Adenylate cyclase activity in brown adipose tissue of the genetically obese (ob/ob) mouse

1982 ◽  
Vol 60 (9) ◽  
pp. 910-916 ◽  
Author(s):  
Nicole Bégin-Heick ◽  
H. M. C. Heick
Keyword(s):  
Adipose Tissue ◽  
Adenylate Cyclase ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Obese Mouse ◽  
Obese Mice ◽  
Adrenergic Agonists ◽  
Brown Adipose ◽  
Maximum Activation ◽  
Obesity Syndrome

The activation of brown adipose tissue adenylate cyclase by catecholamines was studied in genetically obese (ob/ob) and lean mice. In obese mice, the maximum activation of the enzyme by several β-adrenergic agonists was only two-thirds that in lean mice and, as an activator, noradrenaline was only one-eighth as potent. The adenylate cyclase was also less responsive to guanine nucleotides. In these respects, the defect in catecholamine-stimulated adenylate cyclase was similar in both white and brown adipose tissue of the obese mouse. The enzyme in brown adipose tissue differed from that in white adipose tissue in its sensitivity to other β-adrenergic agonists and in its requirement for Mg2+. It is suggested that this abnormal catecholamine-activated adenylate cyclase in brown adipose tissue may be related to the thermoregulatory defect of the obese mouse and hence may contribute to the obesity syndrome.

Control mechanisms in brown adipose tissue plasma membrane

1984 ◽  
Vol 62 (7) ◽  
pp. 631-636 ◽  
Author(s):  
N. Bégin-Heick ◽  
H. M. C. Heick
Keyword(s):  
Adipose Tissue ◽  
Plasma Membrane ◽  
Adenylate Cyclase ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Metabolic Effects ◽  
Maximal Response ◽  
Obese Mouse ◽  
Control Mechanisms ◽  
Brown Adipose

It is generally agreed that the site of heat production during nonshivering thermogenesis is the brown adipose tissue (BAT) and that the triggering event for heat production is the interaction of noradrenaline (NA) with its receptor on the plasma membrane. Following this initial event, several changes occur which result in increased rates of cAMP synthesis, redistribution of ions across the membrane, enhanced rates of lipolysis, and increased mitochondrial oxidation of substrates. BAT is also a target for the anabolic effect of insulin. Available evidence shows that insulin receptors are present on the BAT plasma membrane and that insulin can oppose the metabolic effects of catecholamine on BAT. We have studied more particularly the response of BAT adenylate cyclase to catecholamines in an animal model (the ob/ob mouse) which has a defective thermogenic response. The capacity of adenylate cyclase to be stimulated by catecholamines was significantly less in the tissue of obese mice than in lean controls. To produce a response equal to the half-maximal response in the lean mouse, a 10-fold increase in the NA concentration was required in the BAT of the obese mouse. These results are in harmony with those of others showing that the lipolytic response to catecholamines is abnormal in the BAT of the obese mouse. The adenylate cyclase activity can be altered by changes in the lipid composition of the diet and by manipulation of hormone levels. It is likely that the alteration in adenylate cyclase responsiveness is one of the contributing factors in the impaired thermogenesis and obesity in this animal.

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 thermogenesis, torpor, and obesity of glutamate-treated mice

1986 ◽  
Vol 251 (4) ◽  
pp. E407-E415 ◽  
Author(s):  
K. Tokuyama ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Normal Male ◽  
Obese Mouse ◽  
Metabolic Efficiency ◽  
Obese Mice ◽  
Male Mice ◽  
Corticosterone Concentration ◽  
Female Mice ◽  
Brown Adipose

Mice treated with glutamate in the neonatal period are known to develop into stunted obese adults, despite hypophagia. Our objective was to find out whether brown adipose tissue (BAT) thermogenic function might be abnormal in the glutamate-obese mouse. At 10 wk of age, group-housed glutamate-obese mice exhibited nocturnal and early diurnal torpor, i.e., they thermoregulated at a lower than normal body temperature. When exposed to 4 degrees C, they died in hypothermia within 24 h. They could adapt to living at 14 degrees C for up to 1 wk but failed to adjust their food intake sufficiently to maintain their body weight. Their fat stores were, nevertheless, conserved. BAT was present in increased amounts in glutamate-obese mice. Its thermogenic activity (as assessed by the level of mitochondrial GDP binding) was normal (male mice) or reduced (female mice). A normal thermogenic responsiveness of BAT to cold occurred. The thermogenic response of BAT to a cafeteria diet was normal (male mice) or reduced (female mice). Serum corticosterone concentration was increased in both male and female glutamate-treated mice particularly in the cold. We conclude that the high metabolic efficiency and obesity of the glutamate-obese mouse are principally a consequence of its maintenance of a hypothermic torpid state for more than 50% of the time. An additional deficit in energy expenditure in female, but not male, glutamate-obese mice is associated with suppressed responsiveness of the thermogenic function of BAT to diet and may account for the greater degree of obesity in female than in male glutamate-treated mice.

Brown adipose tissue of mice with GTG-induced obesity: altered circadian control

1989 ◽  
Vol 256 (6) ◽  
pp. E773-E779 ◽  
Author(s):  
J. Eley ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Circadian Rhythm ◽  
Brown Adipose Tissue ◽  
Time Of Day ◽  
Cafeteria Diet ◽  
Obese Mouse ◽  
Restricted Feeding ◽  
Obese Mice ◽  
Brown Adipose ◽  
Stimulation Of

The effect of feeding a "cafeteria" diet and of feeding a restricted amount of chow on brown adipose tissue (BAT) of lean and gold thioglucose (GTG)-obese mice was studied at various times of the day and night. Objectives were to find out 1) whether our previous finding of diet-induced growth of BAT of the GTG-obese mouse without thermogenic activation could be explained by a transient stimulation at a time of day not studied and 2) whether lack of stimulation of BAT thyroxine 5'-deiodinase (TD) by diet seen previously in lean mice and rats could be explained by a transient increase at times of day not studied. A transient activation of BAT thermogenesis, indicated by an increase in mitochondrial GDP binding, occurs immediately after cafeteria food is presented to the GTG-obese mouse, but the effect of diet is absent at other times. This transient stimulation of BAT in the GTG-obese mouse may be sufficient to produce the tissue growth observed. A circadian rhythm in GDP binding occurred in both lean and obese mice, whether they were eating chow or the cafeteria diet. Restricted feeding suppressed BAT mitochondrial GDP binding in lean mice but did not suppress any further the low level in GTG-obese mice. A circadian rhythm in TD activity in BAT also occurred in lean and obese mice, but no effect of cafeteria diet or of restricted feeding on this enzyme was detected at any time of day, except for a brief increase in obese mice at 0500.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

scholarly journals Emodin Improves Glucose and Lipid Metabolism Disorders in Obese Mice via Activating Brown Adipose Tissue and Inducing Browning of White Adipose Tissue

2021 ◽  
Vol 12 ◽  
Author(s):  
Long Cheng ◽  
Shuofeng Zhang ◽  
Fei Shang ◽  
Yibo Ning ◽  
Zhiqi Huang ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Protein Expression ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Blood Lipids ◽  
The Body ◽  
Obese Mice ◽  
Brown Adipose

BackgroundAdipose tissue (e.g. white, brown and brite) plays a critical role in modulating energy metabolism. Activating brown adipose tissue (BAT) and inducing browning in white adipose tissue (WAT) has been proposed to be a potential molecular target for obesity treatment. Emodin is a natural anthraquinone derivative that exhibits variety of pharmacologic effects including lowering lipids and regulating glucose utilization. However, the underlying mechanism of action is still unclear. In the present study, we investigated whether emodin could alleviate obesity via promoting browning process in adipose tissue.MethodsC57BL/6J mice were fed with high fat diet to induce obesity. Emodin at the doses of 40 and 80 mg/kg were orally given to obesity mice for consecutive 6 weeks. Parameters including fasting blood glucose, oral glucose tolerance, blood lipids, and the ratios of subcutaneous white adipose tissue (scWAT) or BAT mass to body weight, and morphology of adipose tissue were observed. Besides, the protein expression of uncoupling protein 1 (UCP1) and prohibitin in BAT and scWAT was determined by immunohistochemistry method. Relative mRNA expression of Cd137, transmembrane protein 26 (Tmem26) and Tbx1 in scWAT was analyzed using qRT-PCR. And the protein expression of UCP1, CD36, fatty acid transporter 4 (FATP4), peroxisome proliferator-activated receptor alpha (PPARα) and prohibitin of scWAT and BAT were analyzed using western blotting. In addition, ultra-high-performance liquid chromatography with electrospray ionization tandem mass spectrometry was utilized to detect the small lipid metabolites of scWAT and BAT.ResultsEmodin decreased the body weight and food intake in HFD-induced obesity mice, and it also improved the glucose tolerance and reduced the blood lipids. Emodin treatment induced beiging of WAT, and more multilocular lipid droplets were found in scWAT. Also, emodin significantly increased markers of beige adipocytes, e.g. Cd137, Tmem26 and Tbx1 mRNA in scWAT, and UCP1, CD36, FATP4, PPARα and prohibitin protein expression in scWAT and BAT. Furthermore, emodin perturbed the lipidomic profiles in scWAT and BAT of obese mice. Emodin increased total ceramides (Cers), lysophosphatidylcholines (LPCs), lyso-phosphatidylcholines oxygen (LPCs-O), and phosphatidylethanolamines oxygen (PEs-O) species concentration in scWAT. Specifically, emodin significantly up-regulated levels of Cer (34:1), LPC (18:2), LPC-(O-20:2), PC (O-40:7), PE (O-36:3), PE (O-38:6), PE (O-40:6), and sphingolipid (41:0) [SM (41:0)], and down-regulated PC (O-38:0), PE (O-40:4), PE (O-40:5) in scWAT of obesity mice. In terms of lipid matabolites of BAT, the emodin remarkably increased the total PCs levels, which was driven by significant increase of PC (30:0), PC (32:1), PC (32:2), PC (33:4) and PC (38:0) species. In addition, it also increased species of LPCs, e.g. LPC (20:0), LPC (20:1), LPC (22:0), LPC (22:1), LPC (24:0), and LPC (24:1). Especially, emodin treatment could reverse the ratio of PC/PE in HFD-induced obese mice.ConclusionsThese results indicated that emodin could ameliorate adiposity and improve metabolic disorders in obese mice. Also, emodin could promote browning in scWAT and activate the BAT activities. In addition, emodin treatment-induced changes to the scWAT and BAT lipidome were highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflects selective remodeling in scWAT and BAT of both glycerophospholipids and sphingolipids in response to emodin treatment.

The effect of the divalent cations Mg2+ and Mn2+ on adenylate cyclase activity in white and brown adipose tissue of lean and obese (ob/ob) mice

1985 ◽  
Vol 63 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Nicole Bégin-Heick
Keyword(s):  
Adipose Tissue ◽  
Adenylate Cyclase ◽  
Brown Adipose Tissue ◽  
Divalent Cations ◽  
Cyclase Activity ◽  
Obese Mice ◽  
Brown Adipose ◽  
Maximal Activation ◽  
Excess Mg ◽  
Dose Dependent

The divalent cations Mg2+ and Mn2+ in excess of the concentrations required to complex with ATP (excess Mg2+ or Mn2+) modulate the activity of adenylate cyclase. As a substrate, Mn∙ATP was at least as effective as Mg∙ATP in supporting adenylate cyclase activity in white and brown adipose tissue membranes. Both excess Mg2+ and Mn2+ had quantitatively different effects on the enzyme of lean and ob/ob mice and qualitatively different effects in white and brown adipose tissue. In white adipocyte membranes excess Mg2+ increased basal activity, as well as activity owing to guanylylimidodiphosphate (Gpp(NH)p) (with or without isoproterenol) and NaF. Maximal activation by Gpp(NH)p + isoproterenol required a higher concentration of Mg2+ in tissue from ob/ob than lean mice. Excess Mn2+ prevented the activation of the enzyme by Gpp(NH)p or Gpp(NH)p + isoproterenol in a dose-dependent manner. Mn2+ inhibited even in the presence of maximally effective Mg2+ concentrations. The enzyme of the ob/ob mouse membrane required a significantly higher dose of Mn2+ to achieve 50% inhibition. In brown adipose tissue, specific activities of the isoproterenol + Gpp(NH)p and NaF stimulated enzyme were significantly lower in the obese mice under all conditions studied. Except that NaF-stimulated activity was increased significantly more in the membranes of lean mice by the combination of Mg2+ + Mn2+, these cations did not produce significantly different dose-dependent effects in membranes from lean and ob/ob mice. Maximal activation occurred at lower concentrations of MgCl2 (3–5 versus 10–20 mM) and required higher concentrations of MnCl2 (3–5 versus 1 mM) in brown than in white adipose tissue membranes. Furthermore, Mn2+ in excess of the concentration required to activate maximally produced little or no inhibitory effect on the brown adipose tissue enzyme. These studies illustrate the diversity of adenylate cyclase modulation in different tissues. Further studies with bacterial toxins will be necessary to verify whether there are differences in the equilibrium of association of the stimulatory and inhibitory components of guanine nucleotide regulatory proteins in tissues of lean and obese mice.

scholarly journals Reduced Expression of Urokinase Plasminogen Activator in Brown Adipose Tissue of Obese Mouse Models

2021 ◽  
Vol 22 (7) ◽  
pp. 3407
Author(s):  
Chung-Ze Wu ◽  
Li-Chien Chang ◽  
Chao-Wen Cheng ◽  
Te-Chao Fang ◽  
Yuh-Feng Lin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glomerular Filtration Rate ◽  
Brown Adipose Tissue ◽  
Glomerular Filtration ◽  
Plasminogen Activator ◽  
Mouse Models ◽  
Filtration Rate ◽  
Obese Mouse ◽  
Adipose Tissues ◽  
Brown Adipose

In recent decades, the obesity epidemic has resulted in morbidity and mortality rates increasing globally. In this study, using obese mouse models, we investigated the relationship among urokinase plasminogen activator (uPA), metabolic disorders, glomerular filtration rate, and adipose tissues. Two groups, each comprised of C57BL/6J and BALB/c male mice, were fed a chow diet (CD) and a high fat diet (HFD), respectively. Within the two HFD groups, half of each group were euthanized at 8 weeks (W8) or 16 weeks (W16). Blood, urine and adipose tissues were collected and harvested for evaluation of the effects of obesity. In both mouse models, triglyceride with insulin resistance and body weight increased with duration when fed a HFD in comparison to those in the groups on a CD. In both C57BL/6J and BALB/c HFD mice, levels of serum uPA initially increased significantly in the W8 group, and then the increment decreased in the W16 group. The glomerular filtration rate declined in both HFD groups. The expression of uPA significantly decreased in brown adipose tissue (BAT), but not in white adipose tissue, when compared with that in the CD group. The results suggest a decline in the expression of uPA in BAT in obese m models as the serum uPA increases. There is possibly an association with BAT fibrosis and dysfunction, which may need further study.

W1854 Roux-en-Y Gastric Bypass Activates Brown Adipose Tissue and Increases Energy Expenditure in Obese Mice

2010 ◽  
Vol 138 (5) ◽  
pp. S-754 ◽  
Author(s):  
Nicholas Stylopoulos ◽  
Xiao B. Zhang ◽  
Anna-Liisa Brownell ◽  
Lee M. Kaplan
Keyword(s):  
Gastric Bypass ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Obese Mice ◽  
Brown Adipose
Sign in / Sign up

Export Citation Format

Share Document