Glucocorticoid deprivation alters in vivo glucose uptake by muscle and adipose tissues of GTG-obese mice

1995 ◽  
Vol 269 (5) ◽  
pp. E927-E933
Author(s):  
S. C. Blair ◽  
I. D. Caterson ◽  
G. J. Cooney
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Quadriceps Muscle ◽  
Obese Mice ◽  
Interscapular Brown Adipose Tissue ◽  
Gold Thioglucose ◽  
Brown Adipose

The effect of 1 wk of glucocorticoid deprivation by surgical adrenalectomy (ADX) on tissue 2-deoxy(-)[U-14C]glucose (2-DG) uptake and hepatic glucose production (HGP) was assessed in conscious, catheterized mice 5 wk after the induction of obesity with gold thioglucose (GTG). Despite the prevailing hyperglycemia and hyperinsulinemia, glucose uptake by heart, quadriceps muscle, and interscapular brown adipose tissue (BAT) of GTG-obese mice was unchanged compared with controls, suggesting that the hyperglycemia of GTG-obese mice is able to compensate for the insulin resistance of these tissues. In contrast, epididymal white adipose tissue (WAT) of GTG-obese mice showed increased glucose uptake with hyperglycemia and hyperinsulinemia. ADX decreased the hyperglycemia and lowered the elevated glycogen content of the liver of GTG-obese mice. ADX reduced glucose uptake by heart and WAT of control and GTG-obese mice, consistent with the concomitant decrease in insulinemia. Glucose uptake by muscle of control and GTG-obese mice was not significantly decreased after ADX despite the decrease in insulin, and ADX increased glucose uptake by BAT of GTG-obese mice, suggesting increased sympathetically mediated thermogenesis in this tissue. HGP was increased in GTG-obese mice compared with controls, and ADX significantly reduced HGP in both GTG-obese and control mice. These results suggest that the improved glucose tolerance of ADX GTG-obese mice and ADX control mice is due to a decrease in HGP rather than an increase in peripheral glucose uptake.

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.

Effect of adrenalectomy on glucose tolerance and lipid metabolism in gold-thioglucose obese mice

1994 ◽  
Vol 266 (6) ◽  
pp. E993-E1000 ◽  
Author(s):  
S. C. Blair ◽  
I. D. Caterson ◽  
G. J. Cooney
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Fatty Acid Content ◽  
Fasting Blood Glucose ◽  
Lipid Synthesis ◽  
Obese Mice ◽  
Interscapular Brown Adipose Tissue ◽  
Gold Thioglucose ◽  
Brown Adipose

The effect of adrenalectomy (ADX) on body weight, lipogenesis, and glucose tolerance was investigated in mice made obese by a single intraperitoneal injection of gold-thioglucose (GTG). Five weeks after ADX the weight of GTG-obese mice was significantly decreased (GTG-obese+sham-ADX: 39.8 +/- 0.8 g; GTG-obese+ADX: 27.6 +/- 1.1 g; P < 0.05). ADX also reduced serum glucose (GTG-obese+sham-ADX: 16.5 +/- 0.6 mmol/l; GTG-obese+ADX: 10.8 +/- 0.5 mmol/l; P < 0.05) and serum insulin concentrations (GTG-obese+sham-ADX: 197 +/- 36 microU/ml; GTG-obese+ADX: 38 +/- 7 microU/ml; P < 0.05) of fed GTG-obese mice and greatly improved glucose tolerance. ADX lowered liver glycogen content and reduced the fatty acid content of liver, epididymal white adipose tissue (WAT), and interscapular brown adipose tissue (BAT) of fed GTG-obese mice. Lipid synthesis in liver and WAT of GTG-obese mice was decreased by ADX, but lipogenesis in BAT was increased, possibly to provide substrate for increased thermogenesis in this tissue. Effects of ADX on metabolism were not confined to GTG-injected mice, as ADX also reduced body weight and altered the glucose tolerance of age-matched control mice. ADX increased lipid synthesis in liver, WAT, and BAT of fed control mice without an increase in lipid deposition, indicating that there was increased lipid turnover in these lipogenic tissues of ADX mice. ADX reduced the fasting blood glucose concentration of both control and GTG-obese mice to a level below that of sham-ADX control mice (sham-ADX control: 6.0 +/- 0.4 mM; ADX control: 2.9 +/- 0.5 mM; ADX GTG-obese: 3.3 +/- 0.2 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Developmental changes in fatty acid synthesis in interscapular brown adipose tissue of lean and genetically obese (ob/ob) mice

1983 ◽  
Vol 212 (2) ◽  
pp. 393-398 ◽  
Author(s):  
S W Mercer ◽  
P Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Obese Mice ◽  
Carbohydrate Diet ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

Fatty acid synthesis was measured in vivo with 3H2O in interscapular brown adipose tissue of lean and genetically obese (ob/ob) mice. At 26 days of age, before the development of hyperphagia, synthesis in brown adipose tissue was higher in the obese than in the lean mice; synthesis was also elevated in the liver, white adipose tissue and carcass of the obese mice. At 8 weeks of age, when hyperphagia was well established, synthesis remained elevated in all tissues of the obese mice, with the exception of brown adipose tissue. Elevated synthesis rates were not apparent in brown adipose tissue of the obese mice at 14 days of age, nor at 35 days of age. These results demonstrate that brown adipose tissue in ob/ob mice has a transitory hyperlipogenesis at, and just after, weaning on to a low-fat/high-carbohydrate diet. Once hyperphagia has developed, by week 5 of life, brown adipose tissue is the only major lipogenic tissue in the obese mice not to exhibit elevated rates of fatty acid synthesis; this suggests that insulin resistance develops much more rapidly in brown adipose tissue than in other lipogenic tissues of the ob/ob mouse.

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 RalA controls glucose homeostasis by regulating glucose uptake in brown fat

2018 ◽  
Vol 115 (30) ◽  
pp. 7819-7824 ◽  
Author(s):  
Yuliya Skorobogatko ◽  
Morgan Dragan ◽  
Claudia Cordon ◽  
Shannon M. Reilly ◽  
Chao-Wei Hung ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Brown Fat ◽  
Specific Chemical ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Chemical Inhibitors ◽  
Glucose Transporter Glut4

Insulin increases glucose uptake into adipose tissue and muscle by increasing trafficking of the glucose transporter Glut4. In cultured adipocytes, the exocytosis of Glut4 relies on activation of the small G protein RalA by insulin, via inhibition of its GTPase activating complex RalGAP. Here, we evaluate the role of RalA in glucose uptake in vivo with specific chemical inhibitors and by generation of mice with adipocyte-specific knockout of RalGAPB. RalA was profoundly activated in brown adipose tissue after feeding, and its inhibition prevented Glut4 exocytosis. RalGAPB knockout mice with diet-induced obesity were protected from the development of metabolic disease due to increased glucose uptake into brown fat. Thus, RalA plays a crucial role in glucose transport in adipose tissue in vivo.

Fatty acid synthesis and generation of glycerol-3-phosphate in brown adipose tissue from rats fed a cafeteria diet

2008 ◽  
Vol 86 (7) ◽  
pp. 416-423 ◽  
Author(s):  
Valéria E. Chaves ◽  
Danúbia Frasson ◽  
Maria E.S. Martins-Santos ◽  
Luiz C.C. Navegantes ◽  
Victor D. Galban ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Content ◽  
Acid Synthesis ◽  
Cafeteria Diet ◽  
Brown Adipose

In vivo fatty acid synthesis and the pathways of glycerol-3-phosphate (G3P) production were investigated in brown adipose tissue (BAT) from rats fed a cafeteria diet for 3 weeks. In spite of BAT activation, the diet promoted an increase in the carcass fatty acid content. Plasma insulin levels were markedly increased in cafeteria diet-fed rats. Two insulin-sensitive processes, in vivo fatty acid synthesis and in vivo glucose uptake (which was used to evaluate G3P generation via glycolysis) were increased in BAT from rats fed the cafeteria diet. Direct glycerol phosphorylation, evaluated by glycerokinase (GyK) activity and incorporation of [U-14C]glycerol into triacylglycerol (TAG)–glycerol, was also markedly increased in BAT from these rats. In contrast, the cafeteria diet induced a marked reduction of BAT glyceroneogenesis, evaluated by phosphoenolpyruvate carboxykinase-C activity and incorporation of [1-14C]pyruvate into TAG–glycerol. BAT denervation resulted in an approximately 50% reduction of GyK activity, but did not significantly affect BAT in vivo fatty acid synthesis, in vivo glucose uptake, or glyceroneogenesis. The data suggest that the supply of G3P for BAT TAG synthesis can be adjusted independently from the sympathetic nervous system and solely by reciprocal changes in the generation of G3P via glycolysis and via glyceroneogenesis, with no participation of direct phosphorylation of glycerol by GyK.

scholarly journals The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine deiodination in cold-exposed, sympathectomized rat brown fat

2000 ◽  
pp. 273-277 ◽  
Author(s):  
D Hofer ◽  
M Raices ◽  
K Schauenstein ◽  
S Porta ◽  
W Korsatko ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Receptor Agonist ◽  
Wistar Rats ◽  
Type Ii ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Cgp 12177 ◽  
In Vivo Effects

OBJECTIVE: The effects of the beta-3-receptor agonist CGP-12177 on thyroxine (T4) deiodination in sympathectomized (SX) interscapular brown adipose tissue (BAT) were assessed in 300 g body weight (BW) Wistar rats. DESIGN: Seven days after SX, groups of rats were implanted s.c. with pellets containing 5mg CGP-12177 or 5mg norepinephrine (NE) and were immediately placed at 4 degrees C for 24h. Other SX groups were injected with CGP-12177 or NE 1mg/kg BW i. p. and placed in the cold for 4h. The latter group was injected, in addition, with prazosin 0.4 mg/100g BW i.p. or propranolol 0.5mg/100g BW i.p. 15 min before and 2h after the administration of CGP-12177 or NE. METHODS: Two hours after the last injection of prazosin or propranolol, animals were killed and BAT was removed, homogenized and centrifuged at 500 g for 10 min at 4 degrees C. The infranatants were incubated during 60 min in the presence of dithiothreitol and 1 microCi [(125)I]T4. Aliquots were chromatographed on paper for the measurement of [(125)I]T4 and its deiodinated subproducts. RESULTS: CGP-12177 restored normal T4 deiodination in SX BAT from both groups, but NE was slightly more effective. Propranolol, although not prazosin, blocked the CGP-12177 effects. Contrariwise, the NE-induced rise in deiodination was blocked by prazosin and to a lesser extent by propranolol. CONCLUSIONS: The results indicate that CGP-12177 stimulated the in vivo activation of 5'-deiodinase type II activity predominantly via beta-3-receptor, without participation of alpha-1-receptors.

scholarly journals A Diurnal Rhythm in Glucose Uptake in Brown Adipose Tissue Revealed by In Vivo PET-FDG Imaging

Obesity ◽  
2012 ◽  
Vol 20 (7) ◽  
pp. 1527-1529 ◽  
Author(s):  
Daan R. van der Veen ◽  
Jinping Shao ◽  
Sarah Chapman ◽  
W. Matthew Leevy ◽  
Giles E. Duffield
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
Diurnal Rhythm ◽  
Brown Adipose

Transient upregulation of IGF-I gene expression in brown adipose tissue of cold-exposed rats

1997 ◽  
Vol 272 (3) ◽  
pp. E453-E460 ◽  
Author(s):  
C. Duchamp ◽  
K. A. Burton ◽  
A. Geloen ◽  
M. J. Dauncey
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Unit Weight ◽  
Mrna Levels ◽  
Interscapular Brown Adipose Tissue ◽  
Total Rna ◽  
Brown Adipose ◽  
Igf I

The possible involvement of locally produced insulin-like growth factor I (IGF-I) in the cold-induced hyperplasia of interscapular brown adipose tissue (BAT) was investigated in 2-, 4-, and 7-day cold-exposed (CE, 4 degrees C) rats by measuring BAT IGF-I expression at a time when extensive BAT cell proliferation occurs. By comparison with thermoneutral (25 degrees C) controls, plasma IGF-I decreased in CE rats despite an increased food intake, whereas BAT IGF-I peptide increased markedly to peak after 4 days at 4 degrees C. The ratio of class 1 to class 2 IGF-I mRNA was much higher in BAT than in liver. BAT IGF-I mRNA levels per unit weight total RNA doubled after 2 days at 4 degrees C but decreased thereafter to the level in controls. Upregulation of BAT IGF-I mRNA also occurred in CE rats with a food intake restricted to the level of controls. The transient cold-induced upregulation of BAT IGF-I (per unit weight total RNA) suggests that IGF-I plays a role in the early cold-induced BAT hyperplasia that occurs in vivo.

scholarly journals Nutrient Responsive Nesfatin-1 Regulates Energy Balance and Induces Glucose-Stimulated Insulin Secretion in Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3628-3637 ◽  
Author(s):  
R. Gonzalez ◽  
R. L. S. Perry ◽  
X. Gao ◽  
M. P. Gaidhu ◽  
R. G. Tsushima ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Secretion ◽  
Glucose Uptake ◽  
Pancreatic Islets ◽  
Whole Body ◽  
Isolated Pancreatic Islets ◽  
Brown Adipose ◽  
Glucose Stimulated Insulin Secretion ◽  
Body Energy

Nesfatin-1 is a recently discovered anorexigen, and we first reported nesfatin-like immunoreactivity in the pancreatic β-cells. The aim of this study was to characterize the effects of nesfatin-1 on whole-body energy homeostasis, insulin secretion, and glycemia. The in vivo effects of continuous peripheral delivery of nesfatin-1 using osmotic minipumps on food intake and substrate partitioning were examined in ad libitum-fed male Fischer 344 rats. The effects of nesfatin-1 on glucose-stimulated insulin secretion (GSIS) were examined in isolated pancreatic islets. L6 skeletal muscle cells and isolated rat adipocytes were used to assess the effects of nesfatin-1 on basal and insulin-mediated glucose uptake as well as on major steps of insulin signaling in these cells. Nesfatin-1 reduced cumulative food intake and increased spontaneous physical activity, whole-body fat oxidation, and carnitine palmitoyltransferase I mRNA expression in brown adipose tissue but did not affect uncoupling protein 1 mRNA in the brown adipose tissue. Nesfatin-1 significantly enhanced GSIS in vivo during an oral glucose tolerance test and improved insulin sensitivity. Although insulin-stimulated glucose uptake in L6 muscle cells was inhibited by nesfatin-1 pretreatment, basal and insulin-induced glucose uptake in adipocytes from nesfatin-1-treated rats was significantly increased. In agreement with our in vivo results, nesfatin-1 enhanced GSIS from isolated pancreatic islets at both normal (5.6 mm) and high (16.7 mm), but not at low (2 mm), glucose concentrations. Furthermore, nesfatin-1/nucleobindin 2 release from rat pancreatic islets was stimulated by glucose. Collectively, our data indicate that glucose-responsive nesfatin-1 regulates insulin secretion, glucose homeostasis, and whole-body energy balance in rats.

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