Triiodothyronine(T3) neogenesis in lean and obese LAN-cp rats (original) (raw)
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Triiodothyronine(T3) neogenesis in lean and obese rats
Biochemical and Biophysical Research Communications, 1986
Pre-obese LA/N-cp rats consumed more food and gained weight more rapidly than their lean littermates, and measures of adipose tissue depots indicated that the excess weight was deposited principally as carcass fat. Serum T9 concentrations and resting metabolic rates were lower in corpulent than in lean animals, consistent with a greater efficiency of weight gain in those animals. In vitro measures of T9 neogenesis from T4 were lower in corpulent than in lean animals in liver, kidney, and skeletal muscle and greater in interscapular brown adipose tissue. The intracellular generation of T8 from T4 is a fundamental component of the normal adaptive response to alterations in diet and environment, and is an essential prerequisite for the expression of non-shivering thermogenesis. These results are consistent with a functional impairment in the activity of the enzyme T4-5'-deiodinase in peripheral tissues, and suggest that this impairment is contributory if not causative of obesity in this strain of rat.
Endocrinology, 2010
This study investigated the effects of obesity induced by high-fat (HF) diet on thyroid function and whole-body energy balance. To accomplish that, we assessed the effects of 8 wk of HF diet on several parameters of hypothalamus-pituitary-thyroid axis function. Serum total T4 and T3, rT3, and TSH, the activity of type 1 and type 2 deiodinases in central and peripheral tissues were determined. Also, we measured in vivo energy balance, substrate partitioning, and markers of leptin resistance. Here we provide novel evidence that prolonged positive energy balance acquired by feeding a HF diet induced hyperactivation of the hypothalamus-pituitary-thyroid axis, which was characterized by 2.24-, 1.6-, and 3.7-fold elevations in hypothalamic TRH expression, thyroid iodide uptake, and serum TSH, respectively. Serum T4 and T3 were normal together with augmented deiodinase type 1 activity in liver (1.3-fold) and kidney (1.2-fold) and increased (1.5-fold) serum rT3 in HF rats. Despite no increa...
The Biochemical journal, 1988
Brown adipose tissue iodothyronine 5'-deiodinase activity is significantly lower in 17-day pregnant rats compared with virgin controls and remains low during late pregnancy and lactation. It fully recovers with abrupt weaning, but only partially with spontaneous weaning. Even though this profile of changes is remarkably in step with the known pattern of modifications in brown fat thermogenesis during the breeding cycle, the lowered iodothyronine 5'-deiodinase activity appearing between days 15 and 17 of pregnancy occurs earlier than the reduction in brown adipose tissue thermogenesis. Brown fat 3,3',5-tri-iodothyronine content is also reduced in late pregnant, early and mid-lactating rats, most probably as a consequence of the lowered 5'-deiodination of thyroxine in situ. Acute insulin treatment increases brown fat iodothyronine 5'-deiodinase activity in virgin animals as well as in late-pregnant and lactating rats, despite the lowered basal enzyme activity level...
Iodothyronine 5′-deiodinase activity in rat brown adipose tissue during development
Biochimica et Biophysica Acta (BBA) - General Subjects, 1987
lodothyronine 5'-deiodinase activity in rat brown adipose tissue has a characteristic pattern of developmental changes that is completely different from that of the liver. Fetal brown fat exhibits an extremely high iodothyronine 5'-deiodinase activity that is approx. 10-fold that in adult rats. Even though brown fat iodothyronine 5'-deiodinase activity falls suddenly at birth, there is a new peak in the activity around days 5-7 of life, whereas it remains very low afterwards. Just after birth, brown adipose tissue iodothyronine 5'-deiodinase activity is already capable of stimulation by noradrenaline. The postnatal peak in brown fat iodothyronine 5'-deiodinase correlates with the known increase in the thermogenic activity of the tissue in the neonatal rat, thus reinforcing the suggestion that local 3',3,5-triiodothyronine generation could be an important event related to thermogenesis in brown adipose tissue. However, the high fetal activity was only slightly related to the thermogenic activity of brown fat. Moreover, the increased iodothyronine 5'-deiodinase activity of brown adipose tissue during fetal and neonatal life suggests a substantial contribution by brown fat in the overall extrathyroidal 3',3,5-triiodothyronine production in these physiological periods.
International Journal of Obesity, 2011
Differentiation and metabolism of adipose tissue are modulated by thyroid hormones (THs), but relatively little is known about the metabolism of THs in this tissue. Expression of the genes for type I iodothyronine 5 0 -deiodinase (D1), leptin (LEP) and stearoyl-CoA desaturase 1 (SCD-1) was evaluated in omental (OM) and subcutaneous (SC) fat using a cohort of 70 humans. Activities of iodothyronine deiodinases (D1, D2 and D3) were assessed in a randomly selected subpopulation of 19 subjects. D1 expression was upregulated in both OM (P ¼ 0.011) and SC (P ¼ 0.003) fat of obese subjects. Concomitantly, OM (P ¼ 0.002) and SC (P ¼ 0.028) LEP expression were increased in obesity, associated with both D1 mRNA (r ¼ 0.315, P ¼ 0.014) and activity (r ¼ 0.647, P ¼ 0.023) and inversely related to SCD-1 (r ¼ À0.266, P ¼ 0.034) expression in SC fat. Also D1 (but not D2 and D3) activity was increased in OM (Bfourfold, P ¼ 0.010) and SC (Beightfold, P ¼ 0.004) fat of obese when compared with non-obese subjects and correlated in both OM (r ¼ 0.528, P ¼ 0.036) and SC (r ¼ 0.749, P ¼ 0.005) fat with body mass index. Our results document increased D1 gene expression and activity in adipose tissue of obese humans and suggest a role of 3,5,3 0 -triiodo-L-thyronine formed by D1 in response to leptin in the modulation of adipose tissue metabolism.
3,5-Diiodo-L-Thyronine Activates Brown Adipose Tissue Thermogenesis in Hypothyroid Rats
PLOS ONE, 2015
3,5-diiodo-l-thyronine (T2), a thyroid hormone derivative, is capable of increasing energy expenditure, as well as preventing high fat diet-induced overweight and related metabolic dysfunction. Most studies to date on T2 have been carried out on liver and skeletal muscle. Considering the role of brown adipose tissue (BAT) in energy and metabolic homeostasis, we explored whether T2 could activate BAT thermogenesis. Using euthyroid, hypothyroid, and T2-treated hypothyroid rats (all maintained at thermoneutrality) in morphological and functional studies, we found that hypothyroidism suppresses the maximal oxidative capacity of BAT and thermogenesis, as revealed by reduced mitochondrial content and respiration, enlarged cells and lipid droplets, and increased number of unilocular cells within the tissue. In vivo administration of T2 to hypothyroid rats activated BAT thermogenesis and increased the sympathetic innervation and vascularization of tissue. Likewise, T2 increased BAT oxidative capacity in vitro when added to BAT homogenates from hypothyroid rats. In vivo administration of T2 to hypothyroid rats enhanced mitochondrial respiration. Moreover, UCP1 seems to be a molecular determinant underlying the effect of T2 on mitochondrial thermogenesis. In fact, inhibition of mitochondrial respiration by GDP and its reactivation by fatty acids were greater in mitochondria from T2-treated hypothyroid rats than untreated hypothyroid rats. In vivo administration of T2 led to an increase in PGC-1α protein levels in nuclei (transient) and mitochondria (longer lasting), suggesting a coordinate effect of T2 in these organelles that ultimately promotes net activation of mitochondrial biogenesis and BAT thermogenesis. The effect of T2 on PGC-1α is similar to that elicited by triiodothyronine. As a whole, the data reported here indicate T2 is a thyroid hormone derivative able to activate BAT thermogenesis.
Endocrinology, 1998
In euthyroid rats, maximal sympathetic nervous system stimulation (e.g. during cold exposure) results in a 3-to 4-fold increase in brown adipose tissue lipogenesis, a response that is blunted in hypothyroid rats. To further investigate this phenomenon, the role of local type II 5Ј-deiodinase (5Ј-DII) was studied in freshly isolated brown adipocytes. In a typical experiment, 1.5 ϫ 10 6 cells were incubated for up to 48 h in a water-saturated 5% CO 2-95% O 2 atmosphere. After incubation with medium alone or with different concentrations of T 4 , T 3 , and/or norepinephrine (NE), lipogenesis was studied by measuring 1) the rate of fatty acid synthesis as reflected by 3 H 2 O incorporation into lipids and 2) the activity of key ratelimiting enzymes, i.e. acetyl coenzyme A carboxylase and malic enzyme, and the results are reported in terms of DNA content per tube. Lipogenesis decreased progressively over time (ϳ40%) when no additions were made to the incubation medium. T 4 or T 3 partially prevented that inhibition at physiological concentrations (65 ϫ 10 Ϫ9 and 0.77 ϫ 10 Ϫ9 M, respectively), whereas a receptor-saturating concentration of T 3 (154 ϫ 10 Ϫ9 M) doubled the lipogenesis rate. The addition
Previous studies have shown that alterations in thyroid status may lead to changes in serum leptin and adiponectin, both in humans and rodents. The mechanisms, especially for adiponectin, are unclear. In the present study, we investigated the eff ect of triiodothyronine (T3) on the expression of adiponectin mRNA and the release of leptin and adiponectin by white adipose tissue (WAT) explants obtained from epididymal (visceral) or inguinal (subcutaneous) depots from normal rats. We also analyzed the eff ects of other known regulators of adiponectin and leptin release, such as rosiglitazone and dexamethasone. T3 acted directly at rat WAT explants in a depot-specifi c manner and in a unique fashion to each hormone. T3 was able to inhibit leptin release only by epididymal explants, and to reduce adiponectin mRNA expression only in inguinal explants. However, T3 was incapable of modifying adiponectin release by both explants. Additionally, rosiglitazone exhibited an inhibitory eff ect on adiponectin release by both WAT explants, even though adiponectin mRNA was importantly upregulated only in inguinal explants. Rosiglitazone acted as an inhibitor of leptin release by both studied fat depots, while only epididymal explants responded to the stimulatory eff ect of dexamethasone on leptin release. Therefore, the present model of isolated rat white adipose tissue explants highlights the fact that the regulation of hormonal production by white adipose tissue depends on the type of depot and its anatomical location. In this context, our results show for the fi rst time a potential inhibitory eff ect of T3 on adiponectin mRNA expression specifi cally on WAT from a subcutaneous depot.