Dopamine β-hydroxylase and cytochrome oxidase activities in brown adipose tissue of newborn rats following sympathectomy with 6-hydroxydopamine

1977 ◽  
Vol 55 (3) ◽  
pp. 695-699 ◽  
Author(s):  
W. A. Behrens ◽  
Florent Depocas

Dopamine-β-hydroxylase (DBH) (EC 1.14.17.1) activity is present in the interscapular brown adipose tissue (IBAT) as early as 2 days of age in the white rat. The specific and the total activities of this enzyme, as well as those of cytochrome oxidase (COX) (EC 1.9.3.1) in IBAT increase up to at least 20 days of age. Daily administration of 6-hydroxydopamine (6-OHDA) between the second and the twelfth day after birth does not significantly alter IBAT weight gain relative to untreated controls, but the increase in protein content with age is reduced to about half the normal value at the end of the treatment. The treatment with 6-OHDA also results in a drastic lowering of DBH specific and total activities, and a much smaller rate of increase of COX specific and total activities with age in IBAT compared with controls. These results provide additional evidence for a previously proposed role of sympathetic nervous system activity in the development of the thermogenic potential of IBAT in the newborn rat.

1982 ◽  
Vol 60 (5) ◽  
pp. 530-537 ◽  
Author(s):  
Joan Triandafillou ◽  
Cynthia Gwilliam ◽  
Jean Himms-Hagen

The role of thyroid gland in cold-induced growth of brown adipose tissue and in cold-induced adaptive changes in brown adipose tissue mitochondria was investigated. Interscapular brown adipose tissue of thyroidectomized rats maintained at 28 °C was of normal size (protein, cytochrome oxidase content) and its mitochondria were normal, as judged from the level of GDP binding and the polypeptide composition. (GDP binds to a 32 000 dalton polypeptide component of the inner mitochondrial membrane. This component is part of the thermogenic proton conductance pathway. The level of GDP binding is a sensitive indicator of the thermogenic state of the tissue.) Brown adipose tissue mitochondria of thyroidectomized rats exposed to 4 °C for 15 h did not show the usual increase in GDP binding, an indication of a lack of a thermogenic response; the response was restored in thyroxine-treated thyroidectomized animals. In thyroidectomized rats treated with a low maintenance dose of thyroxine (25 μg/kg, s.c., three times per week) and acclimated to cold (4 °C) for 2 weeks, a normal growth of brown adipose (increase in protein and cytochrome oxidase) and normal changes in mitochondria (increase in GDP binding and an increase in the proportion of polypeptides of molecular weight 31 200 – 34 400) occurred. Treatment of intact rats with a large dose of thyroxine (1000 μg/kg, s. c., per day) resulted in a large increase in wet weight, mainly due to lipid accumulation since only small increases in protein and cytochrome oxidase and no change in DNA content occurred; mitochondrial GDP binding was decreased and polypeptide composition unchanged. It is concluded that thyroid hormone exerts a permissive effect on the cold-induced, noradrenaline-mediated, unmasking of GDP-binding sites in brown adipose tissue. The failure of the thyroidectomized rat to survive at 4 °C is probably primarily due to its inability to activate thermogenesis in its brown adipose tissue. Thyroid hormone does not appear to be involved, other than in a permissive way, in long-term cold-induced growth and mitochondrial changes in brown adipose tissue, since these occur normally in the presence of only small amounts of thyroxine in thyroidectomized rats and do not occur in intact rats treated with large amounts of thyroxine.


1980 ◽  
Vol 239 (1) ◽  
pp. C18-C22 ◽  
Author(s):  
J. Himms-Hagen ◽  
C. Gwilliam

The size (wet weight, total protein, total cytochrome oxidase) of interscapular brown adipose tissue is reduced to about one-half of normal in the cardiomyopathic hamster (BIO 14.6). The mitochondria are normal in binding of purine nucleotides [guanosine 5'-diphosphate (GDP)] and in proportion of polypeptides in the region of 32,000, both indices of the thermogenic proton conductance pathway, and in specific activity of cytochrome oxidase. Brown adipose tissue of the cardiomyopathic hamster can grow during acclimation to 4 degrees C, but its size remains smaller than in cold-acclimated normal hamsters. Mitochondrial polypeptide composition is not altered by acclimation to cold, but a large increase in mitochondrial GDP binding occurs in both normal and cardiomyopathic hamsters. The reduced calorigenic response of cardiomyopathic hamsters to catecholamines (Horwitz, B.A., and G.E. Hanes, Proc. Soc. Exp. Biol. Med. 147: 393-395, 1974) may, at least in part, be explained by a reduction in the amount of brown adipose tissue, the major site of this response. A defect in control of growth of this tissue in the cardiomyopathic hamster is suggested.


1977 ◽  
Vol 55 (2) ◽  
pp. 272-278 ◽  
Author(s):  
Josef P. Skala ◽  
Peter Hahn

A single-dose administration of 6-hydroxydopamine (50 mg/kg body weight, sc) to infant rats resulted in an enlargement, higher fresh weight, markedly elevated lipid content, and higher total protein content of their interscapular and cervical brown adipose tissue. The protein kinase (EC 2.7.1.37) activation ratio in the tissue was decreased as was the phosphoenolpyruvate carboxykinase (EC 4.1.1.32) activity. Fatty acid synthetase, on the other hand, showed an increased activity. These changes commenced as soon as 24 h after the administration of the drug, were fully developed 2–4 days later, and persisted for at least 14 days. The results are in line with the assumption that 6-hydroxydopamine administration causes chemical sympathectomy of brown adipose tissue. This is further supported by the fact that treatment with α-methyltyrosine, which is known to competitively inhibit norepinephrine synthesis, results in similar changes in brown fat of infant rats. Hence it seems that 6-hydroxydopamine administration offers a simple and inexpensive experimental model for studies of the role of the norepinephrine-mediated sympathetic nervous system in brown adipose tissue function and development.


1987 ◽  
Vol 252 (1) ◽  
pp. R160-R165 ◽  
Author(s):  
C. J. Billington ◽  
T. J. Bartness ◽  
J. Briggs ◽  
A. S. Levine ◽  
J. E. Morley

Despite long-standing observations of a whole-body thermogenic effect of glucagon, the role of glucagon in activating thermogenesis in brown adipose tissue has not often been studied. We investigated the ability of administered glucagon to produce alterations in brown adipose tissue similar to changes produced by accepted stimuli of brown fat activity: cold, norepinephrine, and overfeeding. Eighteen days of glucagon injections (1 mg/kg) to male Sprague-Dawley rats produced, relative to saline-injected controls, decreases in feed efficiency and increases in brown adipose tissue weight, protein content, DNA content, and mitochondrial mass as reflected in cytochrome oxidase activity. The observed changes were similar, though of lesser magnitude, to changes produced in these same parameters induced by administration of norepinephrine (250 micrograms/kg) for a positive control group. Four days of glucagon administration (1 mg/kg) produced increases in specific activity of cytochrome oxidase and lipoprotein lipase. After 8 days of glucagon administration, changes in whole-pad activity similar to those seen with 18 days of administration were present. Glucagon also increased whole-pad lipoprotein lipase activity after 4 and 8 days. Surgically denervated interscapular brown adipose tissue retained its ability to respond to exogenous glucagon, though the magnitude of the response was diminished. Guanosine 5'-diphosphate (GDP) binding to brown adipose tissue mitochondria was measured as an assessment of functional state after 5 days of glucagon (1 mg/kg). There was an increase in GDP binding relative to controls whether expressed as picomoles per milligram mitochondrial protein or nanomoles per pad.(ABSTRACT TRUNCATED AT 250 WORDS)


1984 ◽  
Vol 62 (10) ◽  
pp. 1327-1332 ◽  
Author(s):  
Florent Depocas ◽  
David O. Foster ◽  
Gloria Zaror-Behrens ◽  
Suzanne Lacelle ◽  
B. Nadeau

Twenty-four hours after subcutaneous administration of 6-hydroxydopamine (6-OHDA) at a dose of 10 mg/kg body weight in warm-acclimated rats, noradrenaline (NA) content and dopamine β-hydroxylase (DBH) activity of interscapular brown adipose tissue (IBAT) were reduced to about 10 and 35% of control values. Corresponding values for cold-acclimated rats, similarly treated, were 12 and 32%. In both groups of animals, calorigenic function in IBAT assessed by measurement of the effect of cold exposure on rate of blood flow through the tissue was lost almost completely. Twenty-four hours after treatment of rats with various doses of 6-OHDA, calorigenesis in IBAT was directly related to residual NA. Measurements of noradrenaline content and DBH activity from 1 to 10 days after 6-OHDA and the increase in IBAT blood flow of cold-exposed animals from 1 to 7 days after 6-OHDA indicated marked differences in the extent to which each of these indicators of the integrity and function of sympathetic nerve endings recovered with time and with the acclimation temperature of the animals. Regeneration of macromolecuiar components of noradrenergic vesicles in IBAT appeared to occur more rapidly in cold than in warm-acclimated animals. Thus, moderate doses of 6-OHDA may acutely sympathectomize IBAT, but as previously reported for other tissues, full recovery of function of IBAT occurs long before noradrenaline stores are replenished.


1991 ◽  
Vol 69 (12) ◽  
pp. 1896-1900 ◽  
Author(s):  
Anette Meywirth ◽  
Uwe Redlin ◽  
Stephan Steinlechner ◽  
Gerhard Heldmaier ◽  
Russel J. Reiter

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 °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.Key words: nonshivering thermogenesis, brown fat, 5′-deiodinase, Phodopus sungorus.


1974 ◽  
Vol 52 (6) ◽  
pp. 1051-1062 ◽  
Author(s):  
David O. Foster

The calorigenic response to infused noradrenaline (NA) of barbital-anesthetized, cold-acclimated, adult, gnotobiotic, albino rats tested 1 h after removal of interscapular brown adipose tissue (I.B.A.T.) was 14% lower than before surgery and 15% lower than the response of either sham-operated or non-operated rats; but 4 days later, the response of rats without I.B.A.T. was not significantly different from that of the controls. In unanesthetized rats, response to NA was also unaffected by interruption of blood flow to I.B.A.T. 1–3 days before the measurements. Since these results do not conform with previous findings of 30–60% reductions in response to NA following removal of I.B.A.T. or interference with the tissue's vascular connections, they contradict the current hypothesis that the B.A.T. of cold-acclimated rodents has a unique role as a mediator of calorigenesis in other tissues.A supplementary feature of the study was the discovery of apparent thermolability in the process by which cold-acclimated rats respond calorigenically to NA. If, during infusion of NA, colonic temperature exceeded about 41.5 °C, an apparently critical degree of hyperthermia response to the hormone during a subsequent infusion was reduced. This reduction was linearly related to the previous maximum colonic temperature over the range 41.6–42.4 °C and amounted to approximately 70% at 42.4 °C. These results indicate the necessity for monitoring the body temperatures of animals during infusion of NA, particularly in experiments in which two or more tests of response to NA are done on the same animal. Since such temperature measurements were not reported in those studies that have suggested a mediatory role of B.A.T. in calorigenesis in rodents, it is not possible to resolve the discrepancies on this basis.


1988 ◽  
Vol 254 (1) ◽  
pp. R11-R16 ◽  
Author(s):  
P. Trayhurn ◽  
G. Jennings

The effects of fasting and refeeding on nonshivering thermogenesis and the properties of brown adipose tissue have been investigated in mice. Fasting for 48 h led to a substantial reduction in the capacity for nonshivering thermogenesis, and there was no recovery of thermogenic capacity during the first 5 days of refeeding. A period of 10-15 days of refeeding was required for full restoration of thermogenic capacity. The mice were hyperphagic during the first 6 days of refeeding, but body weight was recovered after 24 h. The amount of interscapular brown adipose tissue decreased substantially on fasting, but it recovered 24 h after the initiation of refeeding. Cytochrome oxidase activity, the level of mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein in brown adipose tissue were each reduced by fasting. Although both GDP binding and the specific concentration of uncoupling protein rapidly returned to normal on refeeding, the activity of cytochrome oxidase was not normalized until 10 days after the end of the fast. These results indicate that a prolonged period of refeeding is required for the recovery in the capacity for nonshivering thermogenesis following a fast, a similar time course being evident for the recovery of cytochrome oxidase activity in brown adipose tissue. It is suggested that the fasting-induced reduction in the capacity for nonshivering thermogenesis is linked primarily to a loss of mitochondria from brown adipose tissue and that the normalization of thermogenic capacity is dependent on the restoration of mitochondrial mass.


2007 ◽  
Vol 32 (5) ◽  
pp. 261-269 ◽  
Author(s):  
Biljana Buzadžić ◽  
Aleksandra Korać ◽  
Vesna Petrović ◽  
Ana Vasilijević ◽  
Aleksandra Janković ◽  
...  

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