Role of T3 in thermogenic and trophic responses of brown adipose tissue to cold

1989 ◽  
Vol 257 (1) ◽  
pp. E81-E87 ◽  
Author(s):  
I. R. Park ◽  
D. B. Mount ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Optimal Growth ◽  
Endogenous Production ◽  
Brown Adipose ◽  
Trophic Responses ◽  
Optimal Growth Rate

Cold-induced growth of brown adipose tissue (BAT) was studied in thyroidectomized rats that received low doses of either thyroxine (T4) or 3,5,3'-triidothyronine (T3). The objective was to find out whether the cold-induced increase in activity of T4 5'-deiodinase, and thus increased endogenous T3 generation in BAT itself, was necessary for growth of BAT or whether T3 from the blood could serve as effectively as T3 produced endogenously. The acute thermogenic response of BAT to cold (15 h at 4 degrees C), as measured by the increase in mitochondrial GDP binding, was abolished by thyroidectomy, as seen previously, and restored by T3 as well as by T4 treatment. The long-term trophic response to cold (20–25 days at 4 degrees C), as indicated by increases in protein and DNA and in mitochondrial concentrations of GDP-binding sites and uncoupling protein, occurred whether T3 or T4 was administered to these thyroidectomized rats. We conclude that endogenous T3 production in BAT does not direct and is not essential for the long-term trophic response of this tissue to cold. We are not able to exclude, on the basis of the present results, that an optimal growth rate during the initial phase of the trophic response may require enhanced endogenous production of T3 in BAT. The cold-induced increase in T4 5'-deiodinase activity, presumably mediated by an action of norepinephrine, does not require the presence of either T3 or T4, as seen previously by others.

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.

Neural influences on trophic changes in brown adipose tissue during cold acclimation

1988 ◽  
Vol 255 (6) ◽  
pp. R874-R881 ◽  
Author(s):  
I. R. Park ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Acclimation ◽  
Elevated Level ◽  
Uncoupling Protein ◽  
Sympathetic Innervation ◽  
Intact Tissue ◽  
Brown Adipose ◽  
Neural Influences

We studied the role of the sympathetic innervation in development and maintenance of increased levels of uncoupling protein (UCP) and of thyroxine 5'-deiodinase (TD) during cold-induced growth of brown adipose tissue (BAT). Interscapular BAT was unilaterally (and in some experiments, bilaterally) denervated either before acclimation to cold (4 degrees C) for 12 days or after 14 days of a total 28-day period of acclimation to cold. BAT norepinephrine was reduced to 3-7% of the normal level in denervated BAT for up to 26 days. Denervation slowed, but did not prevent, cold-induced increases in total protein, in mitochondrial GDP binding, and in mitochondrial UCP concentration, which all reached 50% or more of the elevated level in intact tissue. In contrast, TD activity did not exceed 10% of the elevated level in intact tissue at any time. Denervation after cold acclimation resulted in a very rapid loss of TD activity, a slower and selective loss (after a lag of 1 day) of UCP, and a much slower loss of tissue protein. We conclude that the sympathetic innervation is required for an optimal trophic response of BAT to cold acclimation and for maintenance in the hypertrophied state but that other factors are also involved. Induction and maintenance of TD in BAT does need the sympathetic innervation.

scholarly journals Genome-Wide Identification and Characterization of Long Noncoding RNAs of Brown to White Adipose Tissue Transformation in Goats

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 904 ◽  
Author(s):  
Linjie Wang ◽  
Xin Yang ◽  
Yuehua Zhu ◽  
Siyuan Zhan ◽  
Zhe Chao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Unsaturated Fatty Acids ◽  
Uncoupling Protein ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Brown Adipose ◽  
Perirenal Fat

Long noncoding RNAs (lncRNAs) play an important role in the thermogenesis and energy storage of brown adipose tissue (BAT). However, knowledge of the cellular transition from BAT to white adipose tissue (WAT) and the potential role of lncRNAs in goat adipose tissue remains largely unknown. In this study, we analyzed the transformation from BAT to WAT using histological and uncoupling protein 1 (UCP1) gene analyses. Brown adipose tissue mainly existed within the goat perirenal fat at 1 day and there was obviously a transition from BAT to WAT from 1 day to 1 year. The RNA libraries constructed from the perirenal adipose tissues of 1 day, 30 days, and 1 year goats were sequenced. A total number of 21,232 lncRNAs from perirenal fat were identified, including 5393 intronic-lncRNAs and 3546 antisense-lncRNAs. Furthermore, a total of 548 differentially expressed lncRNAs were detected across three stages (fold change ≥ 2.0, false discovery rate (FDR) < 0.05), and six lncRNAs were validated by qPCR. Furthermore, trans analysis found lncRNAs that were transcribed close to 890 protein-coding genes. Additionally, a coexpression network suggested that 4519 lncRNAs and 5212 mRNAs were potentially in trans-regulatory relationships (r > 0.95 or r < −0.95). In addition, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that the targeted genes were involved in the biosynthesis of unsaturated fatty acids, fatty acid elongation and metabolism, the citrate cycle, oxidative phosphorylation, the mitochondrial respiratory chain complex, and AMP-activated protein kinase (AMPK) signaling pathways. The present study provides a comprehensive catalog of lncRNAs involved in the transformation from BAT to WAT and provides insight into understanding the role of lncRNAs in goat brown adipogenesis.

Glucocorticoids and insulin: complex interaction on brown adipose tissue

1995 ◽  
Vol 268 (5) ◽  
pp. R1209-R1216 ◽  
Author(s):  
A. M. Strack ◽  
C. J. Horsley ◽  
R. J. Sebastian ◽  
S. F. Akana ◽  
M. F. Dallman
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Diabetic Rats ◽  
Insulin Effect ◽  
Caloric Efficiency ◽  
Brown Adipose ◽  
System Input ◽  
Streptozotocin Induced Diabetes

Glucocorticoids and insulin effect long-term reciprocal changes in food intake and body weight. We tested the interactions of corticosterone and insulin on caloric efficiency, white adipose tissue (WAT) stores, and brown adipose tissue (BAT). Two experiments were performed: 1) adrenalectomized rats were treated with corticosterone with or without streptozotocin-induced diabetes and 2) adrenalectomized, corticosterone-treated, diabetic rats were treated with insulin. By 4-5 days later, > or = 50% of the variance in caloric efficiency, plasma triglycerides, and WAT stores was explained by regression of these variables on corticosterone (catabolic) and insulin (anabolic). When the ratio of the hormones was normal, but concentrations high, overall gain of energy stores decreased and energy was redistributed to fat. Both hormones were anabolic on BAT lipid storage; the hormones played a complex role in the regulation of uncoupling protein (UCP) in BAT. Although corticosterone inhibited and insulin stimulated UCP, these effects were only evident in diabetics and with normoglycemia, respectively. For BAT variables, < or = 50% of the variance was explained by regression on corticosterone and insulin, suggesting that the effects of these hormones are mediated through an intermediate such as sympathetic nervous system input to BAT.

On the potential role of globins in brown adipose tissue: a novel conceptual model and studies in myoglobin knockout mice

2021 ◽  
Author(s):  
Michael L. Blackburn ◽  
Umesh D Wankhade ◽  
Kikumi D Ono-Moore ◽  
Sree V Chintapalli ◽  
Renee Fox ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Conceptual Model ◽  
Metabolic Regulation ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Sexually Dimorphic ◽  
Brown Adipose ◽  
No Signaling

Myoglobin (Mb) regulates O2 bioavailability in muscle and heart as partial pressure of O2 (pO2) drops with increased tissue workload. Globin proteins also modulate cellular NO pools, "scavenging" NO at higher pO2 and converting NO2- to NO as pO2 falls. Myoglobin binding of fatty acids may also signal a role in fat metabolism. Interestingly, Mb is expressed in brown adipose tissue (BAT), but its function is unknown. Herein, we present a new conceptual model that proposes links between BAT thermogenic activation, concurrently reduced pO2, and NO pools regulated by deoxy/oxy-globin toggling and xanthine oxidoreductase (XOR). We describe the effect of Mb knockout (Mb-/-) on BAT phenotype (lipid droplets, mitochondrial markers uncoupling protein 1 [UCP1] and cytochrome C oxidase 4 [Cox4], transcriptomics) in male and female mice fed a high fat diet (HFD, 45% of energy, ~13 wk), and examine Mb expression during brown adipocyte differentiation. Interscapular BAT weights did not differ by genotype, but there was a higher prevalence of mid-large sized droplets in Mb-/-. COX4 protein expression was significantly reduced in Mb-/- BAT, and a suite of metabolic/NO/stress/hypoxia transcripts were lower. All of these Mb-/--associated differences were most apparent in females. The new conceptual model, and results derived from Mb-/- mice, suggest a role for Mb in BAT metabolic regulation, in part through sexually dimorphic systems and NO signaling. This possibility requires further validation in light of significant mouse-to-mouse variability of BAT Mb mRNA and protein abundances in wildtype mice and lower expression relative to muscle and heart.

scholarly journals Glucagon Is Essential for Adaptive Thermogenesis in Brown Adipose Tissue

Endocrinology ◽  
2014 ◽  
Vol 155 (9) ◽  
pp. 3484-3492 ◽  
Author(s):  
Keita Kinoshita ◽  
Nobuaki Ozaki ◽  
Yusuke Takagi ◽  
Yoshiharu Murata ◽  
Yoshiharu Oshida ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Fibroblast Growth Factor 21 ◽  
Gene Encoding ◽  
Adaptive Thermogenesis ◽  
Cl 316,243 ◽  
Brown Adipose

Abstract Glucagon, a counterregulatory hormone to insulin, serves as a regulator of glucose homeostasis and acts in response to hypoglycemia. Earlier studies have shown that glucagon administration induces thermogenesis in experimental animal models. However, it is not known whether endogenous glucagon is involved in the regulation of brown adipose tissue (BAT) function. Here we investigated the role of glucagon in cold-induced thermogenesis in male mice deficient in proglucagon-derived peptides (GCGKO mice). Upon exposure to cold, GCGKO mice exhibited a greater decrease in rectal temperature than control mice. The cold exposure-induced increase in oxygen consumption in GCGKO mice was less than that seen in control mice. Moreover, the increase in oxygen consumption after administration of a β3-adrenergic receptor agonist, CL-316,243, was also lesser in GCGKO than in control mice. Expression of thermogenic genes, including the gene encoding uncoupling protein 1 (Ucp1), was reduced in the BAT of GCGKO mice under ambient as well as cold conditions. Administration of glucagon restored the expression of Ucp1 mRNA in the BAT as well as the expression of the fibroblast growth factor 21 gene (Fgf21) in the liver. Supplementation with glucagon for 2 weeks resulted in higher plasma Fgf21 levels and improved responses to CL-316,243 in GCGKO mice. These results indicated that endogenous glucagon is essential for adaptive thermogenesis and that it regulates BAT function, most likely by increasing hepatic Fgf21 production.

Role of prolactin in lactation-induced changes in brown adipose tissue

1990 ◽  
Vol 258 (1) ◽  
pp. R51-R56 ◽  
Author(s):  
E. Chan ◽  
R. Swaminathan
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Energy Utilization ◽  
Serum Prolactin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Simultaneous Administration ◽  
Brown Adipose ◽  
Induced Changes

During lactation the efficiency of energy utilization is increased and brown adipose tissue (BAT) thermogenesis is suppressed. We have examined the role of prolactin in the suppression of BAT during lactation in the rat. Changes in BAT were studied using an enzyme-linked immunosorbent assay for the uncoupling protein (UCP). In the first experiment BAT from pregnant and lactating rats was examined at various times. Total UPC content of BAT decreased from 364 +/- 34 to 32 +/- 9 micrograms during late lactation (20 days). Serum prolactin (PRL) concentration was elevated during lactation and was highest at 10 days. When endogenous PRL was stimulated by injection of metoclopramide (1.67 mg/kg) for 5 days, UCP content of BAT decreased by 50%. This action of metoclopramide could be blocked by simultaneous administration of bromocriptine, an inhibitor of PRL secretion. Serum PRL concentration was elevated during metoclopramide administration but not when metoclopramide and bromocriptine were given together. We conclude that PRL is a possible mediator of the suppression of BAT during lactation.

scholarly journals Brown fat is essential for cold-induced thermogenesis but not for obesity resistance in aP2-Ucp mice

1998 ◽  
Vol 274 (3) ◽  
pp. E527-E533 ◽  
Author(s):  
Bohumír Stefl ◽  
Alena Janovská ◽  
Zdenek Hodný ◽  
Martin Rossmeisl ◽  
Milada Horáková ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transgenic Mice ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Transgenic Animals ◽  
Brown Fat ◽  
Mitochondrial Uncoupling ◽  
Brown Adipose ◽  
Total Energy Balance

The role of brown adipose tissue in total energy balance and cold-induced thermogenesis was studied. Mice expressing mitochondrial uncoupling protein 1 (UCP-1) from the fat-specific aP2 gene promoter (heterozygous and homozygous aP2 -Ucp transgenic mice) and their nontransgenic C57BL6/J littermates were used. The transgenic animals are resistant to obesity induced by a high-fat diet, presumably due to ectopic synthesis of UCP-1 in white fat. These animals exhibited atrophy of brown adipose tissue, as indicated by smaller size of brown fat and reduction of its total UCP-1 and DNA contents. Norepinephrine-induced respiration (measured in pentobarbital sodium-anesthetized animals) was decreased proportionally to the dosage of the transgene, and the homozygous (but not heterozygous) transgenic mice exhibited a reduction in their capacity to maintain body temperature in the cold. Our results indicate that the role of brown fat in cold-induced thermogenesis cannot be substituted by increased energy expenditure in other tissues.

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