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human adipocyte obesity

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https://www.readbyqxmd.com/read/29666371/integration-of-human-adipocyte-chromosomal-interactions-with-adipose-gene-expression-prioritizes-obesity-related-genes-from-gwas
#1
David Z Pan, Kristina M Garske, Marcus Alvarez, Yash V Bhagat, James Boocock, Elina Nikkola, Zong Miao, Chelsea K Raulerson, Rita M Cantor, Mete Civelek, Craig A Glastonbury, Kerrin S Small, Michael Boehnke, Aldons J Lusis, Janet S Sinsheimer, Karen L Mohlke, Markku Laakso, Päivi Pajukanta, Arthur Ko
Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression...
April 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29661866/reciprocal-effects-of-antiretroviral-drugs-used-to-treat-hiv-infection-on-the-fibroblast-growth-factor-21-%C3%AE-klotho-system
#2
Ricardo Moure, Pere Domingo, Joan Villarroya, Laura Gasa, José M Gallego-Escuredo, Tania Quesada-López, Samantha Morón-Ros, Alberto F Maroto, Gracia M Mateo, Joan C Domingo, Francesc Villarroya, Marta Giralt
Following antiretroviral therapy, HIV-infected patients show increased circulating levels of the antidiabetic hormone fibroblast growth factor-21 (FGF21). In contrast, expression of the FGF21-obligatory co-receptor β-Klotho (KLB) is reduced in target tissues. This situation is comparable to the FGF21 resistance status observed in obesity and type-2 diabetes. Here, we performed the first systematic study of the effects of distinct members of different antiretroviral drug classes on the FGF21/KLB system in human hepatic, adipose, and skeletal muscle cells...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29661693/phosphorylation-of-beta-3-adrenergic-receptor-at-serine-247-by-erk-map-kinase-drives-lipolysis-in-obese-adipocytes
#3
Shangyu Hong, Wei Song, Peter-James H Zushin, Bingyang Liu, Mark P Jedrychowski, Amir I Mina, Zhaoming Deng, Dimitrije Cabarkapa, Jessica A Hall, Colin J Palmer, Hassan Aliakbarian, John Szpyt, Steven P Gygi, Ali Tavakkoli, Lydia Lynch, Norbert Perrimon, Alexander S Banks
OBJECTIVE: The inappropriate release of free fatty acids from obese adipose tissue stores has detrimental effects on metabolism, but key molecular mechanisms controlling FFA release from adipocytes remain undefined. Although obesity promotes systemic inflammation, we find activation of the inflammation-associated Mitogen Activated Protein kinase ERK occurs specifically in adipose tissues of obese mice, and provide evidence that adipocyte ERK activation may explain exaggerated adipose tissue lipolysis observed in obesity...
March 29, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29656108/epoxygenase-inactivation-exacerbates-diet-and-aging-associated-metabolic-dysfunction-resulting-from-impaired-adipogenesis
#4
Antoni Olona, Ximena Terra, Jeong-Hun Ko, Carme Grau-Bové, Montserrat Pinent, Anna Ardevol, Ana Garcia Diaz, Aida Moreno-Moral, Matthew Edin, David Bishop-Bailey, Darryl C Zeldin, Timothy J Aitman, Enrico Petretto, Mayte Blay, Jacques Behmoaras
OBJECTIVE: When molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream enzymatic cascades, such as cyclooxygenase, in adipogenesis is well established. The exact contribution of the P450 epoxygenase pathway, however, remains to be established. Enzymes belonging to this pathway are mainly encoded by the CYP2J locus which shows extensive allelic expansion in mice. Here we aimed to establish the role of endogenous epoxygenase during adipogenesis under homeostatic and metabolic stress conditions...
March 9, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29653259/bisphenol-a-and-its-derivatives-decrease-expression-of-chemerin-which-reverses-its-stimulatory-action-in-ovarian-cancer-cells
#5
Marta Hoffmann, Agnieszka Rak, Anna Ptak
Chemerin is an adipocyte-secreted protein that associates with obesity, inflammation, metabolic dysfunction, and carcinogenesis. Previous studies have shown human granulosa cells to produce bioactive chemerin and its receptor CMKLR1. In the present study, we demonstrated that the mRNA level of chemerin receptor is higher in a granulosa cell tumor cell line than in epithelial cancer cells, whereas chemerin expression and secretion were lower. Various exogenous factors, such as bisphenol A and its halogenated derivatives tetrabromobisphenol A and tetrachlorobisphenol A, can affect adipokine expression...
April 10, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29650791/impairments-in-adipose-tissue-microcirculation-in-type-2-diabetes-mellitus-assessed-by-real-time-contrast-enhanced-ultrasound
#6
Donghua Hu, Devika Remash, Ryan D Russell, Timothy Greenaway, Stephen Rattigan, Kathryn A Squibb, Graeme Jones, Dino Premilovac, Stephen M Richards, Michelle A Keske
BACKGROUND: In obesity and type 2 diabetes mellitus (T2D), adipose tissue expansion (because of larger adipocytes) results in reduced microvascular density which is thought to lead to adipocyte hypoxia, inflammation, and reduced nutrient delivery to the adipocyte. Adipose tissue microvascular responses in humans with T2D have not been extensively characterized. Furthermore, it has not been determined whether impaired microvascular responses in human adipose tissue are most closely associated with adiposity, inflammation, or altered metabolism...
April 2018: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/29650773/cannabinoid-type-1-receptors-are-upregulated-during-acute-activation-of-brown-adipose-tissue
#7
Minna Lahesmaa, Olof Eriksson, Thorsten Gnad, Vesa Oikonen, Marco Bucci, Jussi Hirvonen, Kalle Koskensalo, Jarmo Teuho, Tarja Niemi, Markku Taittonen, Salla Lahdenpohja, Mueez U Din, Merja Haaparanta-Solin, Alexander Pfeifer, Kirsi A Virtanen, Pirjo Nuutila
Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans. Obesity is associated with up-regulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and decrease cardiometabolic risk factors. These effects may partly be mediated via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents. To investigate the significance of CB1R in BAT function, we quantified the density of CB1R in human and rodent BAT using the positron emission tomography (PET) radioligand [18 F]FMPEP- d 2 , and in parallel measured BAT activation with the glucose analogue [18 F]FDG...
April 12, 2018: Diabetes
https://www.readbyqxmd.com/read/29643769/the-role-of-physical-exercise-to-improve-the-browning-of-white-adipose-tissue-via-pomc-neurons
#8
REVIEW
Kellen C da Cruz Rodrigues, Rodrigo M Pereira, Thaís D P de Campos, Rodrigo F de Moura, Adelino S R da Silva, Dennys E Cintra, Eduardo R Ropelle, José R Pauli, Michel B de Araújo, Leandro P de Moura
Obesity is a public health issue that affects more than 600 million adults worldwide. The disease is characterized by fat accumulation, mainly in the abdominal area. The human body is mainly composed of two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT); however, the browning process generates a different type of brown fat-like adipocyte in WAT, which similar to BAT has thermogenic capacity by activating UCP-1. The hypothalamic arcuate nucleus plays an important role in WAT browning via POMC neurons, which are influenced by synergistic insulin and leptin signaling...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29626186/de-novo-reconstruction-of-human-adipose-transcriptome-reveals-conserved-lncrnas-as-regulators-of-brown-adipogenesis
#9
Chunming Ding, Yen Ching Lim, Sook Yoong Chia, Arcinas Camille Esther Walet, Shaohai Xu, Kinyui Alice Lo, Yanling Zhao, Dewen Zhu, Zhihui Shan, Qingfeng Chen, Melvin Khee-Shing Leow, Dan Xu, Lei Sun
Obesity has emerged as an alarming health crisis due to its association with metabolic risk factors such as diabetes, dyslipidemia, and hypertension. Recent work has demonstrated the multifaceted roles of lncRNAs in regulating mouse adipose development, but their implication in human adipocytes remains largely unknown. Here we present a catalog of 3149 adipose active lncRNAs, of which 909 are specifically detected in brown adipose tissue (BAT) by performing deep RNA-seq on adult subcutaneous, omental white adipose tissue and fetal BATs...
April 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29617644/a-transcriptional-circuit-filters-oscillating-circadian-hormonal-inputs-to-regulate-fat-cell-differentiation
#10
Zahra Bahrami-Nejad, Michael L Zhao, Stefan Tholen, Devon Hunerdosse, Karen E Tkach, Sabine van Schie, Mingyu Chung, Mary N Teruel
Glucocorticoid and other adipogenic hormones are secreted in mammals in circadian oscillations. Loss of this circadian oscillation pattern correlates with obesity in humans, raising the intriguing question of how hormone secretion dynamics affect adipocyte differentiation. Using live, single-cell imaging of the key adipogenic transcription factors CEBPB and PPARG, endogenously tagged with fluorescent proteins, we show that pulsatile circadian hormone stimuli are rejected by the adipocyte differentiation control system...
April 3, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29606342/what-can-brown-ing-do-for-you
#11
REVIEW
Amar M Singh, Stephen Dalton
Human stem cell-based models of thermogenic adipocytes provide an opportunity for the establishment of new therapeutics, modeling of disease mechanisms, and understanding of development. Pluripotent stem cells, adipose-derived stem cells/preadipocytes, and programming-reprogramming-based approaches have been used to develop cell-based platforms for drug screening and transplantable therapeutics in the metabolic disease arena. Here we provide a detailed overview of these approaches, the latest advances in this field, and the opportunities and shortcomings they present...
March 29, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29605715/a-computational-biology-approach-of-a-genome-wide-screen-connected-mirnas-to-obesity-and-type-2-diabetes
#12
Pascal Gottmann, Meriem Ouni, Sophie Sausenthaler, Julian Roos, Laura Stirm, Markus Jähnert, Anne Kamitz, Nicole Hallahan, Wenke Jonas, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger, Matthias Blüher, Pamela Fischer-Posovszky, Heike Vogel, Annette Schürmann
OBJECTIVE: Obesity and type 2 diabetes (T2D) arise from the interplay between genetic, epigenetic, and environmental factors. The aim of this study was to combine bioinformatics and functional studies to identify miRNAs that contribute to obesity and T2D. METHODS: A computational framework (miR-QTL-Scan) was applied by combining QTL, miRNA prediction, and transcriptomics in order to enhance the power for the discovery of miRNAs as regulative elements. Expression of several miRNAs was analyzed in human adipose tissue and blood cells and miR-31 was manipulated in a human fat cell line...
March 15, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29593245/evaluation-and-optimization-of-differentiation-conditions-for-human-primary-brown-adipocytes
#13
XingYun Wang, LiangHui You, XianWei Cui, Yun Li, Xing Wang, PengFei Xu, LiJun Zhu, Juan Wen, LingXia Pang, XiRong Guo, ChenBo Ji
As an effective way to improve energy expenditure, increasing the mass and activity of brown adipose tissue (BAT) has become a promising treatment for obesity and its associated disorders. Many efforts have been made to promote brown adipogenesis and increase the thermogenic capacity of brown adipose cells (BACs). The present culture schemes for human BAC differentiation are mostly derived from white adipocyte differentiation schemes. To solve this issue, we compared the adipogenic and thermogenic effects of various components on human BAC differentiation and optimized their concentrations as well as the culture time for BAC differentiation...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29580847/parabens-and-measures-of-adiposity-among-adults-and-children-from-the-u-s-general-population-nhanes-2007-2014
#14
Lesliam Quirós-Alcalá, Jessie P Buckley, Meleah Boyle
BACKGROUND: Emerging experimental studies suggest that parabens could affect metabolism by altering the microbiome or signaling pathways involved in adipocyte differentiation. While human exposure to parabens is widespread, epidemiologic studies assessing the role of these chemicals on adiposity measures are scarce. OBJECTIVE: We examined associations of parabens with adiposity measures among adults and children in the U.S. general population. METHODS: We conducted covariate-adjusted linear and logistic regression models to examine associations between urinary biomarker concentrations of four parabens (butyl-BP, ethyl-EP, methyl-MP, and propyl paraben-PP) and measures of adiposity (obesity; body mass index, BMI or BMI z-score; and waist circumference) among 4730 adults (2007-2014) and 1324 children (2007-2012), participating in the National Health and Nutrition Examination Survey...
March 15, 2018: International Journal of Hygiene and Environmental Health
https://www.readbyqxmd.com/read/29580841/long-non-coding-rnas-associated-with-metabolic-traits-in-human-white-adipose-tissue
#15
Hui Gao, Alastair Kerr, Hong Jiao, Chung-Chau Hon, Mikael Rydén, Ingrid Dahlman, Peter Arner
Long non-coding RNAs (lncRNAs) belong to a recently discovered class of molecules proposed to regulate various cellular processes. Here, we systematically analyzed their expression in human subcutaneous white adipose tissue (WAT) and found that a limited set was differentially expressed in obesity and/or the insulin resistant state. Two lncRNAs herein termed adipocyte-specific metabolic related lncRNAs, ASMER-1 and ASMER-2 were enriched in adipocytes and regulated by both obesity and insulin resistance. Knockdown of either ASMER-1 or ASMER-2 by antisense oligonucleotides in in vitro differentiated human adipocytes revealed that both genes regulated adipogenesis, lipid mobilization and adiponectin secretion...
March 15, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29578525/characterization-of-immune-cells-in-human-adipose-tissue-by-using-flow-cytometry
#16
Suzan Wetzels, Mitchell Bijnen, Erwin Wijnands, Erik A L Biessen, Casper G Schalkwijk, Kristiaan Wouters
Infiltration of immune cells in the subcutaneous and visceral adipose tissue (AT) deposits leads to a low-grade inflammation contributing to the development of obesity-associated complications such as type 2 diabetes. To quantitatively and qualitatively investigate the immune cell subsets in human AT deposits, we have developed a flow cytometry approach. The stromal vascular fraction (SVF), containing the immune cells, is isolated from subcutaneous and visceral AT biopsies by collagenase digestion. Adipocytes are removed after centrifugation...
March 6, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29559978/human-body-composition-and-immunity-visceral-adipose-tissue-produces-il-15-and-muscle-strength-inversely-correlates-with-nk-cell-function-in-elderly-humans
#17
Ahmad Al-Attar, Steven R Presnell, Jody L Clasey, Douglas E Long, R Grace Walton, Morgan Sexton, Marlene E Starr, Philip A Kern, Charlotte A Peterson, Charles T Lutz
Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections and cancers, but these crucial activities decline with age. NK cell development, homeostasis, and function require IL-15 and its chaperone, IL-15 receptor alpha (IL-15Rα). Macrophages and dendritic cells (DC) are major sources of these proteins. We had previously postulated that additional IL-15 and IL-15Rα is made by skeletal muscle and adipose tissue. These sources may be important in aging, when IL-15-producing immune cells decline...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29555462/effects-of-tunable-3d-bioprinted-hydrogels-on-human-brown-adipocyte-behavior-and-metabolic-function
#18
Mitchell Kuss, Jiyoung Kim, Dianjun Qi, Shaohua Wu, Yuguo Lei, Soonkyu Chung, Bin Duan
Obesity and its related health complications cause billions of dollars in healthcare costs annually in the United States, and there are yet to be safe and long-lasting anti-obesity approaches. Using brown adipose tissue (BAT) is a promising approach, as it uses fats for energy expenditure. However, the effect of the microenvironment on human thermogenic brown adipogenesis and how to generate clinically relevant sized and functioning BAT are still unknown. In our current study, we evaluated the effects of endothelial growth medium exposure on brown adipogenesis of human brown adipose progenitors (BAP)...
March 16, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29554135/thermogenic-capacity-of-human-periaortic-adipose-tissue-is-transformed-by-body-weight
#19
Diana Vargas, Carolina López, Edward Acero, Edgar Benitez, Angélica Wintaco, Jaime Camacho, Marisol Carreño, Juan Umaña, Daniela Jimenez, Said Díaz, Fernando Lizcano
The anatomical location of adipose tissue might have direct implications for its functionality and risk of cardiovascular disease. Adipose tissue surrounding blood vessels may be thermogenically more active in specific areas of the body, releasing substances that regulate vascular metabolism. In humans, the phenotypic characteristics of adipose tissue surrounding the aorta and the cardiovascular disease risk that it might entail remain largely unknown. Here, we compared thermogenesis-related molecular features of human periaortic adipose tissue samples with those of subcutaneous adipose tissue, obtained by sternotomy from 42 patients undergoing cardiovascular surgery...
2018: PloS One
https://www.readbyqxmd.com/read/29549282/abdominal-subcutaneous-and-visceral-adipocyte-size-lipolysis-and-inflammation-relate-to-insulin-resistance-in-male-obese-humans
#20
K Verboven, K Wouters, K Gaens, D Hansen, M Bijnen, S Wetzels, C D Stehouwer, G H Goossens, C G Schalkwijk, E E Blaak, J W Jocken
Obesity is associated with a disturbed adipose tissue (AT) function characterized by adipocyte hypertrophy, an impaired lipolysis and pro-inflammatory phenotype, which contributes to insulin resistance (IR). We investigated whether AT phenotype in different AT depots of obese individuals with and without type 2 diabetes mellitus (T2DM) is associated with whole-body IR. Subcutaneous (SC) and visceral (V) AT biopsies from 18 lean, 17 obese and 8 obese T2DM men were collected. AT phenotype was characterized by ex vivo measurement of basal and stimulated lipolysis (mature adipocytes), adipocyte size distribution (AT tissue sections) and AT immune cells (flow cytometry)...
March 16, 2018: Scientific Reports
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