Iodothyronine 5′-deiodinase activity as an early event of prenatal brown-fat differentiation in bovine development

Iodothyronine 5'-deiodinase activity appears to be a type I enzyme in bovine brown adipose tissue, on the basis of its high Km for 3,3',5'-tri-iodothyronine (‘reverse T3’) (in the micromolar range) and sensitivity to propylthiouracil inhibition. This enzyme activity is already detectable in perirenal adipose tissue of bovine fetuses in the second month of gestation, reaches peak values around the seventh month of fetal life, declines before birth, becomes lower after parturition and finally undetectable in the adult cow. Iodothyronine 5'-deiodinase activity is present in the pericardic, peritoneal and intermuscular adipose depots of the neonatal calf, but it is always undetectable in the subcutaneous adipose tissue. It is concluded that iodothyronine 5'-deiodinase is a specific feature of brown fat in the bovine species that is not shared by white adipose tissue. white adipose tissue. Peak values of 5'-deiodinating activity appear as an early event in the prenatal differentiation programme of bovine brown-fat cells as they occur when uncoupling-protein-gene expression first starts.

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CCAAT/enhancer-binding proteins α and β in brown adipose tissue: evidence for a tissue-specific pattern of expression during development

Biochemical Journal ◽

10.1042/bj3020695 ◽

1994 ◽

Vol 302 (3) ◽

pp. 695-700 ◽

Cited By ~ 27

Author(s):

C Manchado ◽

P Yubero ◽

O Viñas ◽

R Iglesias ◽

F Villarroya ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Brown Fat ◽

Brown Adipocyte ◽

Fetal Life ◽

Inhibitory Protein ◽

Adult Rats ◽

Stage Of Development ◽

Brown Adipose

CCAAT/enhancer-binding protein (C/EBP) alpha mRNA and its protein products C/EBP alpha and 30 kDa C/EBP alpha are expressed in rat brown-adipose tissue. Results also demonstrate the expression of C/EBP beta mRNA and its protein products C/EBP beta and liver inhibitory protein (LIP) in the tissue. The abundance of C/EBP alpha and C/EBP beta proteins in adult brown fat is similar to that found in adult liver. However, the expression of C/EBP alpha and C/EBP beta is specifically regulated in brown fat during development. C/EBP alpha, 30 kDa C/EBP alpha, C/EBP beta and LIP content is several-fold higher in fetal brown fat than in the adult tissue, or liver at any stage of development. Peak values are attained in late fetal life, in concurrence with the onset of transcription of the uncoupling protein (UCP) gene, the molecular marker of terminal brown-adipocyte differentiation. When adult rats are exposed to a cold environment, which is a physiological stimulus of brown-adipose tissue hyperplasia and UCP gene expression, a specific rise in C/EBP beta expression with respect to C/EBP alpha, 30 kDa C/EBP alpha and LIP is observed. Present data suggest that the C/EBP family of transcription factors has an important role in the development and terminal differentiation of brown-adipose tissue.

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Brown Adipose Tissue Growth and Development

Scientifica ◽

10.1155/2013/305763 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 44

Author(s):

Michael E. Symonds

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Tissue Growth ◽

Brown Fat ◽

Prevention Strategies ◽

Brown Adipose ◽

Beige Adipocytes ◽

Substantial Rise

Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.1.e8 ◽

1986 ◽

Vol 251 (1) ◽

pp. E8-E13 ◽

Cited By ~ 1

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.

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Central stimulatory effect of leptin on T3production is mediated by brown adipose tissue type II deiodinase

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00196.2002 ◽

2002 ◽

Vol 283 (5) ◽

pp. E980-E987 ◽

Cited By ~ 31

Author(s):

Philippe Cettour-Rose ◽

Albert G. Burger ◽

Christoph A. Meier ◽

Theo J. Visser ◽

Françoise Rohner-Jeanrenaud

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Mrna Expression ◽

Uncoupling Protein ◽

Tissue Type ◽

Type I ◽

Type Ii ◽

Brown Adipose ◽

Small Doses ◽

Food Consumed

To assess whether intracerebroventricular leptin administration affects monodeiodinase type II (D2) activity in the tissues where it is expressed [cerebral cortex, hypothalamus, pituitary, and brown adipose tissue (BAT)], hepatic monodeiodinase type I (D1) activity was inhibited with propylthiouracil (PTU), and small doses of thyroxine (T4; 0.6 nmol · 100 g body wt−1 · day−1) were supplemented to compensate for the PTU-induced hypothyroidism. Two groups of rats were infused with leptin for 6 days, one of them being additionally treated with reverse triiodothyronine (rT3), an inhibitor of D2. Control rats were infused with vehicle and pair-fed the amount of food consumed by leptin-infused animals. Central leptin administration produced marked increases in D2 mRNA expression and activity in BAT, changes that were likely responsible for increased plasma T3 and decreased plasma T4 levels. Indeed, plasma T3 and T4 concentrations were unaltered by central leptin administration in the presence of rT3. The additional observation of a leptin-induced increased mRNA expression of BAT uncoupling protein-1 suggested that the effect on BAT D2 may be mediated by the sympathetic nervous system.

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Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1519358112 ◽

2015 ◽

Vol 112 (45) ◽

pp. 14006-14011 ◽

Cited By ~ 22

Author(s):

Yifei Miao ◽

Wanfu Wu ◽

Yubing Dai ◽

Laure Maneix ◽

Bo Huang ◽

...

Keyword(s):

Adipose Tissue ◽

Thyroid Hormone ◽

Energy Expenditure ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Thyroid Stimulating Hormone ◽

Vital Role ◽

Normal Diet ◽

Subcutaneous White Adipose Tissue ◽

Brown Adipose

The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

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Current Progress in Adipose Tissue Biology: Implications in Obesity and Its Comorbidities

The Indonesian Biomedical Journal ◽

10.18585/inabj.v12i2.1171 ◽

2020 ◽

Vol 12 (2) ◽

pp. 85-101

Author(s):

Anna Meiliana ◽

Nurrani Mustika Dewi ◽

Andi Wijaya

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Common Factor ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Protein Levels ◽

Brown Adipose ◽

Key Factor ◽

Beige Fat

BACKGROUND: Obesity has been decades become a highly interest study, accompanied by the realization that adipose tissue (AT) plays a major role in the regulation of metabolic function.CONTENT: In past few years, adipocytes classification, development, and differentiation has been significant changes. The white adipose tissue (WAT) can transform to a phenotype like brown adipose (BAT) type and function. Exercise and cold induction were the most common factor for fat browning; however batokines such as fibroblast growth factor (FGF)-21, interleukin (IL)-6, Slit homolog 2 protein (SLIT2)-C, and Meteorin-like protein (METRNL) perform a beneficial browning action by increasing peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α protein levels, a key factor to stimulate mitochondrial biogenesis and uncoupling Protein 1 (UCP1) transcription, thus change the WAT phenotype into beige.SUMMARY: AT recently known as a complex organ, not only bearing a storage function but as well as the master regulator of energy balance and nutritional homeostasis; brown and beige fat express constitutively high levels of thermogenic genes and raise our expectation on new strategies for fighting obesity and metabolic disorders.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, inflammation, IR, metabolic disease

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Mutation yellow in agouti loci prevents age-related increase of skeletal muscle genes regulating free fatty acids oxidation

Vavilov Journal of Genetics and Breeding ◽

10.18699/vj18.358 ◽

2018 ◽

Vol 22 (2) ◽

pp. 265-272 ◽

Cited By ~ 1

Author(s):

Y. V. Piskunova ◽

A. Y. Kazantceva ◽

A. V. Baklanov ◽

N. M. Bazhan

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Adipose Tissue ◽

Free Fatty Acids ◽

Glucose Uptake ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Age Related ◽

Brown Adipose ◽

Ay Mice

The lethal yellow mutation in agouti loci (Ay mutation) reduces the activity of melanocortin (MC) receptors and causes hyperphagia, obesity and type two diabetes mellitus in aging mice (Ay mice). It is unknown if changes in distinct elements of the metabolic system such as white adipose tissue (WAT) and brown adipose tissue (BAT), and skeletal muscle will manifest before the development of obesity. The aim of this work was to measure the relative gene expression of key proteins that regulate carbohydrate-lipid metabolism in WAT, BAT and skeletal muscle in Ay mice before the development of obesity. C57Bl/6J mice bearing a dominant autosomal mutation Ay (Ay /a mice) and mice of the standard genotype (a/a mice, control) have been studied in three age groups: 10, 15 and 30 weeks. The relative mRNA level of genes was measured by real-time PCR in skeletal muscles (uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) (free fatty acids oxidation), solute carrier family 2 (facilitated glucose transporter), member 4 (Slc2a4) (glucose uptake)), in WAT lipoprotein lipase (Lpl) (triglyceride deposition), hormone-sensitive lipase (Lipe) (lipid mobilization), and Slc2a4 (glucose uptake)), and in BAT: uncoupling protein 1 (Ucp1) (energy expenditure). The expression of Cpt1b was reduced in young Ay mice (10 weeks), there was no transient peak of transcription of Cpt1b, Ucp3 in skeletal muscle tissue and Lipe, Slc2a4 in WAT in early adult Ay mice (15 weeks), which was noted in а/а mice. Reduction of the transcriptional activity of the studied genes in skeletal muscle and white adipose tissue can initiate the development of melanocortin obesity in Ay mice.

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

Cells ◽

10.3390/cells8080904 ◽

2019 ◽

Vol 8 (8) ◽

pp. 904 ◽

Cited By ~ 2

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.

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CD137 negatively affects “browning” of white adipose tissue during cold exposure

Journal of Biological Chemistry ◽

10.1074/jbc.ac119.011795 ◽

2020 ◽

Vol 295 (7) ◽

pp. 2034-2042 ◽

Cited By ~ 2

Author(s):

Raj Kamal Srivastava ◽

Annalena Moliner ◽

Ee-Soo Lee ◽

Emily Nickles ◽

Eunice Sim ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Cold Exposure ◽

Uncoupling Protein ◽

Surface Protein ◽

Negative Regulator ◽

Subcutaneous White Adipose Tissue ◽

Brown Adipose ◽

Beige Adipocytes ◽

A Cell

Prolonged cold exposure stimulates the formation of brownlike adipocytes expressing UCP1 (uncoupling-protein-1) in subcutaneous white adipose tissue which, together with classical brown adipose tissue, contributes to maintaining body temperature in mammals through nonshivering thermogenesis. The mechanisms that regulate the formation of these cells, alternatively called beige or brite adipocytes, are incompletely understood. Here we report that mice lacking CD137, a cell surface protein used in several studies as a marker for beige adipocytes, showed elevated levels of thermogenic markers, including UCP1, increased numbers of beige adipocyte precursors, and expanded UCP1-expressing cell clusters in inguinal white adipose tissue after chronic cold exposure. CD137 knockout mice also showed enhanced cold resistance. These results indicate that CD137 functions as a negative regulator of “browning” in white adipose tissue and call into question the use of this protein as a functional marker for beige adipocytes.

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Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization

Journal of Cell Science ◽

10.1242/jcs.103.4.931 ◽

1992 ◽

Vol 103 (4) ◽

pp. 931-942 ◽

Cited By ~ 4

Author(s):

B. Cousin ◽

S. Cinti ◽

M. Morroni ◽

S. Raimbault ◽

D. Ricquier ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Blot Hybridization ◽

Morphological Characterization ◽

Northern Blot Hybridization ◽

Mitochondrial Uncoupling ◽

Brown Adipocytes ◽

Morphological Studies ◽

Brown Adipose

Brown adipocytes are thermogenic cells which play an important role in energy balance. Their thermogenic activity is due to the presence of a mitochondrial uncoupling protein (UCP). Until recently, it was admitted that in rodents brown adipocytes were mainly located in classical brown adipose tissue (BAT). In the present study, we have investigated the presence of UCP protein or mRNA in white adipose tissue (WAT) of rats. Using polymerase chain reaction or Northern blot hybridization, UCP mRNA was detected in mesenteric, epidydimal, retroperitoneal, inguinal and particularly in periovarian adipose depots. The uncoupling protein was detected by Western blotting in mitochondria from periovarian adipose tissue. When rats were submitted to cold or to treatment with a beta-adrenoceptor agonist, UCP expression was increased in this tissue as in typical brown fat. Moreover, the expression was decreased in obese fa/fa rats compared to lean controls. Morphological studies showed that periovarian adipose tissue of rats kept at 24 degrees C contained cells with numerous typical BAT mitochondria with or without multilocular lipid droplets. Immunocytochemistry confirmed that multilocular cells expressed mitochondrial UCP. Furthermore, the number of brown adipocytes and the density of mitochondrial cristae increased in parallel with exposure to cold. These results demonstrate that adipocytes expressing UCP are present in adipose deposits considered as white fat. They suggest the existence of a continuum in rodents between BAT and WAT, and a great plasticity between adipose tissue phenotypes. The physiological importance of brown adipocytes in WAT and the regulation of UCP expression remain open questions.

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