scholarly journals Black Ginseng and Ginsenoside Rb1 Promote Browning by Inducing UCP1 Expression in 3T3-L1 and Primary White Adipocytes

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2747 ◽  
Author(s):  
Seon-Joo Park ◽  
Miey Park ◽  
Anshul Sharma ◽  
Kihyun Kim ◽  
Hae-Jeung Lee
Keyword(s):  
Uncoupling Protein ◽  
Regulatory Element ◽  
Brown Adipocyte ◽  
Specific Marker ◽  
Peroxisome Proliferator ◽  
Ginsenoside Rb1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes ◽  
Pathway Activation ◽  
Black Ginseng

In this study, we investigated the effects of black ginseng (BG) and ginsenoside Rb1, which induced browning effects in 3T3-L1 and primary white adipocytes (PWATs) isolated from C57BL/6 mice. BG and Rb1 suppressed the expressions of CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding transcription factor-1c (SREBP-1c), whereas the expression level of peroxisome proliferator-activated receptor gamma (PPARγ) was increased. Furthermore, BG and Rb1 enhanced the protein expressions of the brown-adipocyte-specific markers PR domain containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and uncoupling protein 1 (UCP1). These results were further supported by immunofluorescence images of mitochondrial biogenesis. In addition, BG and Rb1 induced expressions of brown-adipocyte-specific marker proteins by AMP-activated protein kinase (AMPK) activation. BG and Rb1 exert antiobesity effects by inducing browning in 3T3-L1 cells and PWATs through AMPK-mediated pathway activation. We suggest that BG and Rb1 act as potential functional antiobesity food agents.

scholarly journals Liraglutide suppresses obesity and promotes browning of white fat via miR-27b in vivo and in vitro

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110550
Author(s):  
Xing Wang ◽  
Shuchun Chen ◽  
Dan Lv ◽  
Zelin Li ◽  
Luping Ren ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
White Adipocytes ◽  
White Fat

Objective To investigate the effect of liraglutide on the browning of white fat and the suppression of obesity via regulating microRNA (miR)-27b in vivo and in vitro. Methods Sprague-Dawley rats were fed a high-fat (HF) diet and 3T3-L1 pre-adipocytes were differentiated into mature white adipocytes. Rats and mature adipocytes were then treated with different doses of liraglutide. The mRNA and protein levels of browning-associated proteins, including uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), CCAAT enhancer binding protein β (CEBPβ), cell death-inducing DFFA-like effector A (CIDEA) and peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α), were detected using quantitative real-time polymerase chain reaction and Western blotting. Results Liraglutide decreased body weight and reduced the levels of blood glucose, triglyceride and low-density lipoprotein cholesterol in HF diet-fed rats. Liraglutide increased the levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α in vivo and vitro. The levels of miR-27b were upregulated in HF diet-fed rats, whereas liraglutide reduced the levels of miR-27b. In vitro, overexpression of miR-27b decreased the mRNA and protein levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α. Transfection with the miR-27b mimics attenuated the effect of liraglutide on the browning of white adipocytes. Conclusion Liraglutide induced browning of white adipose through regulation of miR-27b.

scholarly journals The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2433
Author(s):  
Cécilia Colson ◽  
Pierre-Louis Batrow ◽  
Nadine Gautier ◽  
Nathalie Rochet ◽  
Gérard Ailhaud ◽  
...  
Keyword(s):  
Bioactive Compound ◽  
Antagonistic Effect ◽  
Carnosic Acid ◽  
Brown Adipocyte ◽  
Marker Genes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocyte ◽  
White Adipocytes ◽  
And Function

Thermogenic brown and brite adipocytes convert chemical energy from nutrients into heat. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to control fat mass such as in obesity or cachexia. The peroxisome proliferator-activated receptor (PPAR) family plays key roles in the maintenance of adipose tissue and in the regulation of thermogenic activity. Activation of these receptors induce browning of white adipocyte. The purpose of this work was to characterize the role of carnosic acid (CA), a compound used in traditional medicine, in the control of brown/brite adipocyte formation and function. We used human multipotent adipose-derived stem (hMADS) cells differentiated into white or brite adipocytes. The expression of key marker genes was determined using RT-qPCR and western blotting. We show here that CA inhibits the browning of white adipocytes and favors decreased gene expression of thermogenic markers. CA treatment does not affect β-adrenergic response. Importantly, the effects of CA are fully reversible. We used transactivation assays to show that CA has a PPARα/γ antagonistic action. Our data pinpoint CA as a drug able to control PPAR activity through an antagonistic effect. These observations shed some light on the development of natural PPAR antagonists and their potential effects on thermogenic response.

scholarly journals Dopamine directly increases mitochondrial mass and thermogenesis in brown adipocytes

2017 ◽  
Vol 58 (2) ◽  
pp. 57-66 ◽  
Author(s):  
Rose Kohlie ◽  
Nina Perwitz ◽  
Julia Resch ◽  
Sebastian M Schmid ◽  
Hendrik Lehnert ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Cellular Mechanisms ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Mass ◽  
Brown Adipose

Brown adipose tissue (BAT) is key to energy homeostasis. By virtue of its thermogenic potential, it may dissipate excessive energy, regulate body weight and increase insulin sensitivity. Catecholamines are critically involved in the regulation of BAT thermogenesis, yet research has focussed on the effects of noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT thermogenesis, but the cellular mechanisms involved have not been addressed. We employed our extensively characterised murine brown adipocyte cells. D1-like and D2-like receptors were detectable at the protein level. Stimulation with DA caused an increase in cAMP concentrations. Oxygen consumption rates (OCR), mitochondrial membrane potential (Δψm) and uncoupling protein 1 (UCP1) levels increased after 24 h of treatment with either DA or a D1-like specific receptor agonist. A D1-like receptor antagonist abolished the DA-mediated effect on OCR, Δψm and UCP1. DA induced the release of fatty acids, which did not additionally alter DA-mediated increases of OCR. Mitochondrial mass (as determined by (i) CCCP- and oligomycin-mediated effects on OCR and (ii) immunoblot analysis of mitochondrial proteins) also increased within 24 h. This was accompanied by an increase in peroxisome proliferator-activated receptor gamma co-activator 1 alpha protein levels. Also, DA caused an increase in p38 MAPK phosphorylation and pharmacological inhibition of p38 MAPK abolished the DA-mediated effect on Δψm. In summary, our study is the first to reveal direct D1-like receptor and p38 MAPK-mediated increases of thermogenesis and mitochondrial mass in brown adipocytes. These results expand our understanding of catecholaminergic effects on BAT thermogenesis.

scholarly journals Anti-Adipogenic Effects of Delphinidin-3-O-β-Glucoside in 3T3-L1 Preadipocytes and Primary White Adipocytes

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1848 ◽  
Author(s):  
Miey Park ◽  
Anshul Sharma ◽  
Hae-Jeung Lee
Keyword(s):  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Adenosine Monophosphate ◽  
Immunoblot Analysis ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes ◽  
Health Promoting ◽  
Treatment Of Obesity

Delphinidin-3-O-β-glucoside (D3G) is a health-promoting anthocyanin whose anti-obesity activity has not yet been thoroughly investigated. We examined the effects of D3G on adipogenesis and lipogenesis in 3T3-L1 adipocytes and primary white adipocytes using real-time RT-PCR and immunoblot analysis. D3G significantly inhibited the accumulation of lipids in a dose-dependent manner without displaying cytotoxicity. In the 3T3-L1 adipocytes, D3G downregulated the expression of key adipogenic and lipogenic markers, which are known as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor 1 (SREBP1), CCAAT/enhancer-binding protein alpha (C/EBPα), and fatty acid synthase (FAS). Moreover, the relative protein expression of silent mating type information regulation 2 homolog 1 (SIRT1) and carnitine palmitoyltransferase-1 (CPT-1) were increased, alongside reduced lipid levels and the presence of several small lipid droplets. Furthermore, D3G increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which suggests that D3G may play a role in AMPK and ACC activation in adipocytes. Our data indicate that D3G attenuates adipogenesis and promotes lipid metabolism by activating AMPK-mediated signaling, and, hence, could have a therapeutic role in the management and treatment of obesity.

scholarly journals Fruit of Gardenia jasminoides Induces Mitochondrial Activation and Non-Shivering Thermogenesis through Regulation of PPARγ

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1418
Author(s):  
Woo Yong Park ◽  
Gahee Song ◽  
Ja Yeon Park ◽  
Kwan-Il Kim ◽  
Kwang Seok Ahn ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Exposure Model ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Gardenia Jasminoides ◽  
White Adipocytes ◽  
Beige Adipocytes ◽  
Underlying Mechanisms ◽  
Induced Changes

The extract of the Gardenia jasminoides fruit (GJFE) can been consumed as an herbal tea or used as a yellow dye. Recently, studies report that GFJE exerts inhibitory effects on lipid accumulation and adipogenesis in white adipocytes. We evaluated the thermogenic actions of GJFE by focusing on mitochondrial activation and studying the underlying mechanisms. To investigate the role of GJFE on thermogenesis in mice, we used an acute cold exposure model. After 2 weeks of feeding, the cold tolerance of GJFE-fed mice was notably increased compared to PBS-fed mice. This was due to an increase in thermogenic proteins in the inguinal white adipose tissue of the cold-exposed mice. Moreover, GJFE significantly increased thermogenic factors such as peroxisome proliferator-activated receptor gamma (PPARγ), uncoupling protein 1 (UCP1), and PPARγ coactivator 1 alpha (PGC1α) in vitro as well. Factors related to mitochondrial abundance and functions were also induced by GJFE in white and beige adipocytes. However, the treatment of PPARγ inhibitor abolished the GJFE-induced changes, indicating that activation of PPARγ is critical for the thermogenic effect of GJFE. In conclusion, GJFE induces thermogenic action by activating mitochondrial function via PPARγ activation. Through these findings, we suggest GJFE as a potential anti-obesity agent with a novel mechanism involving thermogenic action in white adipocytes.

scholarly journals Restoration of sterol-regulatory-element-binding protein-1c gene expression in HepG2 cells by peroxisome-proliferator-activated receptor-γ co-activator-1α

2004 ◽  
Vol 381 (2) ◽  
pp. 357-363 ◽  
Author(s):  
Hannes OBERKOFLER ◽  
Elisabeth SCHRAML ◽  
Franz KREMPLER ◽  
Wolfgang PATSCH
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Hepg2 Cells ◽  
Binding Protein ◽  
Regulatory Element ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

The expression of SREBP-1 (sterol-regulatory-element-binding protein-1) isoforms differs between tissues and cultured cell lines in that SREBP-1a is the major isoform in established cell lines, whereas SREBP-1c predominates in liver and most other human tissues. SREBP-1c is transcriptionally less active than SREBP-1a, but is a main mediator of hepatic insulin action and is selectively up-regulated by LXR (liver X receptor) agonists. LXR-mediated transactivation is co-activated by PGC-1α (peroxisome-proliferator-activated receptor-γ co-activator-1α), which displays deficient expression in skeletal-muscle-derived cell lines. In the present paper, we show that PGC-1α expression is also deficient in HepG2 cells and in a human brown adipocyte cell line (PAZ6). In transient transfection studies, PGC-1α selectively amplified the LXR-mediated transcription from the human SREBP-1c promoter in HepG2 and PAZ6 cells via two LXR-response elements with extensive similarity to the respective murine sequence. Mutational analysis showed that the human LXR-response element-1 (hLXRE-1) was essential for co-activation of LXR-mediated SREBP-1c gene transcription by PGC-1α. Ectopic overexpression of PGC-1α in HepG2 cells enhanced basal SREBP-1c and, to a lesser extent, -1a mRNA expression, but only SREBP-1c expression was augmented further in an LXR/RXR (retinoic X receptor)-dependent fashion, thereby inducing mRNA abundance levels of SREBP-1c target genes, fatty acid synthase and acetyl-CoA carboxylase. These results indicate that PGC-1α contributes to the regulation of SREBP-1 gene expression, and can restore the SREBP-1 isoform expression pattern of HepG2 cells to that of human liver.

scholarly journals Effects of physical activity on the link between PGC-1a and FNDC5 in muscle, circulating Ιrisin and UCP1 of white adipocytes in humans: A systematic review

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 286 ◽  
Author(s):  
Petros C. Dinas ◽  
Ian M. Lahart ◽  
James A. Timmons ◽  
Per-Arne Svensson ◽  
Yiannis Koutedakis ◽  
...  
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Uncoupling Protein ◽  
Positive Association ◽  
Peroxisome Proliferator ◽  
Activity Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Response To Exercise

Background: Exercise may activate a brown adipose-like phenotype in white adipose tissue. The aim of this systematic review was to identify the effects of physical activity on the link between peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and fibronectin type III domain-containing protein 5 (FNDC5) in muscle, circulating Irisin and uncoupling protein one (UCP1) of white adipocytes in humans. Methods: Two databases (PubMed 1966 to 08/2016 and EMBASE 1974 to 08/2016) were searched using an appropriate algorithm. We included articles that examined physical activity and/or exercise in humans that met the following criteria: a) PGC-1a in conjunction with FNDC5 measurements, and b) FNDC5 and/or circulating Irisin and/or UCP1 levels in white adipocytes. Results: We included 51 studies (12 randomised controlled trials) with 2474 participants. Out of the 51 studies, 16 examined PGC-1a and FNDC5 in response to exercise, and only four found increases in both PGC-1a and FNDC5 mRNA and one showed increased FNDC5 mRNA. In total, 22 out of 45 studies that examined circulating Irisin in response to exercise showed increased concentrations when ELISA techniques were used; two studies also revealed increased Irisin levels measured via mass spectrometry. Three studies showed a positive association of circulating Irisin with physical activity levels. One study found no exercise effects on UCP1 mRNA in white adipocytes. Conclusions: The effects of physical activity on the link between PGC-1a, FNDC5 mRNA in muscle and UCP1 in white human adipocytes has attracted little scientific attention. Current methods for Irisin identification lack precision and, therefore, the existing evidence does not allow for conclusions to be made regarding Irisin responses to physical activity. We found a contrast between standardised review methods and accuracy of the measurements used. This should be considered in future systematic reviews.

scholarly journals Receptor Interacting Protein 140 Regulates Expression of Uncoupling Protein 1 in Adipocytes through Specific Peroxisome Proliferator Activated Receptor Isoforms and Estrogen-Related Receptor α

2007 ◽  
Vol 21 (7) ◽  
pp. 1581-1592 ◽  
Author(s):  
Darja Debevec ◽  
Mark Christian ◽  
Daniel Morganstein ◽  
Asha Seth ◽  
Birger Herzog ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
White Adipocytes ◽  
Receptor Isoforms ◽  
Ucp1 Expression ◽  
Peroxisome Proliferator Activated Receptors ◽  
Estrogen Related Receptor

Abstract Expression of uncoupling protein 1 (Ucp1) mRNA is elevated in differentiated adipocytes derived from brown or white adipose tissue devoid of the nuclear receptor corepressor receptor interacting protein 140 (RIP140). Increased expression is mediated in part by the recruitment of peroxisome proliferator activated receptors α and γ, together with estrogen-related receptor α, which functions through a novel binding site on the Ucp1 enhancer. This demonstrates that regulation of Ucp1 expression in the absence of RIP140 involves derepression of at least three different nuclear receptors. The ability to increase expression of Ucp1 by β-adrenergic signaling is independent of RIP140, as shown by the action of the β3-adrenergic agonist CL 316,243 to stimulate expression in both brown and white adipocytes in the presence and absence of the corepressor. Therefore, the expression of this metabolic uncoupling protein in adipose cells is regulated by inhibition as well as activation of distinct signaling pathways.

scholarly journals Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Kinyui Alice Lo ◽  
Lei Sun
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Uncoupling Protein ◽  
Transcriptional Regulators ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Pr Domain

Adipose tissue has a central role in the regulation of energy balance and homoeostasis. There are two main types of adipose tissue: WAT (white adipose tissue) and BAT (brown adipose tissue). WAT from certain depots, in response to appropriate stimuli, can undergo a process known as browning where it takes on characteristics of BAT, notably the induction of UCP1 (uncoupling protein 1) expression and the presence of multilocular lipid droplets and multiple mitochondria. How browning is regulated is an intense topic of investigation as it has the potential to tilt the energy balance from storage to expenditure, a strategy that holds promise to combat the growing epidemic of obesity and metabolic syndrome. This review focuses on the transcriptional regulators as well as various proteins and secreted mediators that have been shown to play a role in browning. Emphasis is on describing how many of these factors exert their effects by regulating the three main transcriptional regulators of classical BAT development, namely PRDM16 (PR domain containing 16), PPARγ (peroxisome proliferator-activated receptor γ) and PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α), which have been shown to be the key nodes in the regulation of inducible brown fat.

scholarly journals Effects of physical activity on the link between PGC-1a and FNDC5 in muscle, circulating Ιrisin and UCP1 of white adipocytes in humans: A systematic review

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 286 ◽  
Author(s):  
Petros C. Dinas ◽  
Ian M. Lahart ◽  
James A. Timmons ◽  
Per-Arne Svensson ◽  
Yiannis Koutedakis ◽  
...  
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Uncoupling Protein ◽  
Positive Association ◽  
Peroxisome Proliferator ◽  
Activity Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Response To Exercise

Background: Exercise may activate a brown adipose-like phenotype in white adipose tissue. The aim of this systematic review was to identify the effects of physical activity on the link between peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and fibronectin type III domain-containing protein 5 (FNDC5) in muscle, circulating Irisin and uncoupling protein one (UCP1) of white adipocytes in humans. Methods: Two databases (PubMed 1966 to 08/2016 and EMBASE 1974 to 08/2016) were searched using an appropriate algorithm. We included articles that examined physical activity and/or exercise in humans that met the following criteria: a) PGC-1a in conjunction with FNDC5 measurements, and b) FNDC5 and/or circulating Irisin and/or UCP1 levels in white adipocytes. Results: We included 51 studies (12 randomised controlled trials) with 2474 participants. Out of the 51 studies, 16 examined PGC-1a and FNDC5 in response to exercise, and only four found increases in both PGC-1a and FNDC5 mRNA and one showed increased FNDC5 mRNA. In total, 22 out of 45 studies that examined circulating Irisin in response to exercise showed increased concentrations when ELISA techniques were used; two studies also revealed increased Irisin levels measured via mass spectrometry. Three studies showed a positive association of circulating Irisin with physical activity levels. One study found no exercise effects on UCP1 mRNA in white adipocytes. Conclusions: The effects of physical activity on the link between PGC-1a, FNDC5 mRNA in muscle and UCP1 in white human adipocytes has attracted little scientific attention. Current methods for Irisin identification lack precision and, therefore, the existing evidence does not allow for conclusions to be made regarding Irisin responses to physical activity. We found a contrast between standardised review methods and accuracy of the measurements used. This should be considered in future systematic reviews.

Sign in / Sign up

Export Citation Format

Share Document