Effect of 6-hydroxydopamine and α-methyltyrosine on brown adipose tissue of infant rats

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.

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.


1990 ◽  
Vol 259 (1) ◽  
pp. R90-R96 ◽  
Author(s):  
R. Bertin ◽  
I. Mouroux ◽  
F. De Marco ◽  
R. Portet

Brown adipose tissue (BAT) has an important role in the thermogenesis of newborn mammals and cold-acclimated rodents. Heat production within the tissue is regulated by the sympathetic nervous system (SNS) via norepinephrine (NE) release. As only little is known of the progressive role of SNS during the developmental period, NE content and turnover were determined in BAT of infant rats 1-33 days of age. The dams and the pups were kept at either 28 or 16 degrees C. It was observed that the NE level in the tissue and the mediator turnover had an almost parallel evolution during the experimental period. In the first week of life, level and turnover of NE were higher in the 28 degrees C group than in the 16 degrees C group. During the second week, the level remained constant in rats kept at 28 degrees C, but the NE turnover slightly decreased. In contrast, a large increase of both parameters was observed in rats kept at 16 degrees C. Then a decrease occurred in both groups until weaning. Subsequently the values remained almost constant. It must be noted that, from the end of the first week, NE content and turnover were always significantly higher in the 16 degrees C group than in the 28 degrees C group. At the end of the first month, the level was 50% higher in cold-acclimated rats and turnover was four times as high as in controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 142-OR
Author(s):  
MASAJI SAKAGUCHI ◽  
SHOTA OKAGAWA ◽  
SAYAKA KITANO ◽  
TATSUYA KONDO ◽  
EIICHI ARAKI

Author(s):  
Aleix Gavaldà-Navarro ◽  
Joan Villarroya ◽  
Rubén Cereijo ◽  
Marta Giralt ◽  
Francesc Villarroya

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1122
Author(s):  
Jamie I. van der van der Vaart ◽  
Mariëtte R. Boon ◽  
Riekelt H. Houtkooper

Obesity is becoming a pandemic, and its prevalence is still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as a possible target to achieve this for its functional role in energy expenditure by means of increasing thermogenesis. An important metabolic sensor and regulator of whole-body energy balance is AMP-activated protein kinase (AMPK), and its role in energy metabolism is evident. This review highlights the mechanisms of BAT activation and investigates how AMPK can be used as a target for BAT activation. We review compounds and other factors that are able to activate AMPK and further discuss the therapeutic use of AMPK in BAT activation. Extensive research shows that AMPK can be activated by a number of different kinases, such as LKB1, CaMKK, but also small molecules, hormones, and metabolic stresses. AMPK is able to activate BAT by inducing adipogenesis, maintaining mitochondrial homeostasis and inducing browning in white adipose tissue. We conclude that, despite encouraging results, many uncertainties should be clarified before AMPK can be posed as a target for anti-obesity treatment via BAT activation.


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