scholarly journals Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chul-Hong Park ◽  
Jiyoung Moon ◽  
Minsung Park ◽  
Helia Cheng ◽  
Jisu Lee ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adrenergic Receptor ◽  
Phosphorylation Site ◽  
Specific Gene ◽  
Serine Threonine Kinase ◽  
Additional Layer ◽  
Beige Adipocytes ◽  
Pka Pathway ◽  
Beige Adipose Tissue

Brown and beige adipocytes are specialized to dissipate energy as heat. Sgk2, encoding a serine/threonine kinase, has been identified as a brown and beige adipocyte-specific gene in rodents and humans; however, its function in brown/beige adipocytes remains unraveled. Here, we examined the regulation and role of Sgk2 in brown/beige adipose tissue thermogenesis. We found that transcriptional coactivators PGC-1α and NT-PGC-1α activated by the β3 adrenergic receptor-cAMP-PKA pathway are recruited to the Sgk2 promoter, triggering Sgk2 transcription in response to cold. SGK2 elevation was closely associated with increased serine/threonine phosphorylation of proteins carrying the consensus RxRxxS/T phosphorylation site. However, despite cold-dependent activation of SGK2, mice lacking Sgk2 exhibited normal cold tolerance at 4°C. In addition, Sgk2+/+ and Sgk2−/− mice induced comparable increases in energy expenditure during pharmacological activation of brown and beige adipose tissue with a β3AR agonist. In vitro loss- and gain-of-function studies further demonstrated that Sgk2 ablation or activation does not alter thermogenic gene expression and mitochondrial respiration in brown adipocytes. Collectively, our results reveal a new signaling component SGK2, although dispensable for cold-induced thermogenesis that adds an additional layer of complexity to the β3AR signaling network in brown/beige adipose tissue.

scholarly journals In Vitro and In Vivo Impairment of α2-Adrenergic Receptor-Dependent Antilipolysis by Fatty Acids in Human Adipose Tissue

2001 ◽  
Vol 33 (12) ◽  
pp. 701-707 ◽  
Author(s):  
S. Gesta ◽  
J. Hejnova ◽  
M. Berlan ◽  
D. Daviaud ◽  
F. Crampes ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Adrenergic Receptor ◽  
Human Adipose Tissue

Fibrinogen Concentration Influence on VEGF-Induced Differentiation of Adipose Tissue-Derived Stem Cells into Endothelial Cells

2007 ◽  
Vol 342-343 ◽  
pp. 17-20
Author(s):  
Hyeong In Kim ◽  
Ji Yeon Seo ◽  
Seung Jo Jeung ◽  
Sae Gwang Park ◽  
Young Il Yang
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Adipose Tissue ◽  
Network Formation ◽  
Capillary Tube ◽  
Specific Gene ◽  
Fibrinogen Concentration ◽  
And Migration ◽  
Von Willebrand

Fibrin is a natural substrate for growth, adhesion, and migration of mature endothelial cells (ECs) and a candidate coating material in approaches to graft endothelialization. Adipose tissue represents an abundant, practical source of donor tissue for stem cells which may be a useful source for engineering of vascular grafts. However, the optimal substrates that promote differentiation of adipose tissue-derived stem cells (ASCs) into ECs remain to be elucidated. In the present study, we investigated whether fibrin can be used as a substratum to support in vitro ECs differentiation of ASCs and whether fibrinogen concentration can be affect on ECs differentiation of ASCs. For determination of phenotypic characteristics of ASCs used in this experiment, we performed flow cytometry analysis. ASCs were plated on fibrin composed of varying concentrations of fibrinogen and induced into ECs differentiation in presence of VEGF. Before inducing into ECs, ASCs did not express any markers of hematopoietic cells (CD34, CD45), ECs (CD31, CD34), and endothelial progenitor cells (CD34, CD133, Flk-1). The degree of ECs differentiation was determined by capillary network formation, ECs-specific gene expression, and F-actin assembly. During the first 12 h after seeding, cells spread randomly, moved and formed small interconnected clusters. These clusters decreased in size and formed a capillary tube at 48 h. During the further incubation in presence of VEGF for 7 days, ASCs expressed mRNA and protein of von Willebrand factor (vWF). The degree of ECs differentiation of ASCs was consistently decreased as fibrinogen concentration increase. Fibrin may be used as biomatrix to promote differentiation of ASCs into ECs for tissue engineering.

scholarly journals Beige Adipose Tissue Identification and Marker Specificity—Overview

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna-Claire Pilkington ◽  
Henry A. Paz ◽  
Umesh D. Wankhade
Keyword(s):  
Adipose Tissue ◽  
Molecular Features ◽  
Tissue Identification ◽  
Excessive Weight ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Different Types ◽  
Similar Appearance ◽  
Beige Adipose Tissue ◽  
Ubiquitous Presence

Adipose tissue (AT) is classified based on its location, physiological and functional characteristics. Although there is a clear demarcation of anatomical and molecular features specific to white (WAT) and brown adipose tissue (BAT), the factors that uniquely differentiate beige AT (BeAT) remain to be fully elaborated. The ubiquitous presence of different types of AT and the inability to differentiate brown and beige adipocytes because of similar appearance present a challenge when classifying them one way or another. Here we will provide an overview of the latest advances in BeAT, BAT, and WAT identification based on transcript markers described in the literature. The review paper will highlight some of the difficulties these markers pose and will offer new perspectives on possible transcript-specific identification of BeAT. We hope that this will advance the understanding of the biology of different ATs. In addition, concrete strategies to distinguish different types of AT may be relevant to track the efficacy and mechanisms around interventions aimed to improve metabolic health and thwart excessive weight gain.

rZIP, a RING-leucine zipper protein that regulates cell fate determination during Dictyostelium development

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1203-1213 ◽  
Author(s):  
P. Balint-Kurti ◽  
G. Ginsburg ◽  
O. Rivero-Lezcano ◽  
A.R. Kimmel
Keyword(s):  
Cell Fate ◽  
Leucine Zipper ◽  
Phosphorylation Site ◽  
Adaptor Protein ◽  
Specific Gene ◽  
Cell Fate Decisions ◽  
Cellular Aggregation ◽  
Constitutive Overexpression ◽  
Zinc Binding Domain

rZIP is an approx. 32 kDa, multi-domain protein of Dictyostelium discoideum whose structural motifs include a RING (zinc-binding) domain, a leucine zipper, a glutamine repeat, an SH3-binding region and a consensus phosphorylation site for MAP kinase. In vitro, rZIP forms homodimers and interacts specifically with the SH3 domain(s) of the Nck adaptor protein. rZIP is expressed maximally during cell differentiation at approximately equivalent levels in all cells. Disruption of the rZIP gene rzpA results in altered cellular aggregation, impaired slug migration, and aberrant patterning of prespore and prestalk cells, the major progenitor classes. In rzpA- strains, prespore-specific genes are overexpressed and prestalk expression zones are reduced. Conversely, constitutive overexpression of rzpA markedly decreases prespore-specific gene expression and significantly increases the expression of prestalk-specific genes. Further, induced transdifferentiation of prespore cells into prestalk cells is inhibited in rzpA-slugs. In light of these patterning defects, we suggest that the RING/zipper protein rZIP plays an important role in early cell fate decisions in Dictyostelium, acting as a positive regulator of prestalk differentiation and an inhibitor of prespore differentiation.

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 Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lisa Suwandhi ◽  
Irem Altun ◽  
Ruth Karlina ◽  
Viktorian Miok ◽  
Tobias Wiedemann ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Tissue Expansion ◽  
White Adipocyte ◽  
The Metabolic Syndrome ◽  
Beige Adipocytes ◽  
Subcutaneous Adipose ◽  
Old Mice

AbstractAdipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.

scholarly journals Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ningning Bai ◽  
Jingyuan Ma ◽  
Miriayi Alimujiang ◽  
Jun Xu ◽  
Fan Hu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxidative Capacity ◽  
Mrna Levels ◽  
Cluster Assembly ◽  
Respiratory Chain Complexes ◽  
Beige Adipocyte ◽  
Mitochondrial Homeostasis ◽  
Beige Adipocytes ◽  
Beige Fat

Mitochondrial iron-sulfur (Fe-S) cluster is an important cofactor for the maturation of Fe-S proteins, which are ubiquitously involved in energy metabolism; however, factors facilitating this process in beige fat have not been established. Here, we identified BolA family member 3 (Bola3), as one of 17 mitochondrial Fe-S cluster assembly genes, was the most significant induced gene in the browning program of white adipose tissue. Using lentiviral-delivered shRNA in vitro, we determined that Bola3 deficiency inhibited thermogenesis activity without affecting lipogenesis in differentiated beige adipocytes. The inhibition effect of Bola3 knockdown might be through impairing mitochondrial homeostasis and lipolysis. This was evidenced by the decreased expression of mitochondria related genes and respiratory chain complexes, attenuated mitochondrial formation, reduced mitochondrial maximal respiration and inhibited isoproterenol-stimulated lipolysis. Furthermore, BOLA3 mRNA levels were higher in human deep neck brown fat than in the paired subcutaneous white fat, and were positively correlated with thermogenesis related genes (UCP1, CIDEA, PRDM16, PPARG, COX7A1, and LIPE) expression in human omental adipose depots. This study demonstrates that Bola3 is associated with adipose tissue oxidative capacity both in mice and human, and it plays an indispensable role in beige adipocyte thermogenesis via maintaining mitochondrial homeostasis and adrenergic signaling-induced lipolysis.

ALPHA-ADRENERGIC RECEPTOR ACTIVITY, CYCLIC AMP AND LIPOLYSIS IN ADIPOSE TISSUE OF HYPOTHYROID MAN AND RAT

1976 ◽  
Vol 68 (3) ◽  
pp. 419-430 ◽  
Author(s):  
J. P. D. RECKLESS ◽  
C. H. GILBERT ◽  
D. J. GALTON
Keyword(s):  
Adipose Tissue ◽  
Cyclic Amp ◽  
Adrenergic Receptor ◽  
Phosphodiesterase Inhibitor ◽  
Human Adipose Tissue ◽  
Receptor Activity ◽  
Thyroid Function Tests ◽  
Adrenergic Activity ◽  
Rat Adipose Tissue

SUMMARY Lipolysis and intracellular levels of cyclic AMP of adipose tissue from man and rat in both hypothyroid and euthyroid states were studied in response to stimulation by catecholamines in vitro. Hypothyroid patients were studied before and after treatment, and were also compared with euthyroid obese controls. The experimental group of rats was rendered hypothyroid by the addition of 2·9 mm-propylthiouracil to their drinking water, and their status confirmed by plasma thyroid function tests. Evidence for α-adrenergic receptor activity was found in rat adipose tissue, but was less marked than the pronounced α-adrenergic activity in human adipose tissue. Glycerol release from adipose tissue in response to noradrenaline stimulation was less marked in hypothyroidism in both species, and was related to an increased α-adrenergic activity. No evidence was found for increased α-adrenergic effects on cyclic AMP level in hypothyroid subjects, and little evidence was found in adipose tissue from hypothyroid rats. This discrepancy may be due to the presence of the phosphodiesterase inhibitor, theophylline, in the incubation system. The possible modulatory role of thyroid hormones on receptor and phosphodiesterase activity, and on lipolysis, is discussed.

scholarly journals Metabolic characteristics and therapeutic potential of brown and ?beige? adipose tissues

2014 ◽  
Vol 17 (4) ◽  
pp. 5-15 ◽  
Author(s):  
Ekaterina Olegovna Koksharova ◽  
Alexander Yur'evich Mayorov ◽  
Marina Vladimirovna Shestakova ◽  
Ivan Ivanovich Dedov
Keyword(s):  
Adipose Tissue ◽  
Therapeutic Potential ◽  
Significant Risk ◽  
International Diabetes Federation ◽  
Fibroblast Growth Factor 21 ◽  
Resonance Spectroscopy ◽  
Positive Effects ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Adipose Tissue

According to the International Diabetes Federation, 10.9 million people have diabetes mellitus (DM) in Russia; however, only up to 4 million are registered. In addition, 11.9 million people have impaired glucose tolerance and impaired fasting glucose levels [1]. One of the significant risk factors for type 2 DM (T2DM) is obesity, which increases insulin resistance (IR). IR is the major pathogenetic link to T2DM. According to current concepts, there are three types of adipose tissue: white adipose tissue (WAT), brown adipose tissue (BAT) and ?beige?, of which the last two types have a thermogenic function. Some research results have revealed the main stages in the development of adipocytes; however, there is no general consensus regarding the development of ?beige? adipocytes. Furthermore, the biology of BAT and ?beige? adipose tissue is currently being intensively investigated, and some key transcription factors, signalling pathways and hormones that promote the development and activation of these tissues have been identified. The most discussed hormones are irisin and fibroblast growth factor 21, which have established positive effects on BAT and ?beige? adipose tissue with regard to carbohydrate, lipid and energy metabolism. The primary imaging techniques used to investigate BAT are PET-CT with 18F-fluorodeoxyglucose and magnetic resonance spectroscopy. With respect to the current obesity epidemic and associated diseases, including T2DM, there is a growing interest in investigating adipogenesis and the possibility of altering this process. BAT and ?beige? adipose tissue may be targets for developing drugs directed against obesity and T2DM.

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