scholarly journals Egr1 loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue

2020 ◽  
Author(s):  
Marianne Bléher ◽  
Berbang Meshko ◽  
Rachel Gergondey ◽  
Yoann Kovacs ◽  
Delphine Duprez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Subcutaneous Fat ◽  
Loss Of Function ◽  
Beige Adipocyte ◽  
Subcutaneous White Adipose Tissue ◽  
Fat Depots ◽  
Beige Adipocytes

AbstractExercise, cold exposure and fasting lead to the differentiation of inducible-brown adipocytes, called beige adipocytes, within white adipose tissue and have beneficial effects on fat burning and metabolism, through heat production. This browning process is associated with an increased expression of the key thermogenic mitochondrial uncoupling protein 1, Ucp1. Egr1 transcription factor has been described as a regulator of white and beige differentiation programs, and Egr1 depletion is associated with a spontaneous increase of subcutaneous white adipose tissue browning, in absence of external stimulation. Here, we demonstrate that Egr1 mutant mice exhibit a restrained Ucp1 expression specifically increased in subcutaneous fat, resulting in a metabolic shift to a more brown-like, oxidative metabolism, which was not observed in other fat depots. In addition, Egr1 is necessary and sufficient to promote white and alter beige adipocyte differentiation of mouse stem cells. These results suggest that modulation of Egr1 expression could represent a promising therapeutic strategy to increase energy expenditure and to restrain obesity-associated metabolic disorders.

scholarly journals Egr1 loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marianne Bléher ◽  
Berbang Meshko ◽  
Isabelle Cacciapuoti ◽  
Rachel Gergondey ◽  
Yoann Kovacs ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Subcutaneous Fat ◽  
Loss Of Function ◽  
Beige Adipocyte ◽  
Subcutaneous White Adipose Tissue ◽  
Fat Depots ◽  
Beige Adipocytes

Abstract In mice, exercise, cold exposure and fasting lead to the differentiation of inducible-brown adipocytes, called beige adipocytes, within white adipose tissue and have beneficial effects on fat burning and metabolism, through heat production. This browning process is associated with an increased expression of the key thermogenic mitochondrial uncoupling protein 1, Ucp1. Egr1 transcription factor has been described as a regulator of white and beige differentiation programs, and Egr1 depletion is associated with a spontaneous increase of subcutaneous white adipose tissue browning, in absence of external stimulation. Here, we demonstrate that Egr1 mutant mice exhibit a restrained Ucp1 expression specifically increased in subcutaneous fat, resulting in a metabolic shift to a more brown-like, oxidative metabolism, which was not observed in other fat depots. In addition, Egr1 is necessary and sufficient to promote white and alter beige adipocyte differentiation of mouse stem cells. These results suggest that modulation of Egr1 expression could represent a promising therapeutic strategy to increase energy expenditure and to restrain obesity-associated metabolic disorders.

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

2020 ◽  
Vol 295 (7) ◽  
pp. 2034-2042 ◽  
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.

scholarly journals Egr1 deficiency induces browning of inguinal subcutaneous white adipose tissue in mice

2017 ◽  
Author(s):  
Cécile Milet ◽  
Marianne Bléher ◽  
Kassandra Allbright ◽  
Mickael Orgeur ◽  
Fanny Coulpier ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
White Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Negative Regulator ◽  
Molecular Signature ◽  
Beige Adipocyte ◽  
Matrix Gene

AbstractBeige adipocyte differentiation within white adipose tissue, referred to as browning, is seen as a possible mechanism for increasing energy expenditure. The molecular regulation underlying the thermogenic browning process has not been entirely elucidated. Here, we identify the zinc finger transcription factor EGR1 as a negative regulator of the beige fat program. Loss of Egr1 in mice promotes browning in the absence of external stimulation and activates Ucp1 that encodes the key thermogenic mitochondrial uncoupling protein-1. Moreover, EGR1 is recruited to the proximal region of the Ucp1 promoter in subcutaneous inguinal white adipose tissue. Transcriptomic analysis of subcutaneous inguinal white adipose tissue in the absence of Egr1 identifies the molecular signature of white adipocyte browning downstream of Egr1 deletion and highlights a concomitant increase of beige differentiation marker and decrease in extracellular matrix gene expression. Conversely, Egr1 overexpression in mesenchymal stem cells decreases beige adipocyte differentiation, while increasing extracellular matrix production. These results uncover the role of Egr1 in blocking energy expenditure via direct Ucp1 transcription regulation and highlight Egr1 as a therapeutic target for counteracting obesity.

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

2015 ◽  
Vol 112 (45) ◽  
pp. 14006-14011 ◽  
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.

scholarly journals Withania somnifera Extract Enhances Energy Expenditure via Improving Mitochondrial Function in Adipose Tissue and Skeletal Muscle

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 431 ◽  
Author(s):  
Da-Hye Lee ◽  
Jiyun Ahn ◽  
Young-Jin Jang ◽  
Hyo-Deok Seo ◽  
Tae-Youl Ha ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Energy Expenditure ◽  
Mitochondrial Function ◽  
Withania Somnifera ◽  
Uncoupling Protein ◽  
Subcutaneous Fat ◽  
Mitochondrial Activity ◽  
Beige Adipocytes

Withania somnifera (WS), commonly known as ashwagandha, possesses diverse biological functions. WS root has mainly been used as an herbal medicine to treat anxiety and was recently reported to have an anti-obesity effect, however, the mechanisms underlying its action remain to be explored. We hypothesized that WS exerts its anti-obesity effect by enhancing energy expenditure through improving the mitochondrial function of brown/beige adipocytes and skeletal muscle. Male C57BL/6J mice were fed a high-fat diet (HFD) containing 0.25% or 0.5% WS 70% ethanol extract (WSE) for 10 weeks. WSE (0.5%) supplementation significantly suppressed the increases in body weight and serum lipids, and lipid accumulation in the liver and adipose tissue induced by HFD. WSE supplementation increased oxygen consumption and enhanced mitochondrial activity in brown fat and skeletal muscle in the HFD-fed mice. In addition, it promoted browning of subcutaneous fat by increasing mitochondrial uncoupling protein 1 (UCP1) expression. Withaferin A (WFA), a major compound of WS, enhanced the differentiation of pre-adipocytes into beige adipocytes and oxygen consumption in C2C12 murine myoblasts. These results suggest that WSE ameliorates diet-induced obesity by enhancing energy expenditure via promoting mitochondrial function in adipose tissue and skeletal muscle, and WFA is a key regulator in this function.

scholarly journals Differential actions of PPAR-α and PPAR-β/δ on beige adipocyte formation: A study in the subcutaneous white adipose tissue of obese male mice

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191365 ◽  
Author(s):  
Tamiris Lima Rachid ◽  
Flavia Maria Silva-Veiga ◽  
Francielle Graus-Nunes ◽  
Isabele Bringhenti ◽  
Carlos Alberto Mandarim-de-Lacerda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Male Mice ◽  
Beige Adipocyte ◽  
Subcutaneous White Adipose Tissue ◽  
Obese Male

Sensory innervation of white adipose tissue

1987 ◽  
Vol 253 (6) ◽  
pp. R942-R944 ◽  
Author(s):  
R. B. Fishman ◽  
J. Dark
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Dorsal Root ◽  
Subcutaneous Fat ◽  
Sensory Information ◽  
Sensory Innervation ◽  
Fluorescent Cell ◽  
Fat Depots ◽  
Total Body Fat ◽  
Total Body

The presumption that sensory information does not arise from white adipose tissue was reevaluated using the neuroanatomical tracer, "true blue." Fluorescent cell bodies were observed in dorsal root ganglia of rats after tracer was implanted into inguinal or dorsal subcutaneous fat depots. Sensory information from adipose tissue may play an important role in the regulation of regional and total body fat mass.

Abundance of beige and brown adipocyte markers in different adipose depots of cattle at 26 months of age

2017 ◽  
Vol 8 (s1) ◽  
pp. s38-s41 ◽  
Author(s):  
K. Komolka ◽  
E. Albrecht ◽  
T. Gotoh ◽  
S. Maak
Keyword(s):  
Messenger Rna ◽  
Uncoupling Protein ◽  
Transmembrane Protein ◽  
Subcutaneous Fat ◽  
Fat Deposition ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Fat Depots ◽  
Beige Adipocytes ◽  
Breed Differences

Activity of brown and beige adipocytes could contribute to breed differences in fat deposition. Therefore, we compared the abundance of markers for adipocyte types in steers from three cattle breeds differing in fat deposition (Japanese Black, Holstein, Charolais). Markers for white (leptin (LEP)), beige (transmembrane protein 26 (TMEM26), uncoupling protein 1 (UCP1)), and brown adipocytes (Zic family member 1 (ZIC1), UCP1) were analysed by quantitative reverse transcription PCR in subcutaneous fat (SCF), intramuscular fat (IMF), intermuscular fat (IRMF), perirenal fat (PF) and visceral fat (VF). LEP messenger RNA (mRNA) was less abundant in VF compared with other depots (P<0.05). TMEM26 was weakly but evenly expressed in all depots in all animals, whereas UCP1 mRNA showed higher individual variation in some depots. ZIC1 was not detectable in VF and PF but abundant in SCF, IMF and even more abundant in IRMF (P<0.05). No significant breed differences were detected. Using antibodies against UCP1, TMEM26 and ZIC1, we demonstrated that fat depots of 26-month-old cattle still comprise different adipocyte types. However, our results did not support the hypothesis that higher energy expenditure associated with higher abundance or activity of beige or brown adipocytes contributed to differences in fat deposition.

scholarly journals ACE2 exerts anti-obesity effect via stimulating brown adipose tissue and induction of browning in white adipose tissue

2019 ◽  
Vol 317 (6) ◽  
pp. E1140-E1149 ◽  
Author(s):  
Yasuhiro Kawabe ◽  
Jun Mori ◽  
Hidechika Morimoto ◽  
Mihoko Yamaguchi ◽  
Satoshi Miyagaki ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Ang Ii ◽  
Angiotensin Converting Enzyme 2 ◽  
Histone Deacetylase 3 ◽  
Subcutaneous White Adipose Tissue ◽  
Protein Levels ◽  
Brown Adipose

The angiotensin II (ANG II)-ANG II type 1 receptor (AT1R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II/AT1R axis via converting ANG II to angiotensin 1–7 (Ang 1–7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1–7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg·kg−1·day−1) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1–7 axis represent a potential therapeutic approach to prevent the development of obesity.

Postnatal development of uncoupling protein, uncoupling protein mRNA, and GLUT4 in adipose tissues of goats

1993 ◽  
Vol 265 (3) ◽  
pp. R676-R682 ◽  
Author(s):  
P. Trayhurn ◽  
M. E. Thomas ◽  
J. S. Keith
Keyword(s):  
Adipose Tissue ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Subcutaneous Fat ◽  
Brown Fat ◽  
Postnatal Life ◽  
Mitochondrial Uncoupling ◽  
Adipose Tissues ◽  
Perirenal Adipose Tissue ◽  
Fat Depots

Adipose tissues have been characterized in newborn goats on the basis of the presence of the 32,000-M(r) mitochondrial uncoupling protein (UCP) diagnostic of brown fat, and early postnatal developmental changes have been determined. Both internal (perirenal, pericardial, and omental) and subcutaneous (hindlimb and neck regions) adipose tissues in newborn goats contained UCP and are therefore brown fat. The insulin-sensitive glucose transporter, GLUT4, was also present in adipose tissues of newborn goats, implying a potential for insulin-stimulated glucose uptake at birth. UCP was still evident in the perirenal fat of goats at 3 wk of age, but the mitochondrial concentration was only 4%, and the amount per cell a mere 0.2%, of that in the newborn. UCP was not detectable, however, in either the omental or subcutaneous adipose tissue at 3 wk of age and had disappeared from the subcutaneous fat before 2 wk. In contrast to UCP, GLUT4 remained throughout the initial 3 wk of postnatal life. The mRNA for UCP was detected in perirenal adipose tissue of newborn goats, indicating that the gene coding for the protein is being expressed at around birth. UCP mRNA was not, however, detectable in the other fat depots; nor was it evident in the perirenal adipose tissue at > or = 2.5 days of age. It is concluded that the adipose tissues of newborn goats (both internal and subcutaneous) represent brown fat and that there is a rapid transition toward white fat over the first weeks of life. This transition occurs at different rates in different depots but is not markedly faster in goats than in other ruminants.(ABSTRACT TRUNCATED AT 250 WORDS)

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