scholarly journals Vitamin D–vitamin D receptor system down-regulates expression of uncoupling proteins in brown adipocyte through interaction with Hairless protein

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Pei-qi Wang ◽  
Dao-xiang Pan ◽  
Chun-qiu Hu ◽  
Yu-lin Zhu ◽  
Xiao-jing Liu
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Vitamin D Deficiency ◽  
Vitamin D Receptor ◽  
Brown Adipocyte ◽  
Dependent Manner ◽  
Cell Nuclei ◽  
Down Regulation ◽  
Brown Adipocytes ◽  
Brown Adipose

Abstract Our previous study showed that feeding mice with vitamin D deficiency diet markedly alleviated high-fat-diet-induced overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D deficiency up-regulated the expression of uncoupling protein 3 (Ucp3) in white adipose tissue (WAT) and brown adipose tissue (BAT). The present study aimed to further investigate the effects of vitamin D and vitamin D receptor (Vdr) on Ucp1–3 (Ucps) expression in brown adipocyte and the mechanism involved in it. Rat primary brown adipocytes were separated and purified. The effects of the 1,25(OH)2D3 (1,25-dihydroxyvitamin D3; the hormonal form of vitamin D) and Vdr system on Ucps expression in brown adipocytes were investigated in basal condition and activated condition by isoproterenol (ISO) and triiodothyronine (T3). Ucps expression levels were significantly down-regulated by 1,25(OH)2D3 in the activated brown adipocyte. Vdr silencing reversed the down-regulation of Ucps by 1,25(OH)2D3, whereas Vdr overexpression strengthened the down-regulation effects. Hairless protein did express in brown adipocyte and was localized in cell nuclei. 1,25(OH)2D3 increased Hairless protein expression in the cell nuclei. Hairless (Hr) silencing notably elevated Ucps expression in activated condition induced by ISO and T3. Moreover, immunoprecipitation results revealed that Vdr could interact with Hairless, which might contribute to decreasing expression of Vdr target gene Ucps. These data suggest that vitamin D suppresses expression of Ucps in brown adipocyte in a Vdr-dependent manner and the corepressor Hairless protein probably plays a role in the down-regulation.

Second messenger signaling mechanisms of the brown adipocyte thermogenic program: an integrative perspective

2017 ◽  
Vol 0 (0) ◽  
Author(s):  
Fubiao Shi ◽  
Sheila Collins
Keyword(s):  
Adipose Tissue ◽  
Natriuretic Peptides ◽  
Second Messenger ◽  
Proton Channel ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Fat Depots ◽  
Signaling Mechanisms ◽  
Brown Adipose ◽  
Non Coding Rnas

Abstractβ-adrenergic receptors (βARs) are well established for conveying the signal from catecholamines to adipocytes. Acting through the second messenger cyclic adenosine monophosphate (cAMP) they stimulate lipolysis and also increase the activity of brown adipocytes and the ‘browning’ of adipocytes within white fat depots (so-called ‘brite’ or ‘beige’ adipocytes). Brown adipose tissue mitochondria are enriched with uncoupling protein 1 (UCP1), which is a regulated proton channel that allows the dissipation of chemical energy in the form of heat. The discovery of functional brown adipocytes in humans and inducible brown-like (‘beige’ or ‘brite’) adipocytes in rodents have suggested that recruitment and activation of these thermogenic adipocytes could be a promising strategy to increase energy expenditure for obesity therapy. More recently, the cardiac natriuretic peptides and their second messenger cyclic guanosine monophosphate (cGMP) have gained attention as a parallel signaling pathway in adipocytes, with some unique features. In this review, we begin with some important historical work that touches upon the regulation of brown adipocyte development and physiology. We then provide a synopsis of some recent advances in the signaling cascades from β-adrenergic agonists and natriuretic peptides to drive thermogenic gene expression in the adipocytes and how these two pathways converge at a number of unexpected points. Finally, moving from the physiologic hormonal signaling, we discuss yet another level of control downstream of these signals: the growing appreciation of the emerging roles of non-coding RNAs as important regulators of brown adipocyte formation and function. In this review, we discuss new developments in our understanding of the signaling mechanisms and factors including new secreted proteins and novel non-coding RNAs that control the function as well as the plasticity of the brown/beige adipose tissue as it responds to the energy needs and environmental conditions of the organism.

scholarly journals White, Brown, Beige/Brite: Different Adipose Cells for Different Functions?

Endocrinology ◽  
2013 ◽  
Vol 154 (9) ◽  
pp. 2992-3000 ◽  
Author(s):  
Marta Giralt ◽  
Francesc Villarroya
Keyword(s):  
Adipose Tissue ◽  
Cell Lineage ◽  
Precursor Cells ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
White Adipocyte ◽  
Brown Adipose ◽  
Adult Humans ◽  
Adipocyte Cell ◽  
Adipose Cells

Brown adipose tissue (BAT) is a major site of nonshivering thermogenesis in mammals. Rodent studies indicated that BAT thermogenic activity may protect against obesity. Recent findings using novel radiodiagnosis procedures revealed unanticipated high activity of BAT in adult humans. Moreover, complex processes of cell differentiation leading to the appearance of active brown adipocytes have been recently identified. The brown adipocytes clustered in defined anatomical BAT depots of rodents arise from mesenchymal precursor cells common to the myogenic cell lineage. They are being called “classical” or “developmentally programmed” brown adipocytes. However, brown adipocytes may appear after thermogenic stimuli at anatomical sites corresponding to white adipose tissue (WAT). This process is called the “browning” of WAT. The brown adipocytes appearing in WAT derive from precursor cells different from those in classical BAT and are closer to the white adipocyte cell lineage. The brown adipocytes appearing in WAT are often called “inducible, beige, or brite.” The appearance of these inducible brown adipocytes in WAT may also involve transdifferentiation processes of white-to-brown adipose cells. There is no evidence that the ultimate thermogenic function of the beige/brite adipocytes differs from that of classical brown adipocytes, although some genetic data in rodents suggest a relevant role of the browning process in protection against obesity. Although the activation of classical BAT and the browning process share common mechanisms of induction (eg, noradrenergic-mediated induction by cold), multiple novel adrenergic-independent endocrine factors that activate BAT and the browning of WAT have been identified recently. In adult humans, BAT is mainly composed of beige/brite adipocytes, although recent data indicate the persistence of classical BAT at some anatomical sites. Understanding the biological processes controlling brown adipocyte activity and differentiation could help the design of BAT-focused strategies to increase energy expenditure and fight against obesity.

Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes

2000 ◽  
Vol 279 (3) ◽  
pp. C670-C681 ◽  
Author(s):  
J. Himms-Hagen ◽  
A. Melnyk ◽  
M. C. Zingaretti ◽  
E. Ceresi ◽  
G. Barbatelli ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Protein ◽  
Protein Composition ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Bat Mitochondria ◽  
Adrenoceptor Agonist ◽  
Brown Adipose ◽  
A Cell

Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT) of rats treated with the β3-adrenoceptor agonist, CL-316243 (CL). Objectives were to determine whether these multilocular adipocytes derived from cells that already existed in the WAT or from proliferation of precursor cells and whether new mitochondria contained in them were typical brown adipocyte mitochondria. Use of 5-bromodeoxyuridine to identify cells that had undergone mitosis during the CL treatment showed that most multilocular cells derived from cells already present in the WAT. Morphological techniques showed that at least a subpopulation of unilocular adipocytes underwent conversion to multilocular mitochondria-rich adipocytes. A small proportion of multilocular adipocytes (∼8%) was positive for UCP1 by immunohistochemistry. Biochemical techniques showed that mitochondrial protein recovered from WAT increased 10-fold and protein isolated from brown adipose tissue (BAT) doubled in CL-treated rats. Stained gels showed a different protein composition of new mitochondria isolated from WAT from that of mitochondria isolated from BAT. Western blotting showed new mitochondria in WAT to contain both UCP1, but at a much lower concentration than in BAT mitochondria, and UCP3, at a higher concentration than that in BAT mitochondria. We hypothesize that multilocular adipocytes present at 7 days of CL treatment have two origins. First, most come from convertible unilocular adipocytes that become multilocular and make many mitochondria that contain UCP3. Second, some come from a cell that gives rise to more typical brown adipocytes that express UCP1.

scholarly journals Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Carolin Muley ◽  
Stefan Kotschi ◽  
Alexander Bartelt
Keyword(s):  
Gene Expression ◽  
Quality Control ◽  
Adipose Tissue ◽  
Cold Exposure ◽  
Protein Quality ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Shivering Thermogenesis

The acclimatization of brown adipose tissue (BAT) to sustained cold exposure requires an adaptive increase in proteasomal protein quality control. Ubiquilins represent a recently identified family of shuttle proteins with versatile functions in protein degradation, such as facilitating substrate targeting and proteasomal degradation. However, whether ubiquilins participate in brown adipocyte function has not been investigated so far. Here, we determine the role of ubiquilins for proteostasis and non-shivering thermogenesis in brown adipocytes. We found that Ubqln1, 2 and 4 are highly expressed in BAT and their expression was induced by cold and proteasomal inhibition. Surprisingly, silencing of ubiquilin gene expression (one or multiple in combinations) did not lead to aggravated ER stress or inflammation. Moreover, ubiquitin level and proteasomal activity under basal conditions were not impacted by loss of ubiquilins. Also, non-shivering thermogenesis measured by norepinephrine-induced respiration remained intact after loss of ubiquilins. In conclusion, ubiquilin proteins are highly abundant in BAT and regulated by cold, but they are dispensable for brown adipocyte proteostasis and thermogenesis.

The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation

2010 ◽  
Vol 298 (6) ◽  
pp. E1244-E1253 ◽  
Author(s):  
G. Barbatelli ◽  
I. Murano ◽  
L. Madsen ◽  
Q. Hao ◽  
M. Jimenez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cold Exposure ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Cold Acclimatization ◽  
Fat Depots ◽  
Gene Coding ◽  
Adrenoceptor Agonist ◽  
Brown Adipose ◽  
Enhanced Expression

The origin of brown adipocytes arising in white adipose tissue (WAT) after cold acclimatization is unclear. Here, we demonstrate that several UCP1-immunoreactive brown adipocytes occurring in WAT after cold acclimatization have a mixed morphology (paucilocular adipocytes). These cells also had a mixed mitochondrioma with classic “brown” and “white” mitochondria, suggesting intermediate steps in the process of direct transformation of white into brown adipocytes (transdifferentiation). Quantitative electron microscopy disclosed that cold exposure (6°C for 10 days) did not induce an increase in WAT preadipocytes. β3-adrenoceptor-knockout mice had a blunted brown adipocyte occurrence upon cold acclimatization. Administration of the β3-adrenoceptor agonist CL316,243 induced the occurrence of brown adipocytes, with the typical morphological features found after cold acclimatization. In contrast, administration of the β1-adrenoceptor agonist xamoterol increased only the number of preadipocytes. These findings indicate that transdifferentiation depends on β3-adrenoceptor activation, whereas preadipocyte recruitment is mediated by β1-adrenoceptor. RT-qPCR experiments disclosed that cold exposure induced enhanced expression of the thermogenic genes and of genes expressed selectively in brown adipose tissue (iBAT) and in both interscapular BAT and WAT. β3-adrenoceptor suppression blunted their expression only in WAT. Furthermore, cold acclimatization induced an increased WAT expression of the gene coding for C/EBPα (an antimitotic protein), whereas Ccna1 expression (related to cell proliferation) was unchanged. Overall, our data strongly suggest that the cold-induced emergence of brown adipocytes in WAT predominantly reflects β3-adrenoceptor-mediated transdifferentiation.

scholarly journals Effects of hypothyroidism and hyperthyroidism on GDP binding to brown-adipocyte mitochondria from rats

1989 ◽  
Vol 263 (2) ◽  
pp. 341-345 ◽  
Author(s):  
J A Woodward ◽  
E D Saggerson
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Dna Content ◽  
Brown Adipocyte ◽  
Thyroid Status ◽  
Mitochondrial Uncoupling ◽  
Brown Adipocytes ◽  
Period 2 ◽  
Brown Adipose

1. Rats were made hypothyroid by giving them a low-iodine diet with propylthiouracil for 4 weeks, or were made hyperthyroid by injection with tri-iodothyronine (T3) over a 3-day period. 2. Brown adipocytes were isolated from the interscapular depots of these animals or from their euthyroid controls, followed by isolation of mitochondria from the cells. 3. Relative to cell DNA content, hypothyroidism decreased the maximum binding (Bmax.) of [3H]GDP to mitochondria by 50%. T3 treatment increased binding by 37%. 4. These findings, which are discussed in relation to previously observed changes in brown adipose tissue after alteration of thyroid status, suggest that mitochondrial uncoupling for thermogenesis is less or more effective in hypothyroidism or hyperthyroidism respectively.

scholarly journals Essential roles of 11β-HSD1 in regulating brown adipocyte function

2012 ◽  
Vol 50 (1) ◽  
pp. 103-113 ◽  
Author(s):  
Juan Liu ◽  
Xiaocen Kong ◽  
Long Wang ◽  
Hanmei Qi ◽  
Wenjuan Di ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
Specific Gene ◽  
Brown Adipocytes ◽  
Expression Of Genes ◽  
Brown Adipose ◽  
Attractive Therapeutic Target ◽  
And Function

Brown adipose tissue (BAT) increases energy expenditure and is an attractive therapeutic target for obesity. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), an amplifier of local glucocorticoid activity, has been shown to modulate white adipose tissue (WAT) metabolism and function. In this study, we investigated the roles of 11β-HSD1 in regulating BAT function. We observed a significant increase in the expression of BAT-specific genes, including UCP1, Cidea, Cox7a1, and Cox8b, in BVT.2733 (a selective inhibitor of 11β-HSD1)-treated and 11β-HSD1-deficient primary brown adipocytes of mice. By contrast, a remarkable decrease in BAT-specific gene expression was detected in brown adipocytes when 11β-HSD1 was overexpressed, which effect was reversed by BVT.2733 treatment. Consistent with the in vitro results, expression of a range of genes related to brown fat function in high-fat diet-fed mice treated with BVT.2733. Our results indicate that 11β-HSD1 acts as a vital regulator that controls the expression of genes related to brown fat function and as such may become a potential target in preventing obesity.

scholarly journals Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice

2020 ◽  
Vol 4 (1) ◽  
pp. e202000924
Author(s):  
Ruth Karlina ◽  
Dominik Lutter ◽  
Viktorian Miok ◽  
David Fischer ◽  
Irem Altun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Expression Profiles ◽  
Stromal Vascular Fraction ◽  
Gene Expression Profiles ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Brown Adipose

Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. Although increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Recently, UCP1 high and low expressing brown adipocytes were identified, but a developmental origin of these subtypes has not been studied. To obtain more insights into brown preadipocyte heterogeneity, we use single-cell RNA sequencing of the BAT stromal vascular fraction of C57/BL6 mice and characterize brown preadipocyte and adipocyte clonal cell lines. Statistical analysis of gene expression profiles from brown preadipocyte and adipocyte clones identify markers distinguishing brown adipocyte subtypes. We confirm the presence of distinct brown adipocyte populations in vivo using the markers EIF5, TCF25, and BIN1. We also demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that BIN1 marks dormant brown adipocytes. The existence of multiple brown adipocyte subtypes suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct functions in thermogenesis and the regulation of whole body energy homeostasis.

PP239-MON: The Effect of Vitamin D on Brown Adipose Tissue in Obesity with Vitamin D Deficiency: Pilot Study

2014 ◽  
Vol 33 ◽  
pp. S218
Author(s):  
S. Rattanachaiwong ◽  
B. Ongphiphadhanakul ◽  
D. Warodomwichit ◽  
C. Sritara
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Pilot Study ◽  
Brown Adipose Tissue ◽  
Vitamin D Deficiency ◽  
Brown Adipose

scholarly journals Immunohistochemical identification of the uncoupling protein in rat brown adipose tissue.

1985 ◽  
Vol 33 (2) ◽  
pp. 150-154 ◽  
Author(s):  
M Cadrin ◽  
M Tolszczuk ◽  
J Guy ◽  
G Pelletier ◽  
K B Freeman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Staining Technique ◽  
Cellular Heterogeneity ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Immunohistochemical Technique ◽  
Brown Adipose ◽  
Pap Method

Brown adipose tissue mitochondria are characterized by the presence of an uncoupling protein that gives them an exceptional capacity for substrate-controlled respiration and thermogenesis. The specific localization of this protein in rat brown adipocytes was demonstrated using an immunohistochemical technique, the peroxidase-antiperoxidase (PAP) method. Light microscopy observations showed that serum antibodies raised against the uncoupling protein selectively reacted with multilocular brown adipocytes. No labeling could be detected in either unilocular adipocytes, capillaries, or muscle fibers (striated and vascular smooth muscle). Staining was more intensive in certain adipocytes than in others, suggesting the presence of cellular heterogeneity. The specificity of the staining technique was demonstrated by showing that treatment of the preparations with antiserum saturated with an excess of uncoupling protein almost entirely inhibited brown adipocyte labeling. The specificity and selectivity of the PAP method allow the clear differentiation of uncoupling protein-containing adipocytes from other cellular types, suggesting that this immunohistochemical technique will represent an extremely useful tool for studying adipocyte function and differentiation.

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