Deiodinase In Brown Adipose Tissue Research Articles

Biliary diversion increases resting energy expenditure leading to decreased blood glucose level in mice with type2 diabetes.

Aims/IntroductionType 2 diabetes mellitus is a group of metabolism abnormalities in carbohydrates and energy. Our aim was to investigate resting energy expenditure (REE) and blood glucose changes after biliary diversion in mice with diabetes.Materials and MethodsMale mice with diabetes were randomly divided into biliary diversion and sham groups. REE was detected by indirect calorimetry, the levels of fasting blood glucose, total bile acids and triiodothyronine were analyzed. After mice were killed, the weight amount of brown adipose tissue (BAT) and gastrocnemius was measured, and the expression level of G protein‐coupled bile acid receptor and type 2 iodothyronine deiodinase in BAT and gastrocnemius were examined.ResultsThe two groups of mice were pair‐fed, the bodyweights (P < 0.001) and the fasting blood glucose level (P < 0.001) in the biliary diversion group significantly decreased 24 weeks after surgery. The intraperitoneal glucose tolerance test (P = 0.035) and oral glucose tolerance test (P = 0.027) showed improvement in glucose tolerance after surgery. The REE level significantly increased 24 weeks after surgery (P = 0.005), the levels of total bile acids (P = 0.014) and triiodothyronine (P < 0.001) increased at the 24th postoperative week. The weight ratio of BAT (P = 0.038) and gastrocnemius (P = 0.026) in the biliary diversion group were higher than that in the sham group. The expression of G protein‐coupled bile acid receptor in BAT (P < 0.001) and gastrocnemius (P = 0.003) were upregulated after surgery, and the type 2 iodothyronine deiodinase expression also increased in BAT (P = 0.015) and gastrocnemius (P = 0.015).ConclusionsThe REE level increased and the glucose metabolism improved in mice with diabetes after biliary diversion.

Psychobiological assessment in offspring of Wistar rats supplemented with sodium selenite during the period of pregnancy and lactation (684.13)

The objective of this study was to evaluate the possible occurrence of behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. Two groups were treated during pregnancy and lactation with: saline or sodium selenite at a dose of 1 mg/kg through oral route. Thyroid status was determined by serum analysis of thyroid hormones and for gene expression analyzes, we used RT‐qPCR. At 60 days‐old, the offspring underwent a behavioral assessment in an open field test, elevated plus maze test, object recognition task and swimming forced test for five minutes. Statistical analysis was performed by t student test, considering the significant differences between means at p &lt;0.05. According to the results, it was demonstrated that supplementation with Se causes increased levels of triiodothyronine (25%, p = 0.0001) and the expression of type 2 deiodinase in brown adipose tissue (351%, p = 0.002). Moreover, Se treatment promotes reduction of TPH2 expression (12%, p = 0.007), but increases the levels of mRNA for TH (200%, p = 0.002) in the hippocampus. It was also found that the offspring of females supplemented with Se have higher locomotor activity (50%, p = 0.004) and more rearing (77%, p &lt;0.0001) in the open field test. In the elevated plus maze, the treated group had higher time spent in the open arms (143%, p = 0.005). Finally, through the object recognition task, the programmed offspring had a higher absolute index of discrimination (230%, p = 0.02). The results demonstrate that maternal supplementation with sodium selenite affects the physiological systems involved with learning and expression of affective behavior in adulthood. Therefore, we believe that the behavioral profile observed can be related to neurochemical changes during the critical period of the central nervous system ontogeny.Grant Funding Source: FAPERJ/CNPq

Metabolic profile Assessment in offspring of wistar rats treated during pregnancy and lactation with sodium selenite

The essential micronutrient selenium has been linked to property exhibiting insulin‐mimetic effects in metabolism. On the other hand, some studies shows that selenium supplementation at high doses can increase the incidence risk of diabetes. Thereby, due to an inverse correlation between the serum selenium concentration and the progressing gestational period, the objective here was evaluating offspring metabolism of female Wistar rats treated during pregnancy and lactation with sodium selenite. For this purpose, two groups (n=6 each and ~ 250g) of female Wistar rats were underwent to the following treatments: isotonic saline or sodium selenite (1mg/kg, p.o). Our results indicate that treated group, after weaning, had higher expression of type 2 deiodinase in brown adipose tissue than control. Moreover, the programmed offspring had higher milk intake and had an increased lipid oxidation. Therefore, we conclude that selenium supplementation during pregnancy and lactation alters offspring metabolic profile. In this context, we conjecture that possible selenium induced insulin resistance in offspring can be caused by thyroid hormones genomic and non genomic actions.Support: FAPERJ &amp; CNPq.

Uncoupling protein mRNA, mitochondrial GTP-binding, and T 4 5′-deiodinase activity of brown adipose tissue in Daurian ground squirrel during hibernation and arousal

The mRNA level of uncoupling protein (UCP) specific for brown adipose tissue (BAT) in Daurian ground squirrel, was detected by using a [ 32P]-labeled oligonucleotide probe. The UCP concentration in mitochondria was indirectly determined by titration with its specific ligand [ 3H]-labeled GTP. Type II T 4 5′-deiodinase of BAT was assayed concomitantly. We found two species of mRNA for UCP with lengths of about 1.9 and 1.5 kb, respectively, both occurring in almost the same concentration. UCP mRNA content was elevated significantly during hibernation, but the UCP concentration did not change compared with that of nonhibernating controls kept at room temperature. When hibernating squirrels were aroused, the UCP mRNA remained at the elevated level as during hibernation, but the UCP concentration increased in comparison with that of nonhibernating controls or during hibernating. Changes in T 4 5′-deiodinase activity in BAT were similar to the variations of the UCP mRNA level. These results suggest that the activation of T 4 5′-deiodinase in BAT may be an important factor for the up-regulation and maintenance of UCP mRNA content needed for the synthesis of sufficient UCP to acquire the thermogenic capacity for arousal from hibernation.

Sudden infant death syndrome (SIDS): Disordered brown fat metabolism and thermogenesis

Foster found areas with the highest incidence of SIDS in USA in 1983–1984 coincided with the highest areas recorded with the highest incidence of goitre in First World War troops (1). Reid compared the two populations described as having the highest incidence of SIDS worldwide. Both were selenium deficient areas (King County WA, USA and Canterbury, New Zealand). Besides being a selenium livestock responsive area, Canterbury school children, prior to 1925, had a 56% incidence of goitre (2–6). Brown adipose tissue (BAT) synthesises fatty acids from glucose. BAT is a major tissue in fatty acid metabolism for the generation of heat (7). BAT has the specific property of converting thyroxine (T 4) to triodothyronine (T 3) via Type II deiodinase enzyme. There is a many fold increase in the activity of this deiodinase in BAT after exposure of rats to sudden cold, which is greatly impaired in selenium deficient animals (7). The accepted picture of SIDS worldwide is that there is an increased incidence in infants of young smoking mothers. The incidence peaks in the second and third month of life, in winter and as latitude increases.

Effects of Cold Acclimation and Fasting on Thyroxine 5'-Deiodinase in Brown Adipose Tissue of ob/ob Mice

Gradual acclimation to mild cold for 6 weeks increases the total activity of thyroxine 5'-deiodinase in brown adipose tissue (BAT) of genetically obese (ob/ob) mice to a level greater than that in similarly acclimated lean mice. This increase is largely due to the growth of the BAT in the ob/ob mouse, because specific activity of the enzyme is only slightly increased. In similarly cold-acclimated lean mice, the specific activity of thyroxine 5'-deiodinase was not altered. BAT mitochondrial GDP binding increased to the same high level in the gradually cold-acclimated ob/ob mouse as in cold-acclimated lean mice. We conclude that the growth and maintenance of BAT in the cold-acclimated ob/ob mouse, as in the cold-acclimated lean mouse, does not require greatly increased activity of thyroxine 5'-deiodinase. Fasting for 48 hr did not alter thyroxine 5'-deiodinase activity of BAT in either lean or ob/ob mice. The fasting-induced increase in activity seen by others in lean mice is probably due to thermoregulatory stimulation of BAT occasioned by the low environmental temperature at which the fasting occurred.

Role of the sympathetic innervation in the cold-induced activation of 5′-deiodinase in brown adipose tissue of the Djungarian hamster

The importance of the sympathetic innervation in the regulation of 5'-deiodinase activity in the interscapular brown adipose tissue (BAT) of the Djungarian hamster was studied. Interscapular BAT of Djungarian hamsters was either unilaterally or bilaterally denervated, and thereafter the animals were maintained at thermoneutral temperature or exposed to 0 degree C for 24 h. Denervation reduced the norepinephrine content to 2-10% of the level in the control groups. Unilateral denervation was as effective as bilateral denervation in depressing the norepinephrine content of the interscapular BAT. Cold exposure for 24 h resulted in a pronounced 5'-deiodinase activation. Denervation reduced, but did not completely prevent, the cold-induced increase in 5'-deiodinase activity. The basal level of 5'-deiodinase activity at thermoneutral temperature was not reduced by denervation. We conclude that cold-induced activation of BAT 5'-deiodinase primarily depends on the intact sympathetic innervation.

Capsaicin desensitization induces atrophy of brown adipose tissue in rats

Interscapular brown adipose tissue (BAT) of capsaicin-desensitized (Cap-Des) rats is atrophied, having a lower wet weight, a reduced total protein content, and as little as 10% of the normal content of uncoupling protein (UCP). Because the mitochondrial concentration of UCP, relative to other mitochondrial proteins, is not altered in Cap-Des rats, it is concluded that most of the mitochondria of BAT of Cap-Des rats have been lost. Consistent with this interpretation is a reduction of almost 40% of the overall thermogenic response to infused norepinephrine by anesthetized Cap-Des rats. Feeding a palatable diet had a delayed thermogenic effect and no trophic effect on BAT of Cap-Des rats. Food selection and intake were normal in Cap-Des rats, and diet-induced weight gain was the same as in control rats. Exposure of Cap-Des rats to cold for 1 or 7 days exerted a normal thermogenic effect on BAT but a delayed trophic effect. The cold-induced increase in thyroxine 5'-deiodinase in BAT occurred normally. Cap-Des rats were hypothermic at 1 day but normothermic by 7 days of cold exposure. The concentration of thyroid hormones in their blood was normal. It is suggested that the depletion of sensory neuropeptides in BAT presumed to be brought about by Cap-Des results either in loss of a trophic influence on mitochondriogenesis in BAT or in lack of an inhibitory influence on mitochondrial breakdown in BAT and leads to atrophy of BAT in rats living at 26 degrees C and an impaired response to stimulation by diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic effects on thyroxine 5'-deiodinase in brown adipose tissue of lean and ob/ob mice

Genetically obese, ob/ob, mice have an impaired capacity to increase the level of thyroxine 5'-deiodinase (T5'D) in their brown adipose tissue (BAT) when they are exposed to cold. Yet they are able to secrete norepinephrine (NE) from the nerves of their BAT in response to cold and are apparently refractory to this action of NE. The principal objective was to find out whether injected NE could increase T5'D in BAT of the ob/ob mouse. A secondary objective was to elucidate the nature of the adrenergic receptor(s) involved in this response in lean and ob/ob mice. Injection of NE increased T5'D in BAT of lean mice within 3 h. It also increased T5'D in BAT of ob/ob mice but to a lesser extent. Basal T5'D activity in BAT of ob/ob mice was greater than that seen in BAT of lean mice because of the greater size of the tissue. Neither isopropylnorepinephrine nor phenylephrine alone could increase T5'D activity, but a combination increased it almost as well as did NE, although to a lesser extent in ob/ob mice than in lean mice. Both a beta-adrenergic antagonist (propranolol) and an alpha 1-adrenergic antagonist (prazosin) could inhibit the effect of NE. The acute effect of NE on metabolic rate of intact mice also involves an action of both beta- and alpha 1-adrenergic receptors. The beta-adrenergic component appears to be defective in the ob/ob mouse.

Defective regulation of thyroxine 5'-deiodinase in brown adipose tissue of ob/ob mice

Genetically obese (ob/ob) and lean (+/?) mice were exposed to a cold (14 degrees C) environment for 1, 3, 6, 12, 16, or 24 h or remained in a warm (28 degrees C) environment. In ob/ob mice the increase in brown adipose tissue (BAT) thermogenesis (mitochondrial GDP binding) was low and the increase in thyroxine 5'-deiodinase (T5'D) was delayed; there was a reduced increase in serum 3,5,3'-triiodothyronine (T3) level and these mice became hypothermic. Content of uncoupling protein (UCP) was low in BAT of obese mice and no cold-induced increase occurred. Adrenalectomy of obese mice before exposure to cold (14 degrees C) improved defective thermogenic response of BAT and thermoregulation, restored to normal the increases in T5'D activity and serum T3 level, and promoted an exaggerated increase in UCP content, detectable after only 6 h. Adrenalectomy of cold-exposed lean mice did not alter thermoregulation, the increase in BAT T5'D activity, or the increase in serum T3 but enhanced the thermogenic response and allowed a higher UCP content in BAT of cold-exposed mice. We conclude that suppression of the cold-induced increase in T5'D activity in BAT can be added to the other known corticosterone-dependent anomalies of the ob/ob mouse. We speculate that lack of the cold-induced increase in T5'D in BAT of the ob/ob mouse prevents the normal participation of T3 in the trophic response of BAT to cold and underlies the abnormality in this response.

Thyroxine 5′-deiodinase in brown adipose tissue of the cynomolgus monkey Macaca fascicularis

Brown adipose tissue was identified in axillary, interscapular, subscapular, and cervical fat deposits of male and female cynomolgus monkeys (Macaca fascicularis) by histological and immunological techniques. Histology included staining of mitochondria with a Novelli stain and identification of mitochondria-rich multilocular cells. Immunological detection involved separation of homogenate proteins by sodium dodecyl sulphate--polyacrylamide gel chromatography, blotting on to nitrocellulose membranes, and identification of the specific uncoupling protein, unique to brown adipose tissue, with an antiserum to purified hamster uncoupling protein followed by detection with 125I-labelled protein A. The activity of thyroxine 5'-deiodinase in monkey brown adipose tissue homogenates was much higher than that seen previously in brown adipose tissue of rats, mice, and hamsters. This is the first demonstration of the presence of this enzyme in brown adipose tissue of a primate species.

Thyroxine 5'-deiodinase in brown adipose tissue of myopathic hamsters.

Myopathic Syrian hamsters (BIO 14.6) have less brown adipose tissue (BAT) than normal. The trophic response of this tissue to cold is smaller than normal and trophic responses to diet and to photoperiod are absent. The objective was to find out whether activity of thyroxine 5'-deiodinase in their BAT was increased normally in response to cold and thus whether a defect in endogenous production of 3,5,3'-triiodothyronine might underlie the attenuated trophic response. The effect of feeding a high-fat diet on activity of 5'-deiodinase was also studied. Cold acclimation increased thyroxine 5'-deiodinase activity in BAT of the myopathic hamster, but the total remained smaller than normal because of the smaller size. The cold-induced increase in concentration of mitochondrial uncoupling protein was also smaller than normal. The level of serum 3,5,3'-triiodothyronine was low in myopathic hamsters and remained lower than normal when they were cold-exposed or cold acclimated. Feeding the high-fat diet to myopathic hamsters resulted in a greater than normal suppression of thyroxine 5'-deiodinase activity than in normal hamsters; the normal increases in protein content and in concentration of mitochondrial uncoupling protein were absent. We conclude that the defective trophic response of BAT of the myopathic hamster is not secondary to defective regulation of its thyroxine 5'-deiodinase activity because this activity does not appear to be obligatorily linked to hypertrophy of BAT. The low level of serum 3,5,3'-triiodothyronine in the myopathic hamster may be secondary to reduced capacity for peripheral thyroxine deiodination in its BAT.

Defective cold-induced stimulation of thyroxine 5′-deiodinase in brown adipose tissue of the genetically obese ( [formula omitted]) mouse

Exposure of a normal lean mouse to cold (14°C) for 12 h increases the activity of thyroxine 5′-deiodinase in brown adipose tissue 26-fold. In contrast, exposure of the genetically obese, ob ob , mouse to cold results in little more than a doubling of thyroxine 5′-deiodinase activity. The physiological significance of endogenous 3,5,3′-triiodothyronine production in brown adipose tissue is not understood. However, it seems likely that defective cold-induced stimulation of the 5′-deiodinase in brown adipose tissue of the ob ob mouse might cause a relatively hypothyroid state of the tissue. Thyroid hormone is known to be required for a normal thermogenic response of brown adipose tissue to noradrenaline. It is suggested that the defect in the response of the 5′-deiodinase in the ob ob mouse could contribute to the defective thermogenic response of brown adipose tissue to cold-exposure and to noradrenaline.