Characterization and regulation of cold-induced heat shock protein expression in mouse brown adipose tissue

1995 ◽  
Vol 269 (1) ◽  
pp. R38-R47 ◽  
Author(s):  
J. M. Matz ◽  
M. J. Blake ◽  
H. M. Tatelman ◽  
K. P. Lavoi ◽  
N. J. Holbrook
Keyword(s):  
Adipose Tissue ◽  
Heat Shock ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Elevated Temperatures ◽  
Uncoupling Protein ◽  
Hsp70 Expression ◽  
Mitochondrial Uncoupling ◽  
Ambient Temperatures ◽  
Brown Adipose

The accumulation of heat shock proteins (HSPs) after the exposure of cells or organisms to elevated temperatures is well established. It is also known that a variety of other environmental and cellular metabolic stressors can induce HSP synthesis. However, few studies have investigated the effect of cold temperature on HSP expression. Here we report that exposure of Institute of Cancer Research (ICR) mice to cold ambient temperatures results in a tissue-selective induction of HSPs in brown adipose tissue (BAT) coincident with the induction of mitochondrial uncoupling protein synthesis. Cold-induced HSP expression is associated with enhanced binding of heat shock transcription factors to DNA, similar to that which occurs after exposure of cells or tissues to heat and other metabolic stresses. Adrenergic receptor antagonists were found to block cold-induced HSP70 expression in BAT, whereas adrenergic agonists induced BAT HSP expression in the absence of cold exposure. These findings suggest that norepinephrine, released in response to cold exposure, induces HSP expression in BAT. Norepinephrine appears to initiate transcription of HSP genes after binding to BAT adrenergic receptors through, as yet, undetermined signal transduction pathways. Thermogenesis results from an increase in activity and synthesis of several metabolic enzymes in BAT of animals exposed to cold challenge. The concomitant increase in HSPs may function to facilitate the translocation and activity of the enzymes involved in this process.

scholarly journals Maternal manipulation of brown adipose tissue and liver development in the ovine fetus during late gestation

1997 ◽  
Vol 77 (6) ◽  
pp. 871-883 ◽  
Author(s):  
Lynne Clarke ◽  
Michael J. Bryant ◽  
Michael A. Lomax ◽  
Michael E. Symonds
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Late Gestation ◽  
Liver Development ◽  
Type I ◽  
Mitochondrial Uncoupling ◽  
Brown Adipose

AbstractWe examined the effect of maternal chronic cold exposure, induced by winter-shearing ewes 4 weeks before their predicted lambing date, on brown adipose tissue (BAT) and liver development in lambs. Fetuses were sampled from under-fed (60% of energy requirements for maintenance and pregnancy of an unshorn ewe) shorn or unshorn ewes at 126,140 and 145 d of gestation. Lambs were sampled from ewes within 2 h of birth. Throughout gestation fetal body, BAT and liver weights were similar in shorn and unshorn groups. The level of GDP binding to mitochondrial uncoupling protein remained low throughout gestation, but increased dramatically after birth. Lambs born to shorn ewes possesd more mitochondrial protein and exhibited a significantly higher total thermogenic activity in BAT. Type I iodothyronine 5 deiodinas(EC 3.8.1.4) activity in BAT peaked at birth, as did hepatic iodothyronine Sdeiodinase activity and was significantly greater in lambs born to under-fed shorn ewes, which exhibited a higher plasma triiodothyronine concentration. Chronic maternal adaptations to prolonged cold exposure appear to enable pregnant ewes to compensate for the negative effects of under-feeding on fetal growth and development

scholarly journals Evidence for unmasking of rat brown-adipose-tissue mitochondrial GDP-binding sites in response to acute cold exposure. Effects of washing with albumin on GDP binding

1986 ◽  
Vol 233 (3) ◽  
pp. 743-747 ◽  
Author(s):  
C L Gribskov ◽  
M F Henningfield ◽  
A G Swick ◽  
R W Swick
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Binding Sites ◽  
Uncoupling Protein ◽  
Fold Increase ◽  
Scatchard Analysis ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

Rats, previously acclimated to 29 degrees C, were moved into the cold (4 degrees C) for 2 h. Scatchard analysis of GDP binding to the brown-adipose-tissue mitochondria of these animals showed a 2.3-fold increase in the number of high-affinity sites and a 1.5-fold increase in the number of low-affinity sites compared with binding in animals maintained at 29 degrees C. Immunochemical determination showed no increase in the amount of mitochondrial uncoupling protein during this period. This strongly suggests an unmasking of existing GDP-binding sites before a detectable increase in synthesis of uncoupling protein can occur. Washing with albumin increased the number of GDP-binding sites of brown-adipose-tissue mitochondria from both warm-housed and cold-exposed animals to the same extent. This indicates that the effects of washing with albumin and cold exposure are independent and additive.

Thyroxine 5'-deiodinase in brown adipose tissue of myopathic hamsters

1986 ◽  
Vol 251 (1) ◽  
pp. E8-E13 ◽  
Author(s):  
J. Kopecky ◽  
L. Sigurdson ◽  
I. R. Park ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Uncoupling Protein ◽  
High Fat ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Endogenous Production ◽  
Deiodinase Activity ◽  
Brown Adipose

Myopathic Syrian hamsters (BIO 14.6) have less brown adipose tissue (BAT) than normal. The trophic response of this tissue to cold is smaller than normal and trophic responses to diet and to photoperiod are absent. The objective was to find out whether activity of thyroxine 5'-deiodinase in their BAT was increased normally in response to cold and thus whether a defect in endogenous production of 3,5,3'-triiodothyronine might underlie the attenuated trophic response. The effect of feeding a high-fat diet on activity of 5'-deiodinase was also studied. Cold acclimation increased thyroxine 5'-deiodinase activity in BAT of the myopathic hamster, but the total remained smaller than normal because of the smaller size. The cold-induced increase in concentration of mitochondrial uncoupling protein was also smaller than normal. The level of serum 3,5,3'-triiodothyronine was low in myopathic hamsters and remained lower than normal when they were cold-exposed or cold acclimated. Feeding the high-fat diet to myopathic hamsters resulted in a greater than normal suppression of thyroxine 5'-deiodinase activity than in normal hamsters; the normal increases in protein content and in concentration of mitochondrial uncoupling protein were absent. We conclude that the defective trophic response of BAT of the myopathic hamster is not secondary to defective regulation of its thyroxine 5'-deiodinase activity because this activity does not appear to be obligatorily linked to hypertrophy of BAT. The low level of serum 3,5,3'-triiodothyronine in the myopathic hamster may be secondary to reduced capacity for peripheral thyroxine deiodination in its BAT.

scholarly journals PACAP is essential for the adaptive thermogenic response of brown adipose tissue to cold exposure

2014 ◽  
Vol 222 (3) ◽  
pp. 327-339 ◽  
Author(s):  
Abdoulaye Diané ◽  
Nikolina Nikolic ◽  
Alexander P Rudecki ◽  
Shannon M King ◽  
Drew J Bowie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Metabolic Rate ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Morphological Properties ◽  
Brown Adipose ◽  
Thermogenic Response

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widely distributed neuropeptide that acts as a neurotransmitter, neuromodulator, neurotropic factor, neuroprotectant, secretagogue,and neurohormone. Owing to its pleiotropic biological actions, knockout ofPacap(Adcyap1) has been shown to induce several abnormalities in mice such as impaired thermoregulation. However, the underlying physiological and molecular mechanisms remain unclear. A previous report has shown that cold-exposedPacapnull mice cannot supply appropriate levels of norepinephrine (NE) to brown adipocytes. Therefore, we hypothesized that exogenous NE would rescue the impaired thermogenic response ofPacapnull mice during cold exposure. We compared the adaptive thermogenic capacity ofPacap−/−toPacap+/+mice in response to NE when housed at room temperature (24 °C) and after a 3.5-week cold exposure (4 °C). Biochemical parameters, expression of thermogenic genes, and morphological properties of brown adipose tissue (BAT) and white adipose tissue (WAT) were also characterized. Results showed that there was a significant effect of temperature, but no effect of genotype, on the resting metabolic rate in conscious, unrestrained mice. However, the normal cold-induced increase in the basal metabolic rate and NE-induced increase in thermogenesis were severely blunted in cold-exposedPacap−/−mice. These changes were associated with altered substrate utilization, reduced β3-adrenergic receptor (β3-Ar(Adrb3)) and hormone-sensitive lipase (Hsl(Lipe)) gene expression, and increased fibroblast growth factor 2 (Fgf2) gene expression in BAT. Interestingly,Pacap−/−mice had depleted WAT depots, associated with upregulated uncoupling protein 1 expression in inguinal WATs. These results suggest that the impairment of adaptive thermogenesis inPacapnull mice cannot be rescued by exogenous NE perhaps in part due to decreased β3-Ar-mediated BAT activation.

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 Regulation of GDP binding and uncoupling-protein concentration in brown-adipose-tissue mitochondria. The effects of cold-acclimation, warm-reacclimation and noradrenaline

1988 ◽  
Vol 249 (2) ◽  
pp. 451-457 ◽  
Author(s):  
T Peachey ◽  
R R French ◽  
D A York
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Protein Concentration ◽  
Uncoupling Protein ◽  
Potassium Acetate ◽  
Zucker Rats ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Acute Response ◽  
Brown Adipose

We have used a specific immunoassay for uncoupling protein and [3H]GDP binding to study the acute and chronic responses of brown-adipose-tissue (BAT) mitochondria of warm-acclimated rats to housing at 4 degrees C and cold-acclimated rats to housing at 27 degrees C. These studies have shown the following. (1) In the cold-exposed rat the increase in mitochondrial uncoupling-protein concentration parallels the increase in GDP binding from 1 day to 5 days, but that acutely (initial 4 h) the increase in GDP binding is not associated with any change in uncoupling-protein concentration. 2. In the cold-acclimated rat rehoused at 27 degrees C, GDP binding fell by over 50% in the first 2 days, without any change in uncoupling-protein concentrations. 3. Noradrenaline acutely (30 min) increased BAT mitochondrial GDP binding of lean and obese Zucker rats, without any change in uncoupling-protein concentrations. 4. The increases in GDP binding in cold-exposed rats were associated with increases in the rate of swelling of mitochondria in the presence of valinomycin and potassium acetate. The evidence supports the hypothesis that the acute response of the rat to changes in environmental temperature are associated with unmasking or remasking of uncoupling protein, whereas chronically changes in uncoupling-protein concentration predominate.

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