scholarly journals Pyruvate dehydrogenase-complex activity in brown adipose tissue of gold thioglucose-obese mice

1990 ◽  
Vol 270 (1) ◽  
pp. 257-259 ◽  
Author(s):  
G J Cooney ◽  
G S Denyer ◽  
A L Kerbey ◽  
R L Frankland ◽  
S C Blair ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Kinase Activity ◽  
Pyruvate Dehydrogenase Complex ◽  
Insulin Injection ◽  
Obese Mice ◽  
Complex Activity ◽  
Gold Thioglucose ◽  
Brown Adipose

The activity of pyruvate dehydrogenase (PDH) complex and PDH kinase were measured in brown adipose tissue (BAT) of 4-week-gold thioglucose (GTG)-obese mice. The proportion of PDH complex in the active dephosphorylated form was 2-fold higher in BAT of post-absorptive obese mice compared with lean controls. This result was consistent with the higher circulating insulin concentration observed in GTG-obese mice. In both obese and lean mice the PDH-complex activity in BAT decreased after 24 h starvation and increased in response to supraphysiological insulin injection, indicating that the PDH complex is insulin-responsive in BAT of GTG-obese mice. There was no difference in the PDH kinase activity of BAT in post-absorptive or insulin-injected lean and obese mice, suggesting that the higher PDH-complex activity in obese mice was not due to decreased PDH kinase activity. There is no evidence for a decreased activity of PDH complex contributing to insulin resistance in BAT of 4-week-GTG-obese mice.

scholarly journals Tissue differences in the response of the pyruvate dehydrogenase complex to a glucose load during the development of obesity in gold-thioglucose-obese mice

1995 ◽  
Vol 305 (3) ◽  
pp. 811-816 ◽  
Author(s):  
J M Bryson ◽  
G J Cooney ◽  
V R Wensley ◽  
J L Phuyal ◽  
I D Caterson
Keyword(s):  
Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Quadriceps Muscle ◽  
Oral Glucose ◽  
Obese Mice ◽  
Glucose Load ◽  
Gold Thioglucose ◽  
Brown Adipose ◽  
Different Tissues

The activity of pyruvate dehydrogenase (PDHC), a key enzyme complex in the oxidative disposal of glucose, was measured after an oral glucose load in the heart, liver, quadriceps muscle, white adipose tissue (WAT) and brown adipose tissue (BAT) of gold-thioglucose (GTG)-obese mice at different stages during the development of obesity and in age-matched controls. Significant responses to the glucose load were seen 30 min post-gavage in heart, WAT and BAT of control mice but no change was observed in quadriceps muscle. The increase in activity of the active form of PDHC (PDHCa) in response to glucose in heart was reduced 2 weeks after the induction of GTG-obesity with no response in 5 or 10 week obese mice. A 2-3-fold increase in the PDHCa response in both WAT and BAT of 2 week obese mice was absent in 5 and 10 week obese animals. Basal PDHCa activity in quadriceps muscle was increased in 2 week obese mice but subsequently returned to control levels as obesity progressed. The glucose load produced no change in the activity of PDHCa in quadriceps muscle of obese mice. These results demonstrate that changes in the capacity for oxidative glucose disposal in different tissues, as indicated by changes in PDHCa activity, may contribute to glucose-intolerance and insulin-resistance in GTG-obese mice and that the response of the PDHC to insulin during the development of obesity varies in different tissues.

scholarly journals Changes in the lipogenic response to feeding of liver, white adipose tissue and brown adipose tissue during the development of obesity in the gold-thioglucose-injected mouse

1989 ◽  
Vol 259 (3) ◽  
pp. 651-657 ◽  
Author(s):  
G J Cooney ◽  
M A Vanner ◽  
J L Nicks ◽  
P F Williams ◽  
I D Caterson
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Liver Lipid ◽  
Insulin Concentration ◽  
Obese Mice ◽  
Interscapular Brown Adipose Tissue ◽  
Gold Thioglucose ◽  
Brown Adipose

Lipogenic response to feeding was measured in vivo in liver, epididymal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), during the development of obesity in gold-thioglucose (GTG)-injected mice. The fatty acid synthesis after a meal was higher in all tissues of GTG-treated mice on a total-tissue basis, but the magnitude of this increase varied, depending on the tissue and the time after the initiation of obesity. Lipogenesis in BAT from GTG mice was double that of control mice for the first 2 weeks, but subsequently decreased to near control values. In WAT, lipogenesis after feeding was highest 2-4 weeks after GTG injection, and in liver, lipid synthesis in fed obese mice was greatest at 7-12 weeks after the induction of obesity. The post-prandial insulin concentration was increased after 2 weeks of obesity, and serum glucose concentration was higher in fed obese mice after 4 weeks. These results indicate that increased lipogenesis in GTG-injected mice may be due to an increase in insulin concentration after feeding and that insulin resistance (assessed by lipogenic response to insulin release) is apparent in BAT before WAT and liver.

Brown adipose tissue in lean and obese mice. Insulin-receptor binding and tyrosine kinase activity

Diabetes ◽  
1986 ◽  
Vol 35 (11) ◽  
pp. 1243-1248 ◽  
Author(s):  
J. F. Tanti ◽  
T. Gremeaux ◽  
D. Brandenburg ◽  
E. Van Obberghen ◽  
Y. Le Marchand-Brustel
Keyword(s):  
Adipose Tissue ◽  
Tyrosine Kinase ◽  
Brown Adipose Tissue ◽  
Insulin Receptor ◽  
Receptor Binding ◽  
Kinase Activity ◽  
Obese Mice ◽  
Tyrosine Kinase Activity ◽  
Insulin Receptor Binding ◽  
Brown Adipose

Attenuated response to cold of brown adipose tissue of mice made obese with gold thioglucose

1989 ◽  
Vol 67 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Judy Eley ◽  
Jean Himms-Hagen
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Sympathetic Nervous System ◽  
Brown Adipose Tissue ◽  
Obese Mice ◽  
Guanosine Diphosphate ◽  
Gold Thioglucose ◽  
Brown Adipose ◽  
Sympathetic Nervous ◽  
High Level

In a first study, mice made obese with gold thioglucose became hypothermic when exposed to 4 °C. In a second study, lean mice and mice made obese with gold thioglucose (dynamic phase) were acclimated to 14 °C for up to 2 weeks and their brown adipose tissue was studied. The cold-induced increase in thyroxine 5′-deiodinase activity was initially slightly smaller in obese mice, but by 24 h and 2 weeks in the cold the activity of thyroxine 5′-deiodinase was the same in lean and obese mice. Unexpectedly, the elevated activity of 5′-deiodinase returned to the low level seen in warm-acclimated mice in both lean and obese mice after 2 weeks of cold acclimation. In gold thioglucose obese mice, a progressive cold-induced increase in the binding of guanosine diphosphate to isolated mitochondria, an index of both acute thermogenic activation and a long-term increase in uncoupling protein concentration, paralleled that seen in normal lean mice and remained at a high level after 2 weeks in the cold, although still remaining slightly lower than normal. It is not clear how a high level of mitochondrial GDP binding is maintained in cold-acclimated mice at the same time as a low level of thyroxine 5′-deiodinase activity when both are believed to be controlled by the sympathetic nervous system. We conclude that the gold thioglucose obese mouse can activate its brown adipose tissue fairly normally when it is exposed to cold, but that some attenuation of this process may contribute to the impaired survival of this mouse at low temperatures.Key words: hypothalamus, thyroxine 5′-deiodinase, guanosine diphosphate binding, sympathetic nervous system, thermoregulation.

scholarly journals Diurnal patterns of cardiac and hepatic pyruvate dehydrogenase complex activity in gold-thioglucose-obese mice

1993 ◽  
Vol 295 (3) ◽  
pp. 731-734 ◽  
Author(s):  
J M Bryson ◽  
G J Cooney ◽  
V R Wensley ◽  
S C Blair ◽  
I D Caterson
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Serum Insulin ◽  
Pyruvate Dehydrogenase Complex ◽  
Fold Increase ◽  
Hepatic Lipogenesis ◽  
Obese Mice ◽  
Diurnal Pattern ◽  
Complex Activity ◽  
Gold Thioglucose ◽  
Dehydrogenase Complex

The diurnal pattern of the activity of the pyruvate dehydrogenase complex (PDHC) was studied in the heart and liver of gold-thioglucose (GTG)-obese mice and age-matched controls. The diurnal pattern of lipogenesis was also measured in the liver. Both lean and obese mice had one main eating period, from 20:00 to 24:00 h. Eating produced no change in serum glucose of control mice but there was a significant rise in serum insulin and triacylglycerols. There was also a 3-fold increase in cardiac PDHC activity and a 3-fold increase in hepatic lipogenesis in the control mice, but little change in hepatic PDHC activity. GTG-obese mice were hyperglycaemic, hyperinsulinaemic and hypertriglyceridaemic at all times studied, with significant increases in these parameters being seen in response to eating. Eating produced little change in cardiac PDHC activity, but there was a 5-fold increase in hepatic PDHC activity, paralleled by a 10-fold increase in hepatic lipogenesis. Hepatic PDHC activity was significantly higher in GTG-obese mice at all times except 16:00 h. The simultaneous rise of hepatic PDHC activity, lipogenesis and serum triacylglycerols in GTG-obese mice suggests an increased utilization of glucose for lipogenesis. The lack of change in heart PDHC activity in GTG-obese mice over 24 h suggests that a general decrease in PDHC activity may contribute to the development of the glucose intolerance and insulin resistance of obesity and non-insulin-dependent diabetes. However, it appears that a different level of metabolic control allows hepatic PDHC activity of the same obese animals to increase in response to hyperinsulinaemia and contribute to the higher rates of lipogenesis seen in obese mice.

scholarly journals Pyruvate dehydrogenase activities and rates of lipogenesis during the fed-to-starved transition in liver and brown adipose tissue of the rat

1990 ◽  
Vol 268 (1) ◽  
pp. 77-81 ◽  
Author(s):  
M J Holness ◽  
M C Sugden
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Insulin Treatment ◽  
Pyruvate Dehydrogenase Complex ◽  
Active Form ◽  
Lipid Synthesis ◽  
Brown Fat ◽  
Fed State ◽  
Brown Adipose

The percentages of pyruvate dehydrogenase complex (PDH) in the active form (PDHa) in two lipogenic tissues (liver and brown adipose tissue) in the fed state were 12.0% and 13.4% respectively. After acute (0.5 h) insulin treatment, PDHa activities had increased by 77% in liver and by 234% in brown fat. Significant decreases in PDHa activities were observed in both tissues by 5 h after the removal of food. The patterns of decline in PDHa activities in the two lipogenic tissues were similar in that the major decreases in activities were observed within the first 7 h of starvation. The significant decreases in PDHa activities observed after starvation for 6 h were accompanied by decreased rates of lipogenesis. Hepatic and brown-fat PDHa activities after acute (30 min) exposure to exogenous insulin were less in 6 h-starved than in fed rats, but the absolute increases in PDHa activities over the 30 min exposure period were similar in fed and 6 h-starved rats. Increases in PDHa activities were paralleled by increases in lipid synthesis in both tissues. Re-activation of PDH in response to insulin treatment or chow re-feeding after 48 h starvation occurred more rapidly in brown adipose tissue than in liver. The results are discussed in relation to the importance of the activity of the PDH complex as a determinant of the total rate of lipogenesis during the fed-to-starved transition and after insulin challenge or re-feeding.

Brown adipose tissue of mice with gold thioglucose-induced obesity: effect of cold and diet

1983 ◽  
Vol 244 (6) ◽  
pp. E581-E588 ◽  
Author(s):  
S. Hogan ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Acclimation ◽  
Obese Mouse ◽  
Metabolic Efficiency ◽  
Obese Mice ◽  
Gold Thioglucose ◽  
Bat Mitochondria ◽  
Brown Adipose ◽  
Diet Induced Thermogenesis

Gold thioglucose (GTG)-obese mice have a larger than normal amount of brown adipose tissue (BAT) with ultrastructurally normal mitochondria. The tissue grows normally when the mice adapt to cafeteria feeding or to cold (8 degrees C). Acute exposure to cold causes a fairly normal thermogenic activation of BAT mitochondria of GTG-obese mice, both in dynamic and static phases of their obesity. However, chow-fed GTG-obese mice have BAT mitochondria that are in a low state of thermogenic activation, and these mice fail to respond to eating a cafeteria diet for 3 wk by a normal thermogenic activation of their BAT mitochondria. More prolonged cafeteria feeding for 11-13 wk, into the static phase of obesity, is associated with thermogenic activation of BAT mitochondria of GTG-obese mice. The capacity of GTG-obese mice to respond to noradrenaline (norepinephrine) by an increase in metabolic rate is greater than that of lean mice and is further enhanced by cold acclimation. It is concluded that BAT of the GTG-obese mouse is inherently functional, as is control of its thermogenic function and growth during cold exposure and cold acclimation. Dietary influences on BAT thermogenic function are, however, defective in the GTG-obese mouse at least during the dynamic phase of its obesity. The resulting failure of diet-induced thermogenesis would be expected to contribute to the known high metabolic efficiency of the GTG-obese mouse and, together with the hyperphagia, to the obesity induced by GTG.

Brown Adipose Tissue in Lean and Obese Mice: Insulin-Receptor Binding and Tyrosine Kinase Activity

Diabetes ◽  
1986 ◽  
Vol 35 (11) ◽  
pp. 1243-1248 ◽  
Author(s):  
J. -F. Tanti ◽  
T. Gremeaux ◽  
D. Brandenburg ◽  
E. V. Obberghen ◽  
Y. L. Marchand-Brustel
Keyword(s):  
Adipose Tissue ◽  
Tyrosine Kinase ◽  
Brown Adipose Tissue ◽  
Insulin Receptor ◽  
Receptor Binding ◽  
Kinase Activity ◽  
Obese Mice ◽  
Tyrosine Kinase Activity ◽  
Insulin Receptor Binding ◽  
Brown Adipose

Effect of a thermogenic agent, BRL 26830A, on insulin receptors in obese mice

1988 ◽  
Vol 255 (2) ◽  
pp. E101-E109 ◽  
Author(s):  
N. Rochet ◽  
J. F. Tanti ◽  
T. Gremeaux ◽  
E. Van Obberghen ◽  
Y. Le Marchand-Brustel
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Insulin Receptor ◽  
Kinase Activity ◽  
Insulin Receptors ◽  
Receptor Kinase ◽  
Obese Mice ◽  
Brown Adipose ◽  
Receptor Number

The effect of a new type of antidiabetic agent, BRL 26830A, has been tested in obese mice. Since this drug increases thermogenesis, insulin receptor binding and kinase activity were studied in brown adipose tissue and skeletal muscle of mice made obese by gold thioglucose. At 1 mg.kg-1.day-1, a 3-wk treatment normalized the glycemia and increased the uncoupling protein content of brown adipose tissue. The insulin receptor number and its associated kinase activity increased only in brown adipose tissue. At 2 mg.kg-1.day-1, additional effects, i.e., a 20% reduction in body weight and a normalization of insulin receptor number both in brown adipose tissue and in skeletal muscle, were observed. All those results were obtained even though hyperinsulinemia was not corrected. At the higher drug dosage, insulin receptor kinase activity evolved in direct proportion to the receptor number in brown adipose tissue. By contrast, in skeletal muscle, the receptor kinase activity toward exogenous substrates increased more than the receptor number, suggesting that the alteration of insulin receptor kinase activity previously reported in skeletal muscle of obese mice was partly reversed by BRL 26830A. None of these parameters was modified by the drug in lean mice. These results show that, even without affecting obesity, BRL 26830A improves insulin resistance in obese mice, probably through its effect on insulin receptors. This action prevails in brown adipose tissue, supporting the idea that this tissue plays an important role in glucose homeostasis. Thermogenic drugs could thus be powerful agents for the treatment of noninsulin-dependent diabetics.

142-OR: Unique Role of the a4 Component for S6-Kinase Activity in Metabolic Regulation and Anti-apoptotic Effect in Brown Adipose Tissue

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 142-OR
Author(s):  
MASAJI SAKAGUCHI ◽  
SHOTA OKAGAWA ◽  
SAYAKA KITANO ◽  
TATSUYA KONDO ◽  
EIICHI ARAKI
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Metabolic Regulation ◽  
Kinase Activity ◽  
S6 Kinase ◽  
Unique Role ◽  
Brown Adipose ◽  
Apoptotic Effect
Sign in / Sign up

Export Citation Format

Share Document