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human adipocyte obesity

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https://www.readbyqxmd.com/read/28436964/swell1-is-a-regulator-of-adipocyte-size-insulin-signalling-and-glucose-homeostasis
#1
Yanhui Zhang, Litao Xie, Susheel K Gunasekar, Dan Tong, Anil Mishra, William J Gibson, Chuansong Wang, Trevor Fidler, Brodie Marthaler, Aloysius Klingelhutz, E Dale Abel, Isaac Samuel, Jessica K Smith, Lei Cao, Rajan Sah
Adipocytes undergo considerable volumetric expansion in the setting of obesity. It has been proposed that such marked increases in adipocyte size may be sensed via adipocyte-autonomous mechanisms to mediate size-dependent intracellular signalling. Here, we show that SWELL1 (LRRC8a), a member of the Leucine-Rich Repeat Containing protein family, is an essential component of a volume-sensitive ion channel (VRAC) in adipocytes. We find that SWELL1-mediated VRAC is augmented in hypertrophic murine and human adipocytes in the setting of obesity...
April 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28425849/age-dependent-obesity-and-mitochondrial-dysfunction
#2
Qilong Oscar Yang Li, Ines Soro-Arnaiz, Julián Aragonés
Aging is associated with progressive visceral white adipose tissue (WAT) expansion both in human and mouse. Importantly, WAT enlargement is initiated early in life, suggesting that molecular mechanisms underlying age-dependent obesity are activated at early stages of lifetime. Our recent study found that age-dependent obesity was associated with a specific decline in mitochondrial complex IV activity, which leads to reduced fatty acid oxidation and subsequent adipocyte hypertrophy. At the molecular level, global mitochondrial complex IV inhibition was driven by hypoxia-inducible factor-1α (HIF1α)-mediated repression of some of its key subunits, including cytochrome c oxidase 5b (Cox5b)...
March 15, 2017: Adipocyte
https://www.readbyqxmd.com/read/28425848/the-contribution-of-bone-marrow-derived-cells-to-the-human-adipocyte-pool
#3
Peter Arner, Mikael Rydén
White adipose tissue is a remarkably expandable organ with results in the last decade showing that human white adipocytes are continuously turned over during the entire life-span. Data primarily in murine models have demonstrated that adipocytes are derived from precursors present mainly in the perivascular areas of adipose tissue but their precise origin remains unclear. Subsets of cells present in bone marrow display a multipotent differentiation capacity which has prompted the hypothesis that bone marrow-derived cells (BMDCs) may also contribute to the adipocyte pool present in peripheral fat depots...
March 15, 2017: Adipocyte
https://www.readbyqxmd.com/read/28425845/nck2-an-unexpected-regulator-of-adipogenesis
#4
N Haider, J Dusseault, A Rudich, L Larose
The regulation of adipose tissue expansion by adipocyte hypertrophy and/or hyperplasia is the topic of extensive investigations given the potential differential contribution of the 2 processes to the development of numerous chronic diseases associated with obesity. We recently discovered that the loss-of-function of the Src homology domain-containing protein Nck2 in mice promotes adiposity accompanied with adipocyte hypertrophy and impaired function, and enhanced adipocyte differentiation in vitro. Moreover, in severely-obese human's adipose tissue, we found that Nck2 expression is markedly downregulated...
February 6, 2017: Adipocyte
https://www.readbyqxmd.com/read/28420164/the-angiogenesis-inhibitor-als-l1023-from-lemon-balm-leaves-attenuates-high-fat-diet-induced-nonalcoholic-fatty-liver-disease-through-regulating-the-visceral-adipose-tissue-function
#5
Jeongjun Kim, Haerim Lee, Jonghoon Lim, Jaeho Oh, Soon Shik Shin, Michung Yoon
Similar to neoplastic tissues, growth and development of adipose tissue are thought to be angiogenesis-dependent. Since visceral adipose tissue (VAT) is associated with development and progression of nonalcoholic fatty liver disease (NAFLD), we hypothesized that angiogenesis inhibition would attenuate obesity-induced NAFLD. We fed C57BL/6J mice a low-fat diet (LFD, chow 10% kcal fat), a high-fat diet (HFD, 45% kcal fat) or HFD supplemented with the lemon-balm extract ALS-L1023 (HFD-ALS) for 15 weeks. ALS-L1023 reduced endothelial cell-tube formation in vitro...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28418430/wat-on-a-chip-a-physiologically-relevant-microfluidic-system-incorporating-white-adipose-tissue
#6
Peter Loskill, Thiagarajan Sezhian, Kevin M Tharp, Felipe T Lee-Montiel, Shaheen Jeeawoody, Willie Mae Reese, Peter-James H Zushin, Andreas Stahl, Kevin E Healy
Organ-on-a-chip systems possess a promising future as drug screening assays and as testbeds for disease modeling in the context of both single-organ systems and multi-organ-chips. Although it comprises approximately one fourth of the body weight of a healthy human, an organ frequently overlooked in this context is white adipose tissue (WAT). WAT-on-a-chip systems are required to create safety profiles of a large number of drugs due to their interactions with adipose tissue and other organs via paracrine signals, fatty acid release, and drug levels through sequestration...
April 18, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28416283/activation-of-irf1-in-human-adipocytes-leads-to-phenotypes-associated-with-metabolic-disease
#7
Max Friesen, Raymond Camahort, Youn-Kyoung Lee, Fang Xia, Robert E Gerszten, Eugene P Rhee, Rahul C Deo, Chad A Cowan
The striking rise of obesity-related metabolic disorders has focused attention on adipocytes as critical mediators of disease phenotypes. To better understand the role played by excess adipose in metabolic dysfunction it is crucial to decipher the transcriptional underpinnings of the low-grade adipose inflammation characteristic of diseases such as type 2 diabetes. Through employing a comparative transcriptomics approach, we identified IRF1 as differentially regulated between primary and in vitro-derived genetically matched adipocytes...
April 5, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28414311/a-self-sustained-loop-of-inflammation-driven-inhibition-of-beige-adipogenesis-in-obesity
#8
Kyoung-Jin Chung, Antonios Chatzigeorgiou, Matina Economopoulou, Ruben Garcia-Martin, Vasileia I Alexaki, Ioannis Mitroulis, Marina Nati, Janine Gebler, Tjalf Ziemssen, Susan E Goelz, Julia Phieler, Jong-Hyung Lim, Katia P Karalis, Thalia Papayannopoulou, Matthias Blüher, George Hajishengallis, Triantafyllos Chavakis
In obesity, inflammation of white adipose tissue (AT) is associated with diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic and energy-dissipating function mediated by beige adipocytes that express the uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory mechanism of beige adipogenesis in obesity that required direct adhesive interactions between macrophages and adipocytes mediated by the integrin α4 and its counter-receptor VCAM-1, respectively; expression of the latter was upregulated in obesity...
April 17, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28414093/imbalance-in-leptin-adiponectin-levels-and-leptin-receptor-expression-as-chief-contributors-to-triple-negative-breast-cancer-progression-in-northeast-india
#9
Rizwana Sultana, Amal Ch Kataki, Bibhuti Bhusan Borthakur, Tarun K Basumatary, Sujoy Bose
BACKGROUND: Triple-Negative breast cancer (TNBC), accounts for a large percentage of breast cancer cases in India including Northeast India. TNBC has an unclear molecular aetiology and hence limited targeted therapies. Human breast is comprised of glandular, ductal, connective, and adipose tissues. Adipose tissue is composed of adipocytes. The adipocytes apart from being energy storage depots, are also active sources of adipocytokines and/or adipokines. The role of adipokines in breast cancer including TNBC has been sporadically documented...
April 14, 2017: Gene
https://www.readbyqxmd.com/read/28412522/small-non-coding-rnas-in-adipocyte-biology-and-obesity
#10
REVIEW
Ez-Zoubir Amri, Marcel Scheideler
Obesity has reached epidemic proportions world-wide and constitutes a substantial risk factor for hypertension, type 2 diabetes, cardiovascular diseases and certain cancers. So far, regulation of energy intake by dietary and pharmacological treatments has met limited success. The main interest of current research is focused on understanding the role of different pathways involved in adipose tissue function and modulation of its mass. Whole-genome sequencing studies revealed that the majority of the human genome is transcribed, with thousands of non-protein-coding RNAs (ncRNA), which comprise small and long ncRNAs...
April 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28406693/polychlorinated-biphenyl-153-in-lipid-medium-modulates-differentiation-of-human-adipocytes
#11
D Mullerova, M Pesta, J Dvorakova, M Cedikova, V Kulda, P Dvorak, V Bouchalová, M Kralickova, V Babuska, J Kuncova, J Langmajerova, L Muller
Emerging evidence indicates that polychlorinated biphenyls (PCBs) are involved in the development of diabetes mellitus in the obese. The purpose of this study was to determine mechanisms by which PCB 153 (2,2´,4,4´,5,5´-hexachlorobiphenyl) could influence diet-induced obesity and insulin resistance during adipogenesis. Lineage of h-ADMSCs was differentiated either as control (differentiation medium only), or with lipid vehicle modelling high fat nutrition (NuTRIflex) or lipid free vehicle (dimethylsulfoxide) for 28 days with or without PCB 153 daily co-exposure (in three concentrations 0...
April 12, 2017: Physiological Research
https://www.readbyqxmd.com/read/28391908/apob-lipoproteins-and-dysfunctional-white-adipose-tissue-relation-to-risk-factors-for-type-2-diabetes-in-humans
#12
Valérie Lamantia, Simon Bissonnette, Hanny Wassef, Yannick Cyr, Alexis Baass, Robert Dufour, Rémi Rabasa-Lhoret, May Faraj
BACKGROUND: Elevated plasma apoB is an independent predictor of T2D; however, underlying mechanisms remain unclear. Chronic reduction in white adipose tissue (WAT) function promotes T2D. We reported that differentiation of preadipocytes and acute incubation of human WAT with LDL induce their dysfunction (decreased hydrolysis and storage of triglyceride-rich lipoproteins [TRL]). OBJECTIVE: To examine the hypothesis that the association of plasma apoB with T2D risk factors, hypertriglyceridemia (hyperTG), insulin resistance (IR), and hyperinsulinemia, was dependent on WAT dysfunction...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28382382/sucnr1-mediated-chemotaxis-of-macrophages-aggravates-obesity-induced-inflammation-and-diabetes
#13
Janna A van Diepen, Joris H Robben, Guido J Hooiveld, Claudia Carmone, Mohammad Alsady, Lily Boutens, Melissa Bekkenkamp-Grovenstein, Anneke Hijmans, Udo F H Engelke, Ron A Wevers, Mihai G Netea, Cees J Tack, Rinke Stienstra, Peter M T Deen
AIMS/HYPOTHESIS: Obesity induces macrophages to drive inflammation in adipose tissue, a crucial step towards the development of type 2 diabetes. The tricarboxylic acid (TCA) cycle intermediate succinate is released from cells under metabolic stress and has recently emerged as a metabolic signal induced by proinflammatory stimuli. We therefore investigated whether succinate receptor 1 (SUCNR1) could play a role in the development of adipose tissue inflammation and type 2 diabetes. METHODS: Succinate levels were determined in human plasma samples from individuals with type 2 diabetes and non-diabetic participants...
April 5, 2017: Diabetologia
https://www.readbyqxmd.com/read/28373675/grape-seed-proanthocyanidin-supplementation-reduces-adipocyte-size-and-increases-adipocyte-number-in-obese-rats
#14
A Pascual-Serrano, A Arola-Arnal, S Suárez-Garcia, F I Bravo, M Suárez, L Arola, C Bladé
OBJECTIVES: White adipose tissue (WAT) expands through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been associated with insulin resistance and dyslipidemia independently of body composition and fat distribution. In contrast, hyperplasia protects against metabolic alterations. Proanthocyanidins, which are the most abundant flavonoids in the human diet, improve metabolic disturbances associated with diet-induced obesity without reducing body weight or adiposity...
April 4, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28363697/polymorphisms-and-mutations-in-the-melanocortin-3-receptor-and-their-relation-to-human-obesity
#15
REVIEW
Andrew P Demidowich, Joo Yun Jun, Jack A Yanovski
Inactivating mutations in the melanocortin 3 receptor (Mc3r) have been described as causing obesity in mice, but the physiologic effects of MC3R mutations in humans have been less clear. Here we review the MC3R polymorphisms and mutations identified in humans, and the in vitro, murine, and human cohort studies examining their putative effects. Some, but not all, studies suggest that the common human MC3R variant T6K+V81I, as well as several other rare, function-altering mutations, are associated with greater adiposity and hyperleptinemia with altered energy partitioning...
March 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28359093/diabetes-specific-regulation-of-adipocyte-metabolism-by-the-adipose-tissue-extracellular-matrix
#16
Nicki A Baker, Lindsey A Muir, Alexandra R Washabaugh, Christopher K Neeley, Sophie Yu-Pu Chen, Carmen G Flesher, John Vorwald, Jonathan F Finks, Amir A Ghaferi, Michael W Mulholland, Oliver A Varban, Carey N Lumeng, Robert W O'Rourke
Context: The role of the extracellular matrix (ECM) in regulating adipocyte metabolism in the context of metabolic disease is poorly defined. Objective: The objective of this study was to define the metabolic phenotype of adipocytes associated with human diabetes (DM) and the role of the ECM in regulating adipocyte metabolism. Design: Adipose tissues from obese patients were studied in standard 2-dimensional (2D) cell culture and an in vitro model of decellularized adipose tissue ECM repopulated with human adipocytes, and results were correlated with DM status...
March 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28357654/human-adipocyte-differentiation-and-characterization-in-a-perfusion-based-cell-culture-device
#17
Yunxiao Liu, Patthara Kongsuphol, Sajay Bhuvanendran Nair Gourikutty, Qasem Ramadan
Adipocytes have gained significant attention recently, because they are not only functioning as energy storage but also as endocrine cells. Adipocytes secret various signaling molecules, including adiponectin, MCP-1, and IL-6, termed collectively as "adipokines". Adipokines regulate glucose metabolism, thereby play an important role in obesity, diabetes type 2, and other metabolic disorders. Conventionally, to study the secretory function, adipocytes are cultured in vitro in static conditions. However, static culturing condition falls short of mimicking the interstitial fluid flows in living systems...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28356429/enrichment-of-triglyceride-rich-lipoproteins-with-apolipoprotein-c-i-is-positively-associated-with-their-delayed-plasma-clearance-independently-of-other-transferable-apolipoproteins-in-postmenopausal-overweight-and-obese-women
#18
Hanny Wassef, Simon Bissonnette, Robert Dufour, Jean Davignon, May Faraj
Background: The role of plasma apolipoprotein (apo) C-I in cardiometabolic risk in humans is unclear. However, in vitro studies showed a dual role for apoC-I, both protective and harmful, depending on the carrier lipoprotein.Objective: We tested the hypothesis that triglyceride (TG)-rich lipoprotein (TRL) apoC-I, not total or HDL apoC-I, is associated with delayed postprandial plasma clearance of TRLs, independently of apoC-II, apoC-III, and apoE.Methods: This cross-sectional study examines the plasma clearance of a (13)C-triolein-labeled high-fat meal (68% fat energy) in 20 postmenopausal overweight and obese women [body mass index (in kg/m(2)) ≥27; aged 45-74 y] as the increment change in area under the 6-h postprandial curves (iAUC6h) of TRL parameters...
March 29, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28351837/cyclin-c-regulates-adipogenesis-by-stimulating-transcriptional-activity-of-ccaat-enhancer-binding-protein-alpha
#19
Ziyi Song, Alus M Xiaoli, Quanwei Zhang, Yi Zhang, Ellen S T Yang, Sven Wang, Rui Chang, Zhengdong D Zhang, Gongshe Yang, Randy Strich, Jeffrey E Pessin, Fajun Yang
Brown adipose tissue (BAT) is important for maintaining energy homeostasis and adaptive thermogenesis in rodents and humans. As disorders arising from dysregulated energy metabolism, such as obesity and metabolic diseases, have increased, so has interest in the molecular mechanisms in adipocyte biology. Using a functional screen, we identified cyclin C (CycC), a conserved subunit of the Mediator complex, as a novel regulator for brown adipocyte formation. siRNA-mediated CycC knockdown (KD) in brown preadipocytes impaired the early transcriptional program of differentiation, and genetic knockout (KO) of CycC completely blocked the differentiation process...
March 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28346411/the-cold-induced-lipokine-12-13-dihome-promotes-fatty-acid-transport-into-brown-adipose-tissue
#20
Matthew D Lynes, Luiz O Leiria, Morten Lundh, Alexander Bartelt, Farnaz Shamsi, Tian Lian Huang, Hirokazu Takahashi, Michael F Hirshman, Christian Schlein, Alexandra Lee, Lisa A Baer, Francis J May, Fei Gao, Niven R Narain, Emily Y Chen, Michael A Kiebish, Aaron M Cypess, Matthias Blüher, Laurie J Goodyear, Gökhan S Hotamisligil, Kristin I Stanford, Yu-Hua Tseng
Brown adipose tissue (BAT) and beige adipose tissue combust fuels for heat production in adult humans, and so constitute an appealing target for the treatment of metabolic disorders such as obesity, diabetes and hyperlipidemia. Cold exposure can enhance energy expenditure by activating BAT, and it has been shown to improve nutrient metabolism. These therapies, however, are time consuming and uncomfortable, demonstrating the need for pharmacological interventions. Recently, lipids have been identified that are released from tissues and act locally or systemically to promote insulin sensitivity and glucose tolerance; as a class, these lipids are referred to as 'lipokines'...
March 27, 2017: Nature Medicine
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