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

1990 ◽  
Vol 258 (1) ◽  
pp. R51-R56 ◽  
Author(s):  
E. Chan ◽  
R. Swaminathan

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.

1988 ◽  
Vol 255 (6) ◽  
pp. R874-R881 ◽  
Author(s):  
I. R. Park ◽  
J. Himms-Hagen

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.


Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 904 ◽  
Author(s):  
Linjie Wang ◽  
Xin Yang ◽  
Yuehua Zhu ◽  
Siyuan Zhan ◽  
Zhe Chao ◽  
...  

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.


1989 ◽  
Vol 257 (1) ◽  
pp. E81-E87 ◽  
Author(s):  
I. R. Park ◽  
D. B. Mount ◽  
J. Himms-Hagen

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.


1990 ◽  
Vol 68 (6) ◽  
pp. 973-979 ◽  
Author(s):  
Rachel E. Milner ◽  
Paul Trayhurn

A dot immunobinding ("dot blot") method for measuring uncoupling protein in brown adipose tissue mitochondria is described. Mitochondrial proteins were solubilized in sodium dodecyl sulfate and applied directly to a nitrocellulose membrane housed in a 96-well microfiltration manifold. Spare binding sites on the nitrocellulose membrane were blocked with bovine serum albumin and then anti-(uncoupling protein) serum was applied. The antigen–antibody complex was detected by the addition of 125I-labelled protein A. Each nitrocellulose "dot" was cut out and its radioactivity was counted. A calibration curve was constructed from purified uncoupling protein standards, taken through the entire procedure. The dot immunobinding method is sensitive (nanogram quantities of uncoupling protein), and in contrast to conventional radioimmunoassay and enzyme-linked immunosorbent assay procedures, it is also rapid and appears to be very robust. The method has been successfully applied to the measurement of uncoupling protein in brown adipose tissue mitochondria of Richardson's ground squirrel, rats, and mice.Key words: brown adipose tissue, uncoupling protein, dot immunobinding, immunoassay, thermogenesis.


2021 ◽  
Vol 15 ◽  
Author(s):  
Lachlan Van Schaik ◽  
Christine Kettle ◽  
Rodney Green ◽  
Helen R. Irving ◽  
Joseph A. Rathner

The impact of brown adipose tissue (BAT) metabolism on understanding energy balance in humans is a relatively new and exciting field of research. The pathogenesis of obesity can be largely explained by an imbalance between caloric intake and energy expenditure, but the underlying mechanisms are far more complex. Traditional non-selective sympathetic activators have been used to artificially elevate energy utilization, or suppress appetite, however undesirable side effects are apparent with the use of these pharmacological interventions. Understanding the role of BAT, in relation to human energy homeostasis has the potential to dramatically offset the energy imbalance associated with obesity. This review discusses paradoxical effects of caffeine on peripheral adenosine receptors and the possible role of adenosine in increasing metabolism is highlighted, with consideration to the potential of central rather than peripheral mechanisms for caffeine mediated BAT thermogenesis and energy expenditure. Research on the complex physiology of adipose tissue, the embryonic lineage and function of the different types of adipocytes is summarized. In addition, the effect of BAT on overall human metabolism and the extent of the associated increase in energy expenditure are discussed. The controversy surrounding the primary β-adrenoceptor involved in human BAT activation is examined, and suggestions as to the lack of translational findings from animal to human physiology and human in vitro to in vivo models are provided. This review compares and distinguishes human and rodent BAT effects, thus developing an understanding of human BAT thermogenesis to aid lifestyle interventions targeting obesity and metabolic syndrome. The focus of this review is on the effect of BAT thermogenesis on overall metabolism, and the potential therapeutic effects of caffeine in increasing metabolism via its effects on BAT.


Author(s):  
Michael L. Blackburn ◽  
Umesh D Wankhade ◽  
Kikumi D Ono-Moore ◽  
Sree V Chintapalli ◽  
Renee Fox ◽  
...  

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.


2012 ◽  
Vol 302 (2) ◽  
pp. C463-C472 ◽  
Author(s):  
Joo-Young Lee ◽  
Nobuyuki Takahashi ◽  
Midori Yasubuchi ◽  
Young-Il Kim ◽  
Hikari Hashizaki ◽  
...  

Uncoupling protein (UCP)-1 expressed in brown adipose tissue plays an important role in thermogenesis. Recent data suggest that brown-like adipocytes in white adipose tissue (WAT) and skeletal muscle play a crucial role in the regulation of body weight. Understanding of the mechanism underlying the increase in UCP-1 expression level in these organs should, therefore, provide an approach to managing obesity. The thyroid hormone (TH) has profound effects on mitochondrial biogenesis and promotes the mRNA expression of UCP in skeletal muscle and brown adipose tissue. However, the action of TH on the induction of brown-like adipocytes in WAT has not been elucidated. Thus we investigate whether TH could regulate UCP-1 expression in WAT using multipotent cells isolated from human adipose tissue. In this study, triiodothyronine (T3) treatment induced UCP-1 expression and mitochondrial biogenesis, accompanied by the induction of the CCAAT/enhancer binding protein, peroxisome proliferator-activated receptor-γ coactivator-1α, and nuclear respiratory factor-1 in differentiated human multipotent adipose-derived stem cells. The effects of T3 on UCP-1 induction were dependent on TH receptor-β. Moreover, T3 treatment increased oxygen consumption rate. These findings indicate that T3 is an active modulator, which induces energy utilization in white adipocytes through the regulation of UCP-1 expression and mitochondrial biogenesis. Our findings provide evidence that T3 serves as a bipotential mediator of mitochondrial biogenesis.


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