein 1 (UCP1) gene variants and CMDs. UCP1 activity is essential for brown adipose tissue (BAT)-mediated thermogenesis. Experimental animal studies and epidemiological studies in humans highlight the significance of BAT-mediated thermogenesis in protecting against obesity and maintaining a lean phenotype. We hypothesize that the genetic variation in UCP1 gene expression observed among different ethnic groups could contribute to the ethnic-specific predisposition to CMD development. Constructing such prevalence maps of UCP1 gene variants could contribute significantly into identifying high-risk ethnic groups predisposed to the development of CMDs, and further shaping public health policies by the improvement of existing preventive and management strategies.

Chronic l-menthol-induced browning of white adipose tissue hypothesis: A putative therapeutic regime for combating obesity and improving metabolic health.

INTRODUCTION: Obesity constitutes a serious global health concern reaching pandemic prevalence rates. The existence of functional brown adipose tissue (BAT) in adult humans has provoked intense research interest in the role of this metabolically active tissue in whole-body energy balance and body weight regulation. A number of environmental, physiological, pathological, and pharmacological stimuli have been proposed to induce BAT-mediated thermogenesis and functional thermogenic BAT-like activity in white adipose tissue (WAT), opening new avenues for therapeutic strategies based on enhancing the number of beige adipocytes in WAT. HYPOTHESIS: Recent evidence support a role of l-menthol cooling, mediated by TRPM8 receptor, on UCP1-dependent thermogenesis and BAT-like activity in classical WAT depots along with the recruitment of BAT at specific anatomical sites. l-Menthol-induced BAT thermogenesis has been suggested to occur by a ß-adrenergic-independent mechanism, avoiding potential side-effects due to extensive ß-adrenergic stimulation mediated by available beta receptor agonists. l-Menthol has been also linked to the activation of the cold-gated ion channel TRPA1. However, its role in l-menthol-induced UCP1-dependent thermogenic activity in BAT and WAT remains undetermined. White adipose tissue plasticity has important clinical implications for obesity prevention and/or treatment because higher levels of UCP1-dependent thermogenesis can lead to enhanced energy expenditure at a considerable extent. We hypothesize that chronic dietary l-menthol treatment could induce TRPM8- and TRPA1-dependent WAT adaptations, resembling BAT-like activity, and overall improve whole-body metabolic health in obese and overweight individuals. CONCLUSIONS: The putative impact of chronic l-menthol dietary treatment on the stimulation of BAT-like activity in classical WAT depots in humans remains unknown. A detailed experimental design has been proposed to investigate the hypothesized l-menthol-induced browning of WAT. If our hypothesis was to be confirmed, TRPM8/TRPA1-induced metabolic adaptations of WAT to BAT-like activity could provide a promising novel therapeutic approach for increasing energy expenditure, regulating body weight, and preventing obesity and its related co-morbidities in humans.