Increased expression of glucose transporter GLUT-4 in brown adipose tissue of fasted rats after cold exposure

1993 ◽  
Vol 264 (6) ◽  
pp. E890-E895 ◽  
Author(s):  
Y. Shimizu ◽  
H. Nikami ◽  
K. Tsukazaki ◽  
U. F. Machado ◽  
H. Yano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
Cold Exposure ◽  
De Novo ◽  
Mrna Levels ◽  
Glut 4 ◽  
Increase Glucose Uptake ◽  
Brown Adipose ◽  
Stimulation Of

Cold exposure has been shown to increase glucose uptake specifically in brown adipose tissue (BAT), the major site for sympathetically controlled metabolic heat production. In this study, the relationship between glucose uptake and glucose transporters (GLUT) was examined in rats exposed to cold for various periods. To minimize the stimulatory effect of circulating insulin, all animals were starved for 20-24 h before the measurements. Acute (4 h) cold exposure had no effect on protein and mRNA levels of GLUT-4, the predominant isoform of GLUT in BAT, despite a significant increase in cellular glucose uptake. Prolonged (1-10 days) cold exposure produced a parallel increase in GLUT-4 expression and glucose uptake in BAT. In contrast, cold exposure had no noticeable effect on GLUT-1, another isoform of GLUT in BAT, and on GLUT-4 in other insulin-sensitive tissues such as white adipose tissue and muscles. The increased glucose uptake and GLUT-4 expression were completely abolished after surgical sympathetic denervation. These findings suggest that cold exposure increases glucose uptake in BAT by at least two distinct mechanisms, both of which are dependent on sympathetic nerve: 1) an increase in the amount of GLUT-4 due to the stimulation of its de novo synthesis, and 2) an increase without stimulation of GLUT synthesis, probably due to the change in the transport activity of GLUT-4 and/or its translocation from an intracellular pool to the plasma membrane.

Enhanced gene expression of endothelial nitric oxide synthase in brown adipose tissue during cold exposure

2002 ◽  
Vol 282 (2) ◽  
pp. R623-R626 ◽  
Author(s):  
Kazue Kikuchi-Utsumi ◽  
Bihu Gao ◽  
Hiroshi Ohinata ◽  
Masaaki Hashimoto ◽  
Noriyuki Yamamoto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Inos Mrna ◽  
No Production ◽  
Mrna Levels ◽  
Cold Stimulation ◽  
Brown Adipose ◽  
Enos Mrna

It has been shown that norepinephrine (NE) can mediate vasodilatation by stimulating the production of nitric oxide (NO) in brown adipose tissue (BAT), resulting in an increase in BAT blood flow. We speculated that constitutive NO synthase (NOS) is involved in this NO production. However, it is not known whether constitutive NOS is expressed in BAT. To answer this question, we assessed the expression of two types of constitutive NOS, endothelial (eNOS) and neuronal NOS (nNOS), in BAT of rats. eNOS was abundantly expressed in both BAT and isolated brown adipocytes, whereas nNOS was not. Cold exposure, which is known to stimulate NE release from sympathetic nerve terminals in BAT, led to a significant increase in eNOS mRNA in this tissue. In contrast, very low levels of inducible NOS (iNOS) mRNA were expressed, and cold stimulation failed to increase iNOS mRNA levels in BAT. These results suggest that eNOS is the primary isoform that is responsible for NO production in BAT and that its expression may be under sympathetic control.

Cold exposure potentiates the effect of insulin on in vivo glucose uptake

1987 ◽  
Vol 253 (2) ◽  
pp. E179-E186 ◽  
Author(s):  
A. L. Vallerand ◽  
F. Perusse ◽  
L. J. Bukowiecki
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
Cold Exposure ◽  
Skeletal Muscles ◽  
Insulin Injection ◽  
Peripheral Tissues ◽  
Brown Adipose ◽  
Insulin Responses

The effects of cold exposure (48 h at 4 degrees C) and insulin injection (0.5 U/kg iv) on the rates of net 2-[3H]deoxyglucose uptake (Ki) in peripheral tissues were investigated in warm-acclimated rats (25 degrees C). Cold exposure and insulin treatment independently increased Ki values in skeletal muscles (soleus, extensor digitorum longus, and vastus lateralis), heart, white adipose tissue (subcutaneous, gonadal, and retroperitoneal), and brown adipose tissue (P less than 0.01). The effects of cold exposure were particularly evident in brown adipose tissue where the Ki increased greater than 100 times. When the two treatments were combined (insulin injection in cold-exposed rats), it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an "insulin-like" effect on Ki that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake.

scholarly journals ChREBP-β regulates thermogenesis in brown adipose tissue

2020 ◽  
Vol 245 (3) ◽  
pp. 343-356 ◽  
Author(s):  
Chunchun Wei ◽  
Xianhua Ma ◽  
Kai Su ◽  
Shasha Qi ◽  
Yuangang Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Critical Role ◽  
Active Form ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Brown Adipose ◽  
Metabolic Remodeling

Brown adipose tissue (BAT) plays a critical role in energy expenditure by uncoupling protein 1 (UCP1)-mediated thermogenesis. Carbohydrate response element-binding protein (ChREBP) is one of the key transcription factors regulating de novo lipogenesis (DNL). As a constitutively active form, ChREBP-β is expressed at extremely low levels. Up to date, its functional relevance in BAT remains unclear. In this study, we show that ChREBP-β inhibits BAT thermogenesis. BAT ChREBP-β mRNA levels were elevated upon cold exposure, which prompted us to generate a mouse model overexpressing ChREBP-β specifically in BAT using the Cre/LoxP approach. ChREBP-β overexpression led to a whitening phenotype of BAT at room temperature, as evidenced by increased lipid droplet size and decreased mitochondrion content. Moreover, BAT thermogenesis was inhibited upon acute cold exposure, and its metabolic remodeling induced by long-term cold adaptation was significantly impaired by ChREBP-β overexpression. Mechanistically, ChREBP-β overexpression downregulated expression of genes involved in mitochondrial biogenesis, autophagy, and respiration. Furthermore, thermogenic gene expression (e.g. Dio2, UCP1) was markedly inhibited in BAT by the overexpressed ChREBP-β. Put together, our work points to ChREBP-β as a negative regulator of thermogenesis in brown adipocytes.

scholarly journals Mapping of human brown adipose tissue in lean and obese young men

2017 ◽  
Vol 114 (32) ◽  
pp. 8649-8654 ◽  
Author(s):  
Brooks P. Leitner ◽  
Shan Huang ◽  
Robert J. Brychta ◽  
Courtney J. Duckworth ◽  
Alison S. Baskin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Body Mass ◽  
Cold Exposure ◽  
Young Men ◽  
Total Body Mass ◽  
Fat Depots ◽  
Increase Glucose Uptake ◽  
Brown Adipose ◽  
Wide Range

Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m2; 8 obese, BMI 34.8 ± 3.3 kg/m2] after 5 h of tolerable cold exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1–71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT—cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal—with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.

scholarly journals Glucose uptake in brown fat cells is dependent on mTOR complex 2–promoted GLUT1 translocation

2014 ◽  
Vol 207 (3) ◽  
pp. 365-374 ◽  
Author(s):  
Jessica M. Olsen ◽  
Masaaki Sato ◽  
Olof S. Dallner ◽  
Anna L. Sandström ◽  
Didier F. Pisani ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
De Novo ◽  
De Novo Synthesis ◽  
Mechanistic Target Of Rapamycin ◽  
Brown Adipose ◽  
Phosphoinositide 3 Kinase ◽  
Very High ◽  
Different Parts

Brown adipose tissue is the primary site for thermogenesis and can consume, in addition to free fatty acids, a very high amount of glucose from the blood, which can both acutely and chronically affect glucose homeostasis. Here, we show that mechanistic target of rapamycin (mTOR) complex 2 has a novel role in β3-adrenoceptor–stimulated glucose uptake in brown adipose tissue. We show that β3-adrenoceptors stimulate glucose uptake in brown adipose tissue via a signaling pathway that is comprised of two different parts: one part dependent on cAMP-mediated increases in GLUT1 transcription and de novo synthesis of GLUT1 and another part dependent on mTOR complex 2–stimulated translocation of newly synthesized GLUT1 to the plasma membrane, leading to increased glucose uptake. Both parts are essential for β3-adrenoceptor–stimulated glucose uptake. Importantly, the effect of β3-adrenoceptor on mTOR complex 2 is independent of the classical insulin–phosphoinositide 3-kinase–Akt pathway, highlighting a novel mechanism of mTOR complex 2 activation.

The PPARγ agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake

2009 ◽  
Vol 296 (5) ◽  
pp. R1327-R1335 ◽  
Author(s):  
William T. Festuccia ◽  
Pierre-Gilles Blanchard ◽  
Véronique Turcotte ◽  
Mathieu Laplante ◽  
Meltem Sariahmetoglu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
Mrna Levels ◽  
Pparγ Agonist ◽  
Brown Adipose ◽  
Lipin 1 ◽  
The Impact

We investigated the mechanisms whereby peroxisome proliferator-activated receptor-γ (PPARγ) agonism affects glucose and lipid metabolism in brown adipose tissue (BAT) by studying the impact of PPARγ activation on BAT glucose uptake and metabolism, lipogenesis, and mRNA levels plus activities of enzymes involved in triacylglycerol (TAG) synthesis. Interscapular BAT of rats treated or not with rosiglitazone (15 mg·kg−1·day−1, 7 days) was evaluated in vivo for glucose uptake and lipogenesis and in vitro for glucose metabolism, gene expression, and activities of glycerolphosphate acyltransferase (GPAT), phosphatidate phosphatase-1 (PAP or lipin-1), and diacylglycerol acyltransferase (DGAT). Rosiglitazone increased BAT mass without affecting whole tissue glucose uptake. BAT glycogen content (−80%), its synthesis from glucose (−50%), and mRNA levels of UDP-glucose pyrophosphorylase (−40%), which generates UDP-linked glucose for glycogen synthesis, were all reduced by rosiglitazone. In contrast, BAT TAG-glycerol synthesis in vivo and glucose incorporation into TAG-glycerol in vitro were stimulated by the agonist along with the activities and mRNA levels of glycerol 3-phosphate-generating phosphoenolpyruvate carboxykinase and glycerokinase. Furthermore, rosiglitazone markedly increased the activities of GPAT and DGAT but not those of lipin-1-mediated PAP-1, enzymes involved in the sequential acylation of glycerol 3-phosphate and TAG synthesis. Because an adequate supply of fatty acids is essential for BAT nonshivering thermogenesis, the enhanced ability of BAT to synthesize TAG under PPARγ activation may constitute an important mechanism by which lipid substrates are stored in preparation for an eventual thermogenic activation.

scholarly journals Effect of diabetes and fasting on GLUT-4 (muscle/fat) glucose-transporter expression in insulin-sensitive tissues. Heterogeneous response in heart, red and white muscle

1992 ◽  
Vol 282 (3) ◽  
pp. 765-772 ◽  
Author(s):  
M Camps ◽  
A Castelló ◽  
P Muñoz ◽  
M Monfar ◽  
X Testar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
White Muscle ◽  
Glucose Transporter ◽  
Mrna Levels ◽  
Glut 4 ◽  
Brown Adipose ◽  
Red Muscle

1. GLUT-4 glucose-transporter protein and mRNA levels were assessed in heart, red muscle and white muscle, as well as in brown and white adipose tissue from 7-day streptozotocin-induced diabetic and 48 h-fasted rats. 2. In agreement with previous data, white adipose tissue showed a substantial decrease in GLUT-4 mRNA and protein levels in response to both diabetes and fasting. Similarly, GLUT-4 mRNA and protein markedly decreased in brown adipose tissue in both insulinopenic conditions. 3. Under control conditions, the level of expression of GLUT-4 protein content differed substantially in heart, red and white skeletal muscle. Thus GLUT-4 protein was maximal in heart, and red muscle had a greater GLUT-4 content compared with white muscle. In spite of the large differences in GLUT-4 protein content, GLUT-4 mRNA levels were equivalent in heart and red skeletal muscle. 4. In heart, GLUT-4 mRNA decreased to a greater extent than GLUT-4 protein in response to diabetes and fasting. In contrast, red muscle showed a greater decrease in GLUT-4 protein than in mRNA in response to diabetes or fasting, and in fact no decrease in GLUT-4 mRNA content was detectable in fasting. On the other hand, preparations of white skeletal muscle showed a substantial increase in GLUT-4 mRNA under both insulinopenic conditions, and that was concomitant to either a modest decrease in GLUT-4 protein in diabetes or to no change in fasting. 5. These results indicate that (a) the effects of diabetes and fasting are almost identical and lead to changes in GLUT-4 expression that are tissue-specific, (b) white adipose tissue, brown adipose tissue and heart respond similarly to insulin deficiency by decreasing GLUT-4 mRNA to a larger extent than GLUT-4 protein, and (c) red and white skeletal muscle respond to insulinopenic conditions in a heterogeneous manner which is characterized by enhanced GLUT-4 mRNA/protein ratios.

Stimulatory effects of cold exposure and cold acclimation on glucose uptake in rat peripheral tissues

1990 ◽  
Vol 259 (5) ◽  
pp. R1043-R1049 ◽  
Author(s):  
A. L. Vallerand ◽  
F. Perusse ◽  
L. J. Bukowiecki
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Cold Acclimation ◽  
Cold Exposure ◽  
Skeletal Muscles ◽  
Contractile Activity ◽  
Peripheral Tissues ◽  
Brown Adipose ◽  
Shivering Thermogenesis ◽  
Stimulation Of

The effects of cold exposure on the net rates of 2-[3H]deoxy-D-glucose uptake (Ki) in rat peripheral tissues were investigated comparatively in warm- and cold-acclimated animals to determine whether cold acclimation induces regulatory alterations in glucose metabolism. Acute exposure of warm-acclimated (25 degrees C) rats to cold (48 h at 5 degrees C) markedly increased the Ki values in red and white skeletal muscles (2-5 times), in the heart (8 times), in several white adipose tissue (WAT) depots (4-20 times), and in brown adipose tissue (BAT) (110 times). After cold acclimation (3 wk at 5 degrees C), the Ki values further increased in the heart (15 times) and WAT (up to 29 times) but decreased in BAT (36 times). Remarkably, glucose uptake was still increased in muscles of cold-exposed/cold-acclimated animals (that do not shiver), demonstrating that enhanced glucose uptake may occur in muscles in the absence of shivering thermogenesis (or contractile activity). When cold-acclimated rats were returned to the warm for 18 h, the Ki values of all tissues, except WAT, returned to control levels. Cold exposure synergistically potentiated the stimulation of tissue glucose uptake induced by a maximal effective dose of insulin (0.5 U/kg iv) in warm- as well as in cold-acclimated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic norepinephrine infusion stimulates glucose uptake in white and brown adipose tissues

1994 ◽  
Vol 266 (3) ◽  
pp. R914-R920 ◽  
Author(s):  
X. Liu ◽  
F. Perusse ◽  
L. J. Bukowiecki
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
Cold Exposure ◽  
Skeletal Muscles ◽  
Interscapular Brown Adipose Tissue ◽  
Peripheral Tissues ◽  
Glucose Levels ◽  
Brown Adipose

Cold exposure activates the sympathetic nervous system and markedly stimulates glucose uptake in rat peripheral tissues [A. L. Vallerand, F. Perusse, and L. J. Bukowiecki. Am. J. Physiol 259 (Regulatory Integrative Comp. Physiol. 28): R1043-R1049, 1990]. To test whether norepinephrine (NE) mimics the effects of cold exposure, we estimated the effects of chronic NE treatment on tissue glucose uptake by determining the glucose metabolic index using the 2-[1,2-3H(N)]deoxy-D-glucose method. NE was administered in conscious rats at various doses (ranging from 1.9 to 25.1 nmol.kg-1.min-1) during 4 days via minipumps implanted subcutaneously. At doses > 10 nmol.kg-1.min-1, NE maximally stimulated glucose uptake in interscapular brown adipose tissue (approximately 50 times above controls) and epididymal white adipose tissue (approximately 3 times above controls). NE infusion (18.8 nmol.kg-1.min-1) increased the circulating levels of NE from 1.1 +/- 0.1 to 19.2 +/- 0.4 nM (P < 0.001), which is in the range of concentrations for the stimulatory effects of NE on glucose uptake in isolated brown adipocytes. At all concentrations tested, NE infusion did not stimulate glucose uptake in the heart and skeletal muscles. NE treatment did not significantly alter plasma insulin or glucose levels but increased the concentration of circulating free fatty acids. The capacity of brown adipose tissue for NE stimulation of glucose uptake (expressed per g of tissue) was much higher than that of white adipose tissue (100 times), various types of white or red skeletal muscles (10-80 times), or the heart (3-4 times).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals PPARγ activation attenuates cold-induced upregulation of thyroid status and brown adipose tissue PGC-1α and D2

2012 ◽  
Vol 303 (12) ◽  
pp. R1277-R1285 ◽  
Author(s):  
William T. Festuccia ◽  
Pierre-Gilles Blanchard ◽  
Thiago B. Oliveira ◽  
Juliana Magdalon ◽  
Vivian A. Paschoal ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Sympathetic Activity ◽  
Mrna Levels ◽  
Thyroid Status ◽  
Iodothyronine Deiodinase ◽  
Camp Content ◽  
Adrenergic Signaling ◽  
Brown Adipose

Here, we investigated whether pharmacological PPARγ activation modulates key early events in brown adipose tissue (BAT) recruitment induced by acute cold exposure with the aim of unraveling the interrelationships between sympathetic and PPARγ signaling. Sprague-Dawley rats treated or not with the PPARγ ligand rosiglitazone (15 mg·kg−1·day−1, 7 days) were kept at 23°C or exposed to cold (5°C) for 24 h and evaluated for BAT gene expression, sympathetic activity, thyroid status, and adrenergic signaling. Rosiglitazone did not affect the reduction in body weight gain and the increase in feed efficiency, V̇o2, and BAT sympathetic activity induced by 24-h cold exposure. Rosiglitazone strongly attenuated the increase in serum total and free T4 and T3 levels and BAT iodothyronine deiodinase type 2 (D2) and PGC-1α mRNA levels and potentiated the reduction in BAT thyroid hormone receptor (THR) β mRNA levels induced by cold. Administration of T3 to rosiglitazone-treated rats exacerbated the cold-induced increase in energy expenditure but did not restore a proper activation of D2 and PGC-1α, nor further increased uncoupling protein 1 expression. Regarding adrenergic signaling, rosiglitazone did not affect the changes in BAT cAMP content and PKA activity induced by cold. Rosiglitazone alone or in combination with cold increased CREB binding to DNA, but it markedly reduced the expression of one of its major coactivators, CREB binding protein. In conclusion, pharmacological PPARγ activation impairs short-term cold elicitation of BAT adrenergic and thyroid signaling, which may result in abnormal tissue recruitment and thermogenic activity.

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