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 ◽  
...  

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.

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 308 ◽  
Author(s):  
Hyo-Geun Lee ◽  
Yu An Lu ◽  
Xining Li ◽  
Ji-Min Hyun ◽  
Hyun-Soo Kim ◽  
...  

Obesity is a serious metabolic syndrome characterized by high levels of cholesterol, lipids in the blood, and intracellular fat accumulation in adipose tissues. It is known that the suppression of adipogenic protein expression is an effective approach for the treatment of obesity, and regulates fatty acid storage and transportation in adipose tissues. The 60% ethanol extract of Grateloupia elliptica (GEE), a red seaweed from Jeju Island in Korea, was shown to exert anti-adipogenic activity in 3T3-L1 cells and in mice with high-fat diet (HFD)-induced obesity. GEE inhibited intracellular lipid accumulation in 3T3-L1 cells, and significantly reduced expression of adipogenic proteins. In vivo experiments indicated a significant reduction in body weight, as well as white adipose tissue (WAT) weight, including fatty liver, serum triglycerides, total cholesterol, and leptin contents. The expression of the adipogenic proteins, SREBP-1 and PPAR-γ, was significantly decreased by GEE, and the expression of the metabolic regulator protein was increased in WAT. The potential of GEE was shown in WAT, with the downregulation of PPAR-γ and C/EBP-α mRNA; in contrast, in brown adipose tissue (BAT), the thermogenic proteins were increased. Collectively, these research findings suggest the potential of GEE as an effective candidate for the treatment of obesity-related issues via functional foods or pharmaceutical agents.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Juliane Weiner ◽  
Mathias Kranz ◽  
Nora Klöting ◽  
Anne Kunath ◽  
Karen Steinhoff ◽  
...  

1984 ◽  
Vol 62 (7) ◽  
pp. 631-636 ◽  
Author(s):  
N. Bégin-Heick ◽  
H. M. C. Heick

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.


1982 ◽  
Vol 60 (9) ◽  
pp. 910-916 ◽  
Author(s):  
Nicole Bégin-Heick ◽  
H. M. C. Heick

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.


1982 ◽  
Vol 206 (3) ◽  
pp. 667-669 ◽  
Author(s):  
P. John Weaire ◽  
Tazeen F. Kanagasabai

Cycloplasmic preparations from brown and white adipose tissues were assayed for three lipogenic enzymes throughout a programme of starvation followed by refeeding on either a normal or a white-bread diet. In the brown adipose tissue of rats fed on a white-bread diet the three enzymes were elevated to levels significantly higher than those in white adipose tissue.


2017 ◽  
Vol 115 (1) ◽  
pp. 174-179 ◽  
Author(s):  
Rosa T. Branca ◽  
Andrew McCallister ◽  
Hong Yuan ◽  
Amir Aghajanian ◽  
James E. Faber ◽  
...  

Detection and quantification of brown adipose tissue (BAT) mass remains a major challenge, as current tomographic imaging techniques are either nonspecific or lack the necessary resolution to quantify BAT mass, especially in obese phenotypes, in which this tissue may be present but inactive. Here, we report quantification of BAT mass by xenon-enhanced computed tomography. We show that, during stimulation of BAT thermogenesis, the lipophilic gas xenon preferentially accumulates in BAT, leading to a radiodensity enhancement comparable to that seen in the lungs. This enhancement is mediated by a selective reduction in BAT vascular resistance, which greatly increases vascular perfusion of BAT. This enhancement enables precise identification and quantification of BAT mass not only in lean, but also in obese, mouse phenotypes, in which this tissue is invisible to conventional tomographic imaging techniques. The method is developed and validated in rodents and then applied in macaques to assess its feasibility in larger species.


2008 ◽  
Vol 295 (2) ◽  
pp. E514-E518 ◽  
Author(s):  
Toyoshi Endo ◽  
Tetsuro Kobayashi

C.RF- Tshrhyt/hyt mice have a mutated thyroid-stimulating hormone receptor (TSHR), and, without thyroid hormone supplementation, these mice develop severe hypothyroidism. When hypothyroid Tshrhyt/hyt mice were exposed to cold (4°C), rectal temperature rapidly dropped to 23.9 ± 0.40°C at 90 min, whereas the wild-type mice temperatures were 37.0 ± 0.15°C. When we carried out functional rat TSHR gene transfer in the brown adipose tissues by plasmid injection combined with electroporation, there was no effect on the serum levels of thyroxine, although rectal temperature of the mice transfected with pcDNA3.1/Zeo-rat TSHR 90 min after cold exposure remained at 34.6 ± 0.34°C, which was significantly higher than that of Tshrhyt/hyt mice. Transfection of TSHR cDNA increased mRNA and protein levels of uncoupling protein-1 (UCP-1) in brown adipose tissues, and the weight ratio of brown adipose tissue to overall body weight also increased. Exogenous thyroid hormone supplementation to Tshrhyt/hyt mice restored rectal temperature 90 min after exposure to cold (36.8 ± 0.10°C). These results indicate that not only thyroid hormone but also thyroid-stimulating hormone (TSH)/TSHR are involved in the expression mechanism of UCP-1 in mouse brown adipose tissue. TSH stimulates thermogenesis and functions to protect a further decrease in body temperature in the hypothyroid state.


1989 ◽  
Vol 9 (1) ◽  
pp. 111-117 ◽  
Author(s):  
Shelagh Wilson

BRL 26830 is a thermogenic β-adrenoceptor agonist which stimulates lipolysis and fatty acid oxidation in vivo. It also stimulates insulin secretion, and hence promotes glucose utilisation in vivo. The effect of this agent on white and brown adipose tissue of the rat was investigated. BRL 26830 increased the rate of fatty acid synthesis in vivo in white adipose tissue by 135% but reduced the rate of fatty acid synthesis in vivo in brown adipose tissue by 78%. The increase was abolished in white adipose tissue of streptozotocin-diabetic rats, indicating that the effect involved a rise in circulating insulin levels. The reduction in fatty acid synthesis in brown adipose tissues was associated with a reduction in the activity of acetyl-CoA carboxylase in the tissue consistent with a direct β-adrenoceptor-mediated effect. BRL 26830 also increased the proportion of pyruvate dehydrogenase in its active form in vivo in brown adipose tissue and this increase was abolished in streptozotocin-diabetic rats. These findings illustrate different sensitivities of white and brown adipose tissues to combined β-adrenergic and insulin stimulation.


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