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Recent studies suggest a key role for tissue aberrant expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and for tissue glucocorticoid excess in dysregulation of metabolism observed in diabetes and other metabolic disorders linked to central obesity. In an experiment carried out in 50 adult Wistar rats fed on diets containing sunflower oil, rapeseed oil, lard or cod liver oil at two levels (20 and 40% w/w), we were the first to show a beneficial inhibitory effect of all fats but one (sunflower oil) on hepatic 11β-HSD1 activity, given the moderately high consumption of fat (i.e. 20%).
The joint effects of energy restriction and age on adrenal glucocorticoid synthesis, liver signalling and liver thyroid hormone metabolism were examined. Adrenal type 1 11β-hydroxylase expression was chosen as a marker of adrenal steroidogenesis, liver 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor proteins as measures of glucocorticoid signalling, and liver type 1 and 3 deiodinase proteins as determinants of thyroid hormone metabolism. A nine-week study covered two groups (n = 21 each) of 17- and 45-week-old Sprague-Dawley male rats fed ad libitum and on diets with 20% or 40% energy deficit. Adrenal type 1 11β-hydroxylase mRNA and protein, hepatic type 1 11β-hydroxysteroid dehydrogenase level, glucocorticoid receptor and type 1 and 3 deiodinase protein levels, as well as plasma adrenocorticotropic hormone (ACTH) and corticosterone concentrations. Calorie restriction increased ACTH plasma concentrations and type 1 11β-hydroxylase protein levels were determined. Plasma ACTH and type 1 11β-hydroxylase protein were higher in older rats, while in the younger group, type 1 deiodinase protein exceeded the enzyme level in older rats. Calorie restriction decreased plasma corticosterone and type 1 11β-hydroxysteroid dehydrogenase only in older rats. Direct relationships between glucocorticoid receptors and type 1 and 3 deiodinases, as well as between type 3 deiodinase and type 1 11β-hydroxysteroid dehydrogenase, were observed. Taken together, the results indicate that responses of the rat pituitary-adrenal axis to calorie deficit are age-dependent. Moreover, the observed correlations suggest a mechanism linking an increase in glucocorticoid receptors with a reduction in peripheral thyroid hormone action resulting from a rise in the level of type 3 deiodinase.
Thyroid hormones (TH) are believed to participate in adaptation of the heart to dietary caloric restriction (CR). The effect of CR on cardiac thyroid hormone receptors α and β (TRα and TR β) has been hitherto insufficiently investigated, however, and with respect to the impact of CR on cardiac type 2 and 3 deiodinases (D2 and D3), we have not found any literature data. The aim of this study was to assess the effect of CR and age on thyroid hormone (TH) signalling (D2, D3, TR α and β) and myosin heavy chain β (BMHC) in the heart. The study was performed on 17-week- and 45-week-old male Sprague Dawley rats, fed ad libitum (AL) or restricted to 80% or 60% of AL energy intake. Plasma concentrations of TSH, total and free T3 and T4 (fT3 and fT4), protein levels of heart D2 and D3, THRα, THRβ, myosin heavy chain β (BMHC) mRNA expression and cardiac BMHC protein were determined. Morphological and endocrine parameters were influenced by age (fT3/T3, fT4/T4, THRα, BMHC protein), feeding level (TSH, T4, T3, BMHC mRNA), or by both age and feeding level (body weight, fT4, fT3). Caloric restriction reduced fT3, T4, and fT4 levels in both age groups, with additional decreases in TSH and T3 occurring in younger rats. Independently of age, cardiac BMHC expression was positively correlated with cardiac D3 and negatively with food intake and thyroid hormones. The most important finding of our study is that cardiac D3 and BMHC protein are, under conditions of differentiated dietary energy supply, directly related in both young and middle-aged rats.
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