The Experts below are selected from a list of 70935 Experts worldwide ranked by ideXlab platform
Hiroko Isoda - One of the best experts on this subject based on the ideXlab platform.
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increasing camp levels of preAdipocytes by cyanidin 3 glucoside treatment induces the formation of beige phenotypes in 3t3 l1 Adipocytes
Journal of Nutritional Biochemistry, 2017Co-Authors: Toshiya Matsukawa, Myra O Villareal, Hideko Motojima, Hiroko IsodaAbstract:Obesity is a serious health problem and a major risk factor for the onset of several diseases such as heart disease, diabetes, stroke and cancer. The conversion of white Adipocytes to brown-like Adipocytes, also called beige or brite Adipocytes, by pharmacological and dietary compounds has gained attention as an effective treatment for obesity. Cyanidin-3-glucoside (Cy3G), a polyphenolic compound contained in black soybean, blueberry and grape, has several antiobesity effects. However, there are no reports on the role of Cy3G in the induction of differentiation of preAdipocytes to beige Adipocytes and corresponding phenotypes. Here, the formation of beige adipocyte phenotypes following treatment with Cy3G was evaluated using 3T3-L1 Adipocytes. Cy3G induced phenotypic changes to white Adipocytes, such as increased multilocular lipid droplets and mitochondrial content. Additionally, the expression of mitochondrial genes (TFAM, SOD2, UCP-1 and UCP-2), UCP-1 protein and beige adipocyte markers (CITED1 and TBX1) in 3T3-L1 Adipocytes was increased by Cy3G. Furthermore, Cy3G promoted preadipocyte differentiation by up-regulating of C/EBPβ through the elevation of the intracellular cAMP levels. These results indicated that Cy3G elevates the intracellular cAMP levels, which induces beige adipocyte phenotypes. This is the first report on the effect of Cy3G on induction of differentiation of preAdipocytes into beige adipocyte phenotypes.
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cyanidin 3 glucoside derived from black soybeans ameliorate type 2 diabetes through the induction of differentiation of preAdipocytes into smaller and insulin sensitive Adipocytes
Journal of Nutritional Biochemistry, 2015Co-Authors: Toshiya Matsukawa, Tetsuya Inaguma, Junkyu Han, Myra O Villareal, Hiroko IsodaAbstract:Black soybean is a health food has been reported to have antidiabetes effect. The onset of diabetes is closely associated with adipocyte differentiation, and at present, the effect of black soybean on adipocyte differentiation is unknown. Here, we investigated the antidiabetes effect of black soybean, and its anthocyanin cyanidin-3-glucoside (Cy3G), on adipocyte differentiation. Orally administered black soybean seed coat extract (BSSCE) reduced the body and white adipose tissue (WAT) weight of db/db mice accompanied by a decrease in the size of Adipocytes in WAT. Furthermore, 3T3-Ll cells treated with BSSCE and Cy3G were observed to differentiate into smaller Adipocytes which correlated with increased PPARγ and C/EBPα gene expressions, increased adiponectin secretion, decreased tumor necrosis factor-α secretion, activation of insulin signalling and increased glucose uptake. C2C12 myotubes cultured with conditioned medium, obtained from 3T3-L1 adipocyte cultures treated with Cy3G, also showed significantly increased expression of PGC-1α, SIRT1 and UCP-3 genes. Here we report that BSSCE, as well as its active compound Cy3G, has antidiabetes effects on db/db mice by promoting adipocyte differentiation. This notion is supported by BSSCE and Cy3G inducing the differentiation of 3T3-L1 preAdipocytes into smaller, insulin-sensitive Adipocytes, and it induced the activation of skeletal muscle metabolism. This is the first report on the modulation effect of Cy3G on adipocyte differentiation.
Joan Claria - One of the best experts on this subject based on the ideXlab platform.
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coordinate functional regulation between microsomal prostaglandin e synthase 1 mpges 1 and peroxisome proliferator activated receptor γ pparγ in the conversion of white to brown Adipocytes
Journal of Biological Chemistry, 2013Co-Authors: Veronica Garciaalonso, Cristina Lopezvicario, Esther Titos, Eva Moransalvador, Ana Gonzalezperiz, Bibiana Rius, Marcelina Parrizas, Oliver Werz, Vicente Arroyo, Joan ClariaAbstract:Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor and a master regulator of adipogenesis. Microsomal prostaglandin E (PGE) synthase-1 (mPGES-1) is an inducible enzyme that couples with cyclooxygenase-2 for the biosynthesis of PGE2. In this study we demonstrate the existence of a coordinate functional interaction between PPARγ and mPGES-1 in controlling the process of pre-adipocyte differentiation in white adipose tissue (WAT). Adipocyte-specific PPARγ knock-out mice carrying an aP2 promoter-driven Cre recombinase transgene showed a blunted response to the adipogenic effects of a high fat diet. Pre-Adipocytes from these knock-out mice showed loss of PPARγ and were resistant to rosiglitazone-induced WAT differentiation. In parallel, WAT from these mice showed increased expression of uncoupling protein 1, a mitochondrial enzyme that dissipates chemical energy as heat. Adipose tissue from mice lacking PPARγ also showed mPGES-1 up-regulation and increased PGE2 levels. In turn, PGE2 suppressed PPARγ expression and blocked rosiglitazone-induced pre-adipocyte differentiation toward white Adipocytes while directly elevating uncoupling protein 1 expression and pre-adipocyte differentiation into mature beige/brite Adipocytes. Consistently, pharmacological mPGES-1 inhibition directed pre-adipocyte differentiation toward white Adipocytes while suppressing differentiation into beige/brite Adipocytes. This browning effect was reproduced in knockdown experiments using a siRNA directed against mPGES-1. The effects of PGE2 on pre-adipocyte differentiation were not seen in mice lacking PPARγ in adipose tissue and were not mirrored by other eicosanoids (i.e. leukotriene B4). Taken together, these findings identify PGE2 as a key regulator of white-to-brown adipogenesis and suggest the existence of a coordinate regulation of adipogenesis between PPARγ and mPGES-1.
Chang Yeop Han - One of the best experts on this subject based on the ideXlab platform.
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adipocyte derived versican and macrophage derived biglycan control adipose tissue inflammation in obesity
Cell Reports, 2020Co-Authors: Chang Yeop Han, Christina K. Chan, Inkyung Kang, Ingrid A Harten, John A Gebe, Mohamed Omer, Kimberly M Alonge, Laura Den J Hartigh, Diego Gomes Kjerulf, Leela GoodspeedAbstract:Obesity is characterized by adipose tissue inflammation. Because proteoglycans regulate inflammation, here we investigate their role in adipose tissue inflammation in obesity. We find that adipose tissue versican and biglycan increase in obesity. Versican is produced mainly by Adipocytes and biglycan by adipose tissue macrophages. Both proteoglycans are also present in adipose tissue from obese human subjects undergoing gastric bypass surgery. Deletion of adipocyte-specific versican or macrophage-specific biglycan in mice reduces macrophage accumulation and chemokine and cytokine expression, although only adipocyte-specific versican deletion leads to sustained improvement in glucose tolerance. Macrophage-derived biglycan activates inflammatory genes in Adipocytes. Versican expression increases in cultured Adipocytes exposed to excess glucose, and adipocyte-conditioned medium stimulates inflammation in resident peritoneal macrophages, in part because of a versican breakdown product, versikine. These findings provide insights into the role of adipocyte- and macrophage-derived proteoglycans in adipose tissue inflammation in obesity.
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adipocyte specific deficiency of nadph oxidase 4 delays the onset of insulin resistance and attenuates adipose tissue inflammation in obesity
Arteriosclerosis Thrombosis and Vascular Biology, 2017Co-Authors: Laura Den J Hartigh, Mohamed Omer, Leela Goodspeed, Shari Wang, Tomasz Wietecha, Kevin D Obrien, Chang Yeop HanAbstract:Objective— Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, Adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown. Approach and Results— In this study, control C57BL/6 mice and mice in which NOX4 has been deleted specifically in Adipocytes were fed a high-fat, high-sucrose diet. During the development of obesity in control mice, adipocyte NOX4 and pentose phosphate pathway activity were transiently increased. Primary Adipocytes differentiated from mice with Adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with Adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged high-fat, high-sucrose feeding. Conclusions— These findings imply that NOX4-derived ROS may play a role in the onset of insulin resistance and adipose tissue inflammation. As such, therapeutics targeting NOX4-mediated ROS production could be effective in preventing obesity-associated conditions, such as insulin resistance.
Mengle Shao - One of the best experts on this subject based on the ideXlab platform.
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Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue
The Journal of clinical investigation, 2019Co-Authors: Anying Song, Mengle Shao, Hu Zhao, Wenting Dai, Min Jee Jang, Leonard Medrano, Jiayi Tan, Tinglu NingAbstract:Brown adipose tissue (BAT), as the main site of adaptive thermogenesis, exerts beneficial metabolic effects on obesity and insulin resistance. BAT has been previously assumed to contain a homogeneous population of brown Adipocytes. Utilizing multiple mouse models capable of genetically labeling different cellular populations, as well as single-cell RNA sequencing and 3D tissue profiling, we discovered a brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown Adipocytes within the BAT. Compared with the high-thermogenic brown Adipocytes, these low-thermogenic brown Adipocytes had substantially lower Ucp1 and Adipoq expression, larger lipid droplets, and lower mitochondrial content. Functional analyses showed that, unlike the high-thermogenic brown Adipocytes, the low-thermogenic brown Adipocytes have markedly lower basal mitochondrial respiration, and they are specialized in fatty acid uptake. Upon changes in environmental temperature, the 2 brown adipocyte subpopulations underwent dynamic interconversions. Cold exposure converted low-thermogenic brown Adipocytes into high-thermogenic cells. A thermoneutral environment had the opposite effect. The recruitment of high-thermogenic brown Adipocytes by cold stimulation is not affected by high-fat diet feeding, but it does substantially decline with age. Our results revealed a high degree of functional heterogeneity of brown Adipocytes.
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CM-Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program.pdf
2019Co-Authors: Mengle Shao, Jeff Ishibashi, Christine M. Kusminski, Chelsea Hepler, Lavanya Vishvanath, Karen A. Macpherson, Stephen B. Spurgin, Kai Sun, Qiong Wang, William HollandAbstract:The transcriptional regulators Ebf2 and Prdm16establish and maintain the brown and/or beige fatcell identity. However, the mechanisms operating inwhite Adipocytes to suppress the thermogenic geneprogram and maintain an energy-storing phenotypeare less understood. Here, we report that the transcriptionalregulator Zfp423 is critical for maintainingwhite adipocyte identity through suppression of thethermogenic gene program. Zfp423 expression isenriched in white versus brown Adipocytes and suppressedupon cold exposure. Doxycycline-inducibleinactivation of Zfp423 in mature Adipocytes, combinedwith b-adrenergic stimulation, triggers aconversion of differentiated adiponectin-expressinginguinal and gonadal Adipocytes into beige-like Adipocytes;this reprogramming event is sufficient toprevent and reverse diet-induced obesity and insulinresistance. Mechanistically, Zfp423 acts in Adipocytesto inhibit the activity of Ebf2 and suppressPrdm16 activation. These data identify Zfp423 as amolecular brake on adipocyte thermogenesis andsuggest a therapeutic strategy to unlock the thermogenicpotential of white Adipocytes in obesity.
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peroxisome proliferator activated receptor γ and its role in adipocyte homeostasis and thiazolidinedione mediated insulin sensitization
Molecular and Cellular Biology, 2018Co-Authors: Mengle Shao, Qiong A. Wang, Fang Zhang, Lei Jiang, Caroline Tao, Rana K Gupta, Philipp E SchererAbstract:Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, peroxisome proliferator-activated receptor γ (PPARγ) is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPARγ in mature Adipocytes in vivo Short-term PPARγ deficiency in Adipocytes reduces whole-body insulin sensitivity, but Adipocytes are viable both in vitro and in vivo However, after exposure to a high-fat diet, even short-term PPARγ deficiency leads to rapid adipocyte death. When mature Adipocytes are depleted of both PPARγ and CCAAT-enhancer-binding protein α (C/EBPα), they are rapidly depleted of lipids and undergo adipocyte death, both in vitro and in vivo Surprisingly, although thiazolidinediones (TZDs; PPARγ agonists) are thought to act mainly on PPARγ, PPARγ in Adipocytes is not required for the whole-body insulin-sensitizing effect of TZDs. This offers new mechanistic aspects of PPARγ/TZD action and its effect on whole-body metabolic homeostasis.
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Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program
Cell Metabolism, 2016Co-Authors: Mengle Shao, Jeff Ishibashi, Christine M. Kusminski, Qiong A. Wang, Chelsea Hepler, Lavanya Vishvanath, Karen A. Macpherson, Stephen B. Spurgin, Kai Sun, William L. HollandAbstract:The transcriptional regulators Ebf2 and Prdm16 establish and maintain the brown and/or beige fat cell identity. However, the mechanisms operating in white Adipocytes to suppress the thermogenic gene program and maintain an energy-storing phenotype are less understood. Here, we report that the transcriptional regulator Zfp423 is critical for maintaining white adipocyte identity through suppression of the thermogenic gene program. Zfp423 expression is enriched in white versus brown Adipocytes and suppressed upon cold exposure. Doxycycline-inducible inactivation of Zfp423 in mature Adipocytes, combined with β-adrenergic stimulation, triggers a conversion of differentiated adiponectin-expressing inguinal and gonadal Adipocytes into beige-like Adipocytes; this reprogramming event is sufficient to prevent and reverse diet-induced obesity and insulin resistance. Mechanistically, Zfp423 acts in Adipocytes to inhibit the activity of Ebf2 and suppress Prdm16 activation. These data identify Zfp423 as a molecular brake on adipocyte thermogenesis and suggest a therapeutic strategy to unlock the thermogenic potential of white Adipocytes in obesity.
Leela Goodspeed - One of the best experts on this subject based on the ideXlab platform.
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adipocyte derived versican and macrophage derived biglycan control adipose tissue inflammation in obesity
Cell Reports, 2020Co-Authors: Chang Yeop Han, Christina K. Chan, Inkyung Kang, Ingrid A Harten, John A Gebe, Mohamed Omer, Kimberly M Alonge, Laura Den J Hartigh, Diego Gomes Kjerulf, Leela GoodspeedAbstract:Obesity is characterized by adipose tissue inflammation. Because proteoglycans regulate inflammation, here we investigate their role in adipose tissue inflammation in obesity. We find that adipose tissue versican and biglycan increase in obesity. Versican is produced mainly by Adipocytes and biglycan by adipose tissue macrophages. Both proteoglycans are also present in adipose tissue from obese human subjects undergoing gastric bypass surgery. Deletion of adipocyte-specific versican or macrophage-specific biglycan in mice reduces macrophage accumulation and chemokine and cytokine expression, although only adipocyte-specific versican deletion leads to sustained improvement in glucose tolerance. Macrophage-derived biglycan activates inflammatory genes in Adipocytes. Versican expression increases in cultured Adipocytes exposed to excess glucose, and adipocyte-conditioned medium stimulates inflammation in resident peritoneal macrophages, in part because of a versican breakdown product, versikine. These findings provide insights into the role of adipocyte- and macrophage-derived proteoglycans in adipose tissue inflammation in obesity.
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adipocyte specific deficiency of nadph oxidase 4 delays the onset of insulin resistance and attenuates adipose tissue inflammation in obesity
Arteriosclerosis Thrombosis and Vascular Biology, 2017Co-Authors: Laura Den J Hartigh, Mohamed Omer, Leela Goodspeed, Shari Wang, Tomasz Wietecha, Kevin D Obrien, Chang Yeop HanAbstract:Objective— Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, Adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown. Approach and Results— In this study, control C57BL/6 mice and mice in which NOX4 has been deleted specifically in Adipocytes were fed a high-fat, high-sucrose diet. During the development of obesity in control mice, adipocyte NOX4 and pentose phosphate pathway activity were transiently increased. Primary Adipocytes differentiated from mice with Adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with Adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged high-fat, high-sucrose feeding. Conclusions— These findings imply that NOX4-derived ROS may play a role in the onset of insulin resistance and adipose tissue inflammation. As such, therapeutics targeting NOX4-mediated ROS production could be effective in preventing obesity-associated conditions, such as insulin resistance.
