Comparative Transcriptome Profiling of Young and Old Brown Adipose Tissue Thermogenesis

Brown adipose tissue (BAT) is a major site for uncoupling protein 1 (UCP1)-mediated non-shivering thermogenesis. BAT dissipates energy via heat generation to maintain the optimal body temperature and increases energy expenditure. These energetic processes in BAT use large amounts of glucose and fatty acid. Therefore, the thermogenesis of BAT may be harnessed to treat obesity and related diseases. In mice and humans, BAT levels decrease with aging, and the underlying mechanism is elusive. Here, we compared the transcriptomic profiles of both young and aged BAT in response to thermogenic stimuli. The profiles were extracted from the GEO database. Intriguingly, aging does not cause transcriptional changes in thermogenic genes but upregulates several pathways related to the immune response and downregulates metabolic pathways. Acute severe CE upregulates several pathways related to protein folding. Chronic mild CE upregulates metabolic pathways, especially related to carbohydrate metabolism. Our findings provide a better understanding of the effects of aging and metabolic responses to thermogenic stimuli in BAT at the transcriptome level.

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Alternative Polyadenylation and Differential Regulation of Ucp1: Implications for Brown Adipose Tissue Thermogenesis Across Species

Frontiers in Pediatrics ◽

10.3389/fped.2020.612279 ◽

2021 ◽

Vol 8 ◽

Author(s):

Wen-Hsin Lu ◽

Yao-Ming Chang ◽

Yi-Shuian Huang

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Molecular Mechanisms ◽

Uncoupling Protein ◽

Alternative Polyadenylation ◽

Proton Channel ◽

Inner Mitochondrial Membrane ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Ucp1 Expression

Brown adipose tissue (BAT) is a thermogenic organ owing to its unique expression of uncoupling protein 1 (UCP1), which is a proton channel in the inner mitochondrial membrane used to dissipate the proton gradient and uncouple the electron transport chain to generate heat instead of adenosine triphosphate. The discovery of metabolically active BAT in human adults, especially in lean people after cold exposure, has provoked the “thermogenic anti-obesity” idea to battle weight gain. Because BAT can expend energy through UCP1-mediated thermogenesis, the molecular mechanisms regulating UCP1 expression have been extensively investigated at both transcriptional and posttranscriptional levels. Of note, the 3′-untranslated region (3′-UTR) of Ucp1 mRNA is differentially processed between mice and humans that quantitatively affects UCP1 synthesis and thermogenesis. Here, we summarize the regulatory mechanisms underlying UCP1 expression, report the number of poly(A) signals identified or predicted in Ucp1 genes across species, and discuss the potential and caution in targeting UCP1 for enhancing thermogenesis and metabolic fitness.

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Thyroid hormones in the regulation of brown adipose tissue thermogenesis

Endocrine Connections ◽

10.1530/ec-20-0562 ◽

2021 ◽

Author(s):

Sarah Christine Sentis ◽

Rebecca Oelkrug ◽

Jens Mittag

Keyword(s):

Adipose Tissue ◽

Thyroid Hormone ◽

Brown Adipose Tissue ◽

Heat Loss ◽

Current Knowledge ◽

Uncoupling Protein ◽

Sympathetic Stimulation ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Key Aspects

A normal thyroid status is crucial for body temperature homeostasis, as thyroid hormone regulates both heat loss and conservation as well as heat production in thermogenic tissues. Brown adipose tissue (BAT) is the major site of non-shivering thermogenesis and an important target of thyroid hormone action. Thyroid hormone not only regulates the tissue’s sensitivity to sympathetic stimulation by norepinephrine, but also the expression of uncoupling protein 1, the key driver of BAT thermogenesis. Vice versa, sympathetic stimulation of BAT triggers the expression of deiodinase type II, an enzyme that enhances local thyroid hormone availability and signaling. This review summarizes the current knowledge on how thyroid hormone controls BAT thermogenesis, aiming to dissect the direct actions of the hormone in BAT and its indirect actions via the central nervous system, browning of white adipose tissue or heat loss over body surfaces. Of particular relevance is the apparent dose dependency of the observed effects, as we find that minor or moderate changes in thyroid hormone levels often have different effects as compared to high pharmacological doses. Moreover, we conclude that the more recent findings require a reevaluation of older studies, as key aspects such as heat loss or central BAT activation may not have received the necessary attention during the interpretation of these early findings. Finally, we provide a list of what we believe are the most relevant questions in the field that to date are still enigmatic and require further studies.

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Ethanol and Brown Adipose Tissue Thermogenesis in Rats Exposed to the Cold: Uncoupling Protein m-RNA

Thermal Balance in Health and Disease ◽

10.1007/978-3-0348-7429-8_17 ◽

1994 ◽

pp. 129-131

Author(s):

P. Huttunen ◽

M. Sämpi ◽

R. Myllylä

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

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Thermogenic activity and capacity of brown fat in fasted and refed golden hamsters

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.252.5.r987 ◽

1987 ◽

Vol 252 (5) ◽

pp. R987-R993 ◽

Cited By ~ 3

Author(s):

I. Levin ◽

P. Trayhurn

Keyword(s):

Adipose Tissue ◽

Cytochrome C ◽

Brown Adipose Tissue ◽

Cytochrome C Oxidase ◽

Golden Hamster ◽

Oxidase Activity ◽

Uncoupling Protein ◽

Mitochondrial Mass ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

The effects of different food deprivation regimens on the thermogenic activity and capacity of brown adipose tissue in the golden hamster have been investigated. Thermogenesis in the tissue was assessed by measurements of tissue cytochrome-c oxidase activity, mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein. The thermogenic activity and capacity of brown adipose tissue were found to be markedly reduced in fasted or underweight hamsters. Measurements of cytochrome-c oxidase activity indicate that the reductions were caused exclusively by a loss in mitochondrial mass, uncoupling protein concentration and GDP binding to mitochondria remaining unchanged. The decrease in brown adipose tissue thermogenesis was associated with a reduction in the capacity for nonshivering thermogenesis in the whole animal. Hamsters recovered from weight losses without increasing their food intake, and the recovery was accompanied by a normalization in mitochondrial mass in brown adipose tissue. Mitochondrial mass was, however, restored only after 10 days of ad libitum refeeding. These results suggest that the reduction in energy expenditure in the fasted hamster could relate to a decrease in brown adipose tissue thermogenesis, in addition to the previously reported decreases in resting metabolic rate and locomotor activity. Reductions in thermogenesis may also represent a further mechanism by which energy stores recover in the golden hamster without postfast hyperphagia.

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A commentary on the interpretation of in vitro biochemical measures of brown adipose tissue thermogenesis

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-128 ◽

1989 ◽

Vol 67 (8) ◽

pp. 811-819 ◽

Cited By ~ 54

Author(s):

Paul Trayhurn ◽

Rachel E. Milner

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Binding Sites ◽

Protein Concentration ◽

Uncoupling Protein ◽

Proton Conductance ◽

Binding Studies ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

In this article we comment on the various in vitro biochemical measurements employed to assess the thermogenic activity and capacity of brown adipose tissue. The meaning and significance of changes in tissue weight, protein content, cell number, and mitochondrial mass are each summarized. In addition, various indices of the proton conductance pathway – mitochondrial swelling, proton conductance, uncoupling protein concentration, and GDP binding studies – are discussed. The issue of unmasking and masking of GDP binding sites is reviewed; recent reports have clearly demonstrated unmasking and masking, and it is concluded that GDP binding studies are an index of the activity of uncoupling protein, rather than a measure of its concentration. It is suggested that tissue mass, mitochondrial content, mitochondrial GDP binding, and uncoupling protein concentration represent core measurements for the biochemical assessment of the thermogenic activity and capacity of brown adipose tissue. Auxiliary measurements include Scatchard analysis of GDP binding data to distinguish changes in the number of binding sites from potential changes in Kd, and mitochondrial swelling studies, as an additional index of proton permeability. The distinction between thermogenic activity (GDP binding, proton permeability) and capacity (uncoupling protein content), both on a per unit of mitochondrial protein and per tissue basis, is emphasized.Key words: brown adipose tissue, thermogenesis, uncoupling protein, mitochondria.

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Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice

Nutrients ◽

10.3390/nu13082499 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2499

Author(s):

Annett Hoffmann ◽

Thomas Ebert ◽

Mohammed K. Hankir ◽

Gesine Flehmig ◽

Nora Klöting ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Regulatory Element ◽

Subcutaneous Administration ◽

Sympathetic Nerves ◽

Metabolic Dysfunction ◽

Brown Adipose ◽

Element Binding Protein ◽

Brown Adipose Tissue Thermogenesis

Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the dysregulation of several key adipokines, including leptin. Treatment with leptin or its analogues is therefore sufficient to reverse some of the metabolic symptoms of LD in patients and in mouse models through distinct mechanisms. Brown adipose tissue (BAT) thermogenesis has emerged as an important regulator of systemic metabolism in rodents and in humans, but it is poorly understood how leptin impacts BAT in LD. Here, we show in transgenic C57Bl/6 mice overexpressing sterol regulatory element-binding protein 1c in adipose tissue (Tg (aP2-nSREBP1c)), an established model of congenital LD, that daily subcutaneous administration of 3 mg/kg leptin for 6 to 8 weeks increases body temperature without affecting food intake or body weight. This is associated with increased protein expression of the thermogenic molecule uncoupling protein 1 (UCP1) and the sympathetic nerve marker tyrosine hydroxylase (TH) in BAT. These findings suggest that leptin treatment in LD stimulates BAT thermogenesis through sympathetic nerves, which might contribute to some of its metabolic benefits by providing a healthy reservoir for excess circulating nutrients.

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