scholarly journals GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 162
Author(s):  
JooYeon Jhun ◽  
Jin Seok Woo ◽  
Seung Hoon Lee ◽  
Jeong-Hee Jeong ◽  
KyungAh Jung ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Treg Cells ◽  
Mitochondrial Superoxide ◽  
Glucose And Lipid Metabolism ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Increased Risk ◽  
White Fat ◽  
Excessive Accumulation

Obesity, a condition characterized by excessive accumulation of body fat, is a metabolic disorder related to an increased risk of chronic inflammation. Obesity is mediated by signal transducer and activator of transcription (STAT) 3, which is regulated by genes associated with retinoid-interferon-induced mortality (GRIM) 19, a protein ubiquitously expressed in various human tissues. In this study, we investigated the role of GRIM19 in diet-induced obese C57BL/6 mice via intravenous or intramuscular administration of a plasmid encoding GRIM19. Splenocytes from wild-type and GRIM19-overexpressing mice were compared using enzyme-linked immunoassay, real-time polymerase chain reaction, Western blotting, flow cytometry, and histological analyses. GRIM19 attenuated the progression of obesity by regulating STAT3 activity and enhancing brown adipose tissue (BAT) differentiation. GRIM19 regulated the differentiation of mouse-derived 3T3-L1 preadipocytes into adipocytes, while modulating gene expression in white adipose tissue (WAT) and BAT. GRIM19 overexpression reduced diet-induced obesity and enhanced glucose and lipid metabolism in the liver. Moreover, GRIM19 overexpression reduced WAT differentiation and induced BAT differentiation in obese mice. GRIM19-transgenic mice exhibited reduced mitochondrial superoxide levels and a reciprocal balance between Th17 and Treg cells. These results suggest that GRIM19 attenuates the progression of obesity by controlling adipocyte differentiation.

scholarly journals Phosphocholine accumulation and PHOSPHO1 depletion promote adipose tissue thermogenesis

2020 ◽  
Vol 117 (26) ◽  
pp. 15055-15065 ◽  
Author(s):  
Mengxi Jiang ◽  
Tony E. Chavarria ◽  
Bingbing Yuan ◽  
Harvey F. Lodish ◽  
Nai-Jia Huang
Keyword(s):  
Adipose Tissue ◽  
Negative Regulator ◽  
Brown Adipocytes ◽  
Diet Induced Obesity ◽  
The Metabolic Syndrome ◽  
Brown Adipose ◽  
Cold Tolerant ◽  
Functional Relevance ◽  
Hydrolysis Of

Phosphocholine phosphatase-1 (PHOSPHO1) is a phosphocholine phosphatase that catalyzes the hydrolysis of phosphocholine (PC) to choline. Here we demonstrate that the PHOSPHO1 transcript is highly enriched in mature brown adipose tissue (BAT) and is further induced by cold and isoproterenol treatments of BAT and primary brown adipocytes. In defining the functional relevance of PHOPSPHO1 in BAT thermogenesis and energy metabolism, we show that PHOSPHO1 knockout mice are cold-tolerant, with higher expression of thermogenic genes in BAT, and are protected from high-fat diet-induced obesity and development of insulin resistance. Treatment of mice with the PHOSPHO1 substrate phosphocholine is sufficient to induce cold tolerance, thermogenic gene expression, and allied metabolic benefits. Our results reveal a role of PHOSPHO1 as a negative regulator of BAT thermogenesis, and inhibition of PHOSPHO1 or enhancement of phosphocholine represent innovative approaches to manage the metabolic syndrome.

scholarly journals White, beige and brown adipose tissue: structure, function, specific features and possibility formation and divergence in pigs

2021 ◽  
pp. 10-18
Author(s):  
Irina Chernukha ◽  
Liliya Fedulova ◽  
Elena Kotenkova
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
The Body ◽  
Intermediate Form ◽  
Swine Industry ◽  
Brown Adipose ◽  
Beige Fat ◽  
White Fat ◽  
The Impact

Introduction. Traditionally, mammalian adipose tissue is divided into white (white adipose tissue – WAT) and brown (brown adipose tissue – BAT). While the functions of WAT are well known as the triglyceride depot, the role of BAT in mammalian physiology has been under close investigation. The first description of the role of BAT in maintaining thermogenesis dates back to 1961. This article offers a review of structural and functional specificity of white, beige and brown adipose tissue. Results and discussion. The differences and descriptions of adipocytes and their impact on the maintenance of the main functions of the mammalian body are described in this manuscript. In particular, thermogenesis, stress response, obesity, type II diabetes. In addition to WAT and BAT, an intermediate form was also detected in the body – beige fat (BeAT or Brite). The opposite opinions regarding the presence of three types of adipose tissue in the human and animal bodies are presented. Studies on the identification of uncoupling proteins 1 and 3 and their role in the transformation of white fat into beige/brown are considered. Basically, the data on the factors of endogenous and exogenous nature on their formation are given on the example of the human body. Conclusion. With an abundance of publications on the keywords: “white, brown fat”, these studies, in the overwhelming majority, are devoted to the role of these fats in the formation of human thermogenesis, the assessment of the impact on obesity. Pigs have also been suggested to lack functional BAT, which is a major cause of neonatal death in the swine industry, therefore the focus on investigating role of different types of adipose tissue in pigs seems very promising in order to understand whether there is a compensating mechanism of thermogenesis.

scholarly journals Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation

2014 ◽  
Vol 307 (9) ◽  
pp. E793-E799 ◽  
Author(s):  
G. Andres Contreras ◽  
Yun-Hee Lee ◽  
Emilio P. Mottillo ◽  
James G. Granneman
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Sympathetic Innervation ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Main Site ◽  
Adipose Tissue Depots ◽  
Brown Adipose ◽  
White Fat

Brown adipocytes (BA) generate heat in response to sympathetic activation and are the main site of nonshivering thermogenesis in mammals. Although most BA are located in classic brown adipose tissue depots, BA are also abundant in the inguinal white adipose tissue (iWAT) before weaning. The number of BA is correlated with the density of sympathetic innervation in iWAT; however, the role of continuous sympathetic tone in the establishment and maintenance of BA in WAT has not been investigated. BA marker expression in iWAT was abundant in weaning mice but was greatly reduced by 8 wk of age. Nonetheless, BA phenotype could be rapidly reinstated by acute β3-adrenergic stimulation with CL-316,243 (CL). Genetic tagging of adipocytes with adiponectin-CreERT2 demonstrated that CL reinstates uncoupling protein 1 (UCP1) expression in adipocytes that were present before weaning. Chronic surgical denervation dramatically reduced the ability of CL to induce the expression of UCP1 and other BA markers in the tissue as a whole, and this loss of responsiveness was prevented by concurrent treatment with CL. These results indicate that ongoing sympathetic activity is critical to preserve the ability of iWAT fat cells to express a BA phenotype upon adrenergic stimulation.

scholarly journals Modulation of Type I Iodothyronine 5’-Deiodinase Activity in white Adipose Tissue by Nutrition: Possible Involvement of Leptin

2010 ◽  
pp. 561-569
Author(s):  
Z Macek Jílková ◽  
S Pavelka ◽  
P Flachs ◽  
M Hensler ◽  
V Kůs ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Caloric Restriction ◽  
White Adipose Tissue ◽  
Type I ◽  
Metabolizing Enzymes ◽  
Tissue Metabolism ◽  
Brown Adipose ◽  
Plasma Leptin ◽  
White Fat

Adipose tissue is an important target for thyroid hormones (TH). However, the metabolism of TH in white adipose tissue is poorly characterized. Our objective was to describe possible changes in activities of TH-metabolizing enzymes in white adipose tissue, and the role of TH metabolism in the tissue during obesogenic treatment, caloric restriction and in response to leptin in mice. Activity of type I iodothyronine 5’-deiodinase (D1) in white fat was stimulated by a high-fat diet, which also increased plasma leptin levels, while brown adipose tissue D1 activity did not change. Caloric restriction decreased the activity of D1 in white fat (but not in the liver), reduced leptin levels, and increased the expression of stearoyl CoA desaturase 1 (SCD-1), a marker and mediator of the effect of leptin on tissue metabolism. Leptin injections increased D1 activity and down-regulated SCD-1 in white fat. Our results demonstrate changes in D1 activity in white adipose tissue under the conditions of changing adiposity, and a stimulatory effect of leptin on D1 activity in the tissue. These results suggest a functional role for D1 in white adipose tissue, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue.

Adipokines: inflammation and the pleiotropic role of white adipose tissue

2022 ◽  
Vol 127 (2) ◽  
pp. 161-164
Author(s):  
Paul Trayhurn
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Physiological Role ◽  
Storage Organ ◽  
Multiple Functions ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Simple Lipid ◽  
White Fat

I had been working on the endocrine and signalling role of white adipose tissue (WAT) since 1994 following the identification of the ob (Lep) gene(1), this after some 15 years investigating the physiological role of brown adipose tissue. The ob gene, a mutation in which it is responsible for the profound obesity of ob/ob (Lepob/Lepob) mice, is expressed primarily in white adipocytes and encodes the pleiotropic hormone leptin. The discovery of this adipocyte hormone had wide-ranging implications, including that white fat has multiple functions that far transcend the traditional picture of a simple lipid storage organ.

scholarly journals The autocrine role of FGF21 in cultured adipocytes

2020 ◽  
Vol 477 (13) ◽  
pp. 2477-2487
Author(s):  
Sarah Justesen ◽  
Kirsten V. Haugegaard ◽  
Jacob B. Hansen ◽  
Harald S. Hansen ◽  
Birgitte Andersen
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Cell Lines ◽  
Fibroblast Growth Factor 21 ◽  
Adrenergic Stimulation ◽  
Fgf Receptor ◽  
Glucose And Lipid Metabolism ◽  
Brown Adipose

Exposure to cold alters glucose and lipid metabolism of white and brown adipose tissue via activation of β-adrenergic receptor (ADRB). Fibroblast growth factor 21 (FGF21) has been shown to be locally released from adipose tissue upon activation of ADRBs and FGF21 increases glucose uptake in adipocytes. Therefore, FGF21 may play an autocrine role in inducing glucose uptake after β-adrenergic stimulation. To determine the putative autocrine role of FGF21, we stimulated three different types of adipocytes in vitro with Isoprenaline (Iso), an ADRB agonist, in the presence or absence of the FGF receptor (FGFR) inhibitor PD 173074. The three cell lines represent white (3T3-L1), beige (ME3) and brown (WT-1) adipocyte phenotypes, respectively. All three cells systems expressed β-klotho (KLB) and FGFR1 after differentiation and treatment with recombinant FGF21 increased glucose uptake in 3T3-L1 and WT-1 adipocytes, while no significant effect was observed in ME3. Oppositely, all three cell lines responded to Iso treatment and an increase in glucose uptake and lipolysis were observed. Interestingly, in response to the Iso treatment only the WT-1 adipocytes showed an increase in FGF21 in the medium. This was consistent with the observation that PD 173074 decreased Iso-induced glucose uptake in the WT-1 adipocytes. This suggests that FGF21 plays an autocrine role and increases glucose uptake after β-adrenergic stimulation of cultured brown WT-1 adipocytes.

scholarly journals Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

2015 ◽  
pp. MCB.00722-15 ◽  
Author(s):  
Francisco Verdeguer ◽  
Meghan S. Soustek ◽  
Maximilian Hatting ◽  
Sharon M. Blättler ◽  
Devin McDonald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Brown Fat ◽  
Secreted Proteins ◽  
Fat Depots ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
White Fat

Mitochondrial oxidative and thermogenic function in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensate for partial deficiencies in this tissue and protect against obesity. Here, we show that the transcription factor YY1 in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins including FGF21, BMP8b, GDF15, Angptl6, Neuromedin B and Nesfatin linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity, exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight.

scholarly journals The Role of Brown Adipose Tissue Dysfunction in the Development of Cardiovascular Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Hong-Jin Chen ◽  
Ting Meng ◽  
Ping-Jin Gao ◽  
Cheng-Chao Ruan
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cardiovascular Health ◽  
Stromal Vascular Fraction ◽  
Protective Role ◽  
Vital Role ◽  
Brown Adipocytes ◽  
Glucose And Lipid Metabolism ◽  
Brown Adipose

Brown adipose tissue (BAT), consisted of brown adipocytes and stromal vascular fraction, which includes endothelial cells, lymphocytes, fibroblasts and stem cells, plays a vital role in regulating cardiovascular health and diseases. As a thermogenic organ, BAT can influence body through strengthening energy expenditure by promoting glucose and lipid metabolism. In addition, BAT is also an endocrine organ which is able to secret adipokines in an autocrine and/or paracrine fashion. BAT plays a protective role in cardiovascular system through attenuating cardiac remodeling and suppressing inflammatory response. In this review, we summarize the advances from the discovery of BAT to the present and provide an overview on the role of BAT dysfunction in cardiovascular diseases.

142-OR: Unique Role of the a4 Component for S6-Kinase Activity in Metabolic Regulation and Anti-apoptotic Effect in Brown Adipose Tissue

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 142-OR
Author(s):  
MASAJI SAKAGUCHI ◽  
SHOTA OKAGAWA ◽  
SAYAKA KITANO ◽  
TATSUYA KONDO ◽  
EIICHI ARAKI
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Metabolic Regulation ◽  
Kinase Activity ◽  
S6 Kinase ◽  
Unique Role ◽  
Brown Adipose ◽  
Apoptotic Effect

scholarly journals Effects of stem cells from inducible brown adipose tissue on diet-induced obesity in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Enrique Calvo ◽  
Noelia Keiran ◽  
Catalina Núñez-Roa ◽  
Elsa Maymó-Masip ◽  
Miriam Ejarque ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Therapeutic Option ◽  
Metabolic Activation ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Obesity In Mice ◽  
Treatment Of Obesity ◽  
Visceral Adipose

AbstractAdipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

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