Cold-induced expression of the metallothionein-1 gene in brown adipose tissue of rats

1996 ◽  
Vol 270 (5) ◽  
pp. R971-R977 ◽  
Author(s):  
J. H. Beattie ◽  
D. J. Black ◽  
A. M. Wood ◽  
P. Trayhurn

Heat production by brown adipose tissue (BAT) is important for thermoregulation in a cold environment. During thermogenesis, oxygen utilization increases, with an associated rise in free radical generation. Our objective was to investigate the expression of metallothionein (MT), which is thought to have an antioxidant role in BAT of rates transferred from 25 to 6 degrees C for 6 or 24 h or maintained at 25 degrees C throughout the study (control group). For comparison, MT expression was also measured in white adipose tissue (WAT), liver, and kidney. MT-1 mRNA and 18S rRNA were measured by Northern blotting using specific digoxigenin-labeled antisense oligonucleotide probes with chemiluminescence detection, and MT-1 protein was determined by radioimmunoassay. MT-1 mRNA in BAT increased after 6 h, and the mRNA level after 24 h was equivalent to that in liver 6 h after injection of rats with 10 mg Zn/kg. By 24 h, liver and kidney MT-1 protein had increased relative to the controls by 3- and 1.4-fold, respectively, but in BAT the relative induction was 16-fold. Zn injection did not affect BAT MT-1. As with MT-1 protein, Zn in BAT increased only after 24-h cold exposure. WAT MT-1 was not affected by any treatment. It is concluded that could exposure induces MT-1 in BAT, but in contrast to other tissues induction may be independent of Zn.

1993 ◽  
Vol 291 (1) ◽  
pp. 109-113 ◽  
Author(s):  
R Burcelin ◽  
J Kande ◽  
D Ricquier ◽  
J Girard

We have studied the time course and relative effects of hypoinsulinaemia and hyperglycaemia on concentrations of uncoupling protein (UCP) and glucose transporter (GLUT4) and their mRNAs in brown adipose tissue (BAT) during the early phase of diabetes induced by streptozotocin. Two days after intravenous injection of streptozotocin, plasma insulin concentration was at its lowest and glycaemia was higher than 22 mmol/l. After 3 days, a 60% decrease in BAT UCP mRNA concentration and a 36% decrease in UCP was observed. Concomitantly, there was an 80% decrease in GLUT4 mRNA and a 44% decrease in GLUT4 levels. When hyperglycaemia was prevented by infusing phlorizin into diabetic rats, BAT UCP mRNA and protein levels were further decreased (respectively 90% and 60% lower than in control rats). In contrast, the marked decreases in GLUT4 mRNA and protein concentrations in BAT were similar in hyperglycaemic and normoglycaemic diabetic rats. Infusion of physiological amounts of insulin restored normoglycaemia in diabetic rats, and BAT UCP and GLUT4 mRNA and protein concentrations were maintained at the level of control rats. When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease. This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT. Hyperglycaemia partially prevents the rapid decrease in concentration of UCP and its mRNA observed in insulinopenic diabetes whereas it did not affect the decrease in GLUT4 mRNA and protein concentration. It is suggested that UCP is produced by a glucose-dependent gene.


1989 ◽  
Vol 122 (2) ◽  
pp. 553-556 ◽  
Author(s):  
M. Puig-Domingo ◽  
J. M. Guerrero ◽  
A. Menéndez-Pelaez ◽  
R. J. Reiter

ABSTRACT The response of type-II thyroxine 5′-deiodinase (5′-DII)DII) to melatonin treatment was studied in the Syrian hamster. Male hamsters were treated for 15 days with a s.c. pellet containing melatonin, and 5′-DII activity in brown adipose tissue, anterior pituitary gland, Harderian gland and pineal gland was measured using a radioenzymatic technique. Melatonin-treated animals exhibited enhanced 5′-DII activity restricted to brown adipose tissue; the increase was threefold above the values measured in the control group. Serum concentrations of thyroid hormones were unaffected by melatonin treatment. We conclude that the stimulatory effect of melatonin on type-II thyroxine 5′-deiodination is specifically directed to the isoenzyme located in brown adipose tissue and is not accompanied by changes in serum thyroid hormones. Journal of Endocrinology (1989) 122, 553–556


1987 ◽  
Vol 252 (1) ◽  
pp. R160-R165 ◽  
Author(s):  
C. J. Billington ◽  
T. J. Bartness ◽  
J. Briggs ◽  
A. S. Levine ◽  
J. E. Morley

Despite long-standing observations of a whole-body thermogenic effect of glucagon, the role of glucagon in activating thermogenesis in brown adipose tissue has not often been studied. We investigated the ability of administered glucagon to produce alterations in brown adipose tissue similar to changes produced by accepted stimuli of brown fat activity: cold, norepinephrine, and overfeeding. Eighteen days of glucagon injections (1 mg/kg) to male Sprague-Dawley rats produced, relative to saline-injected controls, decreases in feed efficiency and increases in brown adipose tissue weight, protein content, DNA content, and mitochondrial mass as reflected in cytochrome oxidase activity. The observed changes were similar, though of lesser magnitude, to changes produced in these same parameters induced by administration of norepinephrine (250 micrograms/kg) for a positive control group. Four days of glucagon administration (1 mg/kg) produced increases in specific activity of cytochrome oxidase and lipoprotein lipase. After 8 days of glucagon administration, changes in whole-pad activity similar to those seen with 18 days of administration were present. Glucagon also increased whole-pad lipoprotein lipase activity after 4 and 8 days. Surgically denervated interscapular brown adipose tissue retained its ability to respond to exogenous glucagon, though the magnitude of the response was diminished. Guanosine 5'-diphosphate (GDP) binding to brown adipose tissue mitochondria was measured as an assessment of functional state after 5 days of glucagon (1 mg/kg). There was an increase in GDP binding relative to controls whether expressed as picomoles per milligram mitochondrial protein or nanomoles per pad.(ABSTRACT TRUNCATED AT 250 WORDS)


2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Wenjing You ◽  
Ziye Xu ◽  
Ye Sun ◽  
Teresa G. Valencak ◽  
Yizhen Wang ◽  
...  

Abstract Stress can lead to obesity and metabolic dysfunction, but the underlying mechanisms are unclear. Here we identify GADD45α, a stress-inducible histone folding protein, as a potential regulator for brown adipose tissue biogenesis. Unbiased transcriptomics data indicate a positive correlation between adipose Gadd45a mRNA level and obesity. At the cellular level, Gadd45a knockdown promoted proliferation and lipolysis of brown adipocytes, while Gadd45a overexpression had the opposite effects. Consistently, using a knockout (Gadd45a−/−) mouse line, we found that GADD45α deficiency inhibited lipid accumulation and promoted expression of thermogenic genes in brown adipocytes, leading to improvements in insulin sensitivity, glucose uptake, energy expenditure. At the molecular level, GADD45α deficiency increased proliferation through upregulating expression of cell cycle related genes. GADD45α promoted brown adipogenesis via interacting with PPARγ and upregulating its transcriptional activity. Our new data suggest that GADD45α may be targeted to promote non-shivering thermogenesis and metabolism while counteracting obesity.


1981 ◽  
Vol 240 (4) ◽  
pp. E379-E383 ◽  
Author(s):  
C. Senault ◽  
G. Cherqui ◽  
M. Cadot ◽  
R. Portet

Seven-week-old Long-Evans rats were acclimated to a constant temperature of either 28 degrees C (control group) or 5 degrees C (cold-acclimated group). Cold acclimation induced a 70% increase in the interscapular brown adipose tissue (IBAT) relative mass, a 35% increase in DNA content, and a 44% decrease in triglyceride (TG) content, which resulted in a 51% decrease of the TG/DNA ratio. A procedure is described by which brown fat cells were isolated, with a yield of 21% from the IBAT of the control group and of 38% in the cold-acclimated group. In both groups, the brown fat cells accounted for 35-37% of the total cells in the tissue. Cold acclimation induced decreases in the mean fat cell diameter (about 20%), the mean fat cell TG content (50%), and the fat cell TG/DNA ratio (50%). The total number of IBAT fat cells was significantly increased in cold-acclimated rats. It is concluded that cold acclimation involves a hyperplasia of the IBAT, associated with a decrease of fat cell size without any alteration of the fat cell-to-nonfat cell ratio.


Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3577-3588 ◽  
Author(s):  
Yuri Fujimoto ◽  
Yoshimi Nakagawa ◽  
Aoi Satoh ◽  
Kanako Okuda ◽  
Akiko Shingyouchi ◽  
...  

Transcription factor E3 (TFE3) is a transcription factor that binds to E-box motifs and promotes energy metabolism-related genes. We previously reported that TFE3 directly binds to the insulin receptor substrate-2 promoter in the liver, resulting in increased insulin response. However, the role of TFE3 in other tissues remains unclear. In this study, we generated adipose-specific TFE3 transgenic (aP2-TFE3 Tg) mice. These mice had a higher weight of white adipose tissue (WAT) and brown adipose tissue than wild-type (WT) mice under fasting conditions. Lipase activity in the WAT in these mice was lower than that in the WT mice. The mRNA level of adipose triglyceride lipase (ATGL), the rate-limiting enzyme for adipocyte lipolysis, was significantly decreased in aP2-TFE3 Tg mice. The expression of Foxo1, which directly activates ATGL expression, was also suppressed in transgenic mice. Promoter analysis confirmed that TFE3 suppressed promoter activities of the ATGL gene. In contrast, G0S2 and Perilipin1, which attenuate ATGL activity, were higher in transgenic mice than in WT mice. These results indicated that the decrease in lipase activity in adipose tissues was due to a decrease in ATGL expression and suppression of ATGL activity. We also showed that thermogenesis was suppressed in aP2-TFE3 Tg mice. The decrease in lipolysis in WAT of aP2-TFE3 Tg mice inhibited the supply of fatty acids to brown adipose tissue, resulting in the inhibition of the expression of thermogenesis-related genes such as UCP1. Our data provide new evidence that TFE3 regulates lipid metabolism by controlling the gene expression related to lipolysis and thermogenesis in adipose tissue.


2021 ◽  
Author(s):  
Yan Zeng ◽  
Lei Gao ◽  
Shuying Shao ◽  
Xiaoshuai Chen ◽  
Ping Zhang ◽  
...  

Abstract Rationale and Objectives: We aimed to evaluate the effect of exercise on brown adipose tissue (BAT) volumes and T2 values in mice. Materials and Methods Twenty-five female Kunming mice were divided into two groups, a running group (n = 5) and a control group (n = 20). After 4 months, all magnetic resonance imaging (MRI) scans of mice were performed on a 7 Tesla (7T) MR scanner with T2-weighted imaging (T2WI) and a T2 mapping sequence. Interscapular brown adipose tissue (BAT) volumes and T2 values were measured. To reduce the impact of weight on the results, we compared the ratio of BAT volumes to body weights (V/W). The data are expressed as mean ± SD, the BAT V/W and T2 values were compared between the control and running groups using the Wilcoxon rank-sum test, P < 0.05 were considered statistically significant. Results Interscapular BAT volumes of the running group (n = 5) and control group (n = 20) were (180.09ml ± 59.80 ml) and (99.98ml ± 35.05ml), respectively. The V/W ratios of the running and control groups were (3.83ml/g ± 0.78ml/g) and (2.17ml/g ± 0.56ml/g), respectively. Interscapular BAT T2 values of the running and control groups were (76.07ms ± 10.82ms) and (61.22ms ± 15.98ms), respectively. Significant differences were found in the BAT V/W ratios (P = 0.0003, P < 0.001) and T2 values between the two groups (P = 0.0096, P < 0.05). BAT volume correlated positively with BAT T2 value (r = 0.75, p = 0.00002). Conclusions MRI is a non-invasive and quantitative method for identifying BAT, especially at ultra-high field like 7T. Long-term running increases BAT volume and T2 value, what's more, BAT volume correlates positively with BAT T2 value.


2020 ◽  
Vol 105 (4) ◽  
pp. 1176-1185
Author(s):  
Zahraa Abdul Sater ◽  
Abhishek Jha ◽  
Ahmed Hamimi ◽  
Adel Mandl ◽  
Iris R Hartley ◽  
...  

Abstract Context Pheochromocytomas/paragangliomas (PPGLs) are neuroendocrine tumors that can secrete norepinephrine (NE). Brown adipose tissue (BAT) activation is mediated through the action of NE on β-adrenoceptors (β-ARs). In some malignancies, BAT activation is associated with higher cancer activity. Objective To study the relationship between BAT activation and PPGL clinical outcomes. Design A retrospective case-control study that included 342 patients with PPGLs who underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18F-FDG PET/CT) imaging at the National Institutes of Health (NIH). We excluded all patients with parasympathetic tumors and those who underwent 18F-FDG PET/CT after PPGL resection. Scans of 205 patients were reviewed by 2 blinded nuclear medicine physicians; 16 patients had BAT activation on 18F-FDG PET/CT [7.80%; age 27.50 (15.00–45.50) years; 10 female/6 male; body mass index [BMI] 24.90 [19.60–25.35] kg/m2). From the remaining 189 patients, we selected 36 matched controls (age 34.4 [25.4–45.5] years; 21 female/15 male; BMI 25.0 [22.0–26.0] kg/m2). Primary Outcome Measure Overall survival. Results The presence of active BAT on 18F-FDG PET/CT was associated with decreased overall survival when compared with the control group (HRz 5.80; 95% CI, 1.05–32.05; P = 0.02). This association remained significant after adjusting for the SDHB mutation. Median plasma NE in the BAT group was higher than the control group [4.65 vs 0.55 times above the upper limit of normal; P &lt; 0.01]. There was a significant association between higher plasma NE levels and mortality in PPGLs in both groups. Conclusions Our findings suggest that the detection of BAT activity in PPGL patients is associated with higher mortality. We suggest that BAT activation could either be reflecting or contributing to a state of increased host stress that may predict poor outcome in metastatic PPGL.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Pengyu Fu ◽  
Rongxin Zhu ◽  
Jie Jia ◽  
Yang Hu ◽  
Chengjun Wu ◽  
...  

Abstract Background High-fat diet (HFD)-induced obesity causes immune cells to infiltrate adipose tissue, leading to chronic inflammation and metabolic syndrome. Brown adipose tissue (BAT) can dissipate the energy produced by lipid oxidation as heat, thereby counteracting obesity. Aerobic exercise activates BAT, but the specific underlying mechanism is still unclear. Methods Male C57BL/6 J mice were divided into a normal diet control group (NC group) and HFD group (H group). After becoming obese, the animals in the H group were subdivided into a control group (HC group) and an exercise group (HE group, with treadmill training). After 4 weeks, the mRNA profile of BAT was determined, and then differentially expressed key genes and pathways were verified in vitro. Results Relative to the NC group, the genes upregulated in the HC group coded mainly for proteins involved in immune system progression and inflammatory and immune responses, while the downregulated genes regulated lipid metabolism and oxidation–reduction. Relative to the HC group, the genes upregulated in the HE group coded for glycolipid metabolism, while those that were downregulated were involved in cell death and apoptosis. VEGF and other signaling pathways were enhanced by aerobic exercise. Interaction analysis revealed that the gene encoding cyclooxygenase 2 (COX2) of the VEGF signaling pathway is central to this process, which was verified by a sympathetic activator (isoprenaline hydrochloride) and COX2 inhibitor (NS-398). Conclusions In mice with HFD-induced obesity, four weeks of aerobic exercise elevated BAT mass and increased the expression of genes related to glycolipid metabolism and anti-inflammatory processes. Several pathways are involved, with COX2 in the VEGF signaling pathway playing a key role.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Ali Khajehlandi ◽  
Amin Mohammadi ◽  
Mojtaba Karimi Fard

Background: The effect of training on the gene expression of GLUT4 and insulin receptor (IR) has been investigated in some studies, but the simultaneous effect of swimming training along with cinnamon consumption is unknown. Objective: This study aimed to examine the effect of six weeks of swimming training with cinnamon consumption on the gene expression of GLUT4 and IR in the brown adipose tissue of diabetic rats. Methods: In this experimental study, 28 diabetic rats were randomly divided into four groups of seven animals, including 1- control (C), 2- cinnamon (Ci), 3- swimming (S), and 4- swimming plus cinnamon (S + Ci). Rats in groups 3 and 4 trained for six weeks and five sessions. Groups 2 and 4 received 200 mg/kg/day. Data were analyzed using one-way analysis of variance and Tukey’s post hoc test at the level of P ≤ 0.05. Results: The gene expression of GLUT4 and IR in the S, Ci, and S + Ci groups was significantly (P = 0.001) higher than the control group. Also, the gene expression of GLUT4 and IR in the S group was significantly (P = 0.001) higher than the Ci and S + Ci groups. Conclusion: Swimming training and cinnamon consumption and their simultaneous implementation had a significant effect on increasing the gene expression of GLUT4 and IR in the brown adipose tissue of diabetic rats. On the other hand, swimming training alone had a greater effect than cinnamon consumption and swimming plus cinnamon consumption.


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