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Adipocyte dysfunction

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https://www.readbyqxmd.com/read/28439091/abdominal-adiposity-intensifies-the-negative-effects-of-ambient-air-pollution-on-lung-function-in-korean-men
#1
H-J Kim, J-H Park, J-Y Min, K-B Min, Y-S Seo, J M Yun, H Kwon, J-I Kim, B Cho
BACKGROUND: Some studies have provided the possibility that adipose tissue may mediate air pollution-induced lung dysfunction. Studies using quantified fat mass data are needed to understand the biological mechanisms between adipocyte and air pollution in lung function. We aimed to investigate whether abdominal adiposity measured by computed tomography (CT) modifies the effects of air pollution on lung function in Korean men. METHODS: A total of 1876 men who visited one of two health checkup centers were recruited for this study...
April 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28437198/branched-chain-amino-acids-are-associated-with-insulin-resistance-independent-of-leptin-and-adiponectin-in-subjects-with-varying-degrees-of-glucose-tolerance
#2
Margery A Connelly, Justyna Wolak-Dinsmore, Robin P F Dullaart
BACKGROUND: Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the extent to which the association of BCAA with insulin resistance is attributable to altered leptin and adiponectin levels in individuals with varying degrees of glucose tolerance. METHODS: BCAA were measured by nuclear magnetic resonance, whereas leptin and adiponectin were measured by immunoassay, in subjects with normal fasting glucose (n = 30), impaired fasting glucose (n = 25), and T2DM (n = 15)...
February 21, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28425849/age-dependent-obesity-and-mitochondrial-dysfunction
#3
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/28424360/intermittent-hypoxia-in-obstructive-sleep-apnoea-mediates-insulin-resistance-through-adipose-tissue-inflammation
#4
Aoife M Murphy, Amandine Thomas, Sophie J Crinion, Brian D Kent, Murtaza M Tambuwala, Aurelie Fabre, Jean-Louis Pepin, Helen M Roche, Claire Arnaud, Silke Ryan
Obstructive sleep apnoea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but intermittent hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose tissue has been hypothesised to play a key role.We tested this hypothesis employing a comprehensive translational approach using a murine IH model of lean and diet-induced obese mice, an innovative IH system for cell cultures and a tightly controlled patient cohort.IH led to the development of insulin resistance in mice, corrected for the degree of obesity, and reduced insulin-mediated glucose uptake in 3T3-L1 adipocytes, associated with inhibition of the insulin-signalling pathway and downregulation of insulin-receptor substrate-1 mRNA...
April 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28420707/role-of-the-fatty-acid-binding-protein-4-in-heart-failure-and-cardiovascular-disease
#5
Ricardo Rodriguez-Calvo, Josefa Girona, Josep M Alegret, Alba Bosquet, Daiana Ibarretxe, Lluís Masana
Obesity and ectopic fat accumulation in non-adipose tissues are major contributors to heart failure (HF) and cardiovascular disease (CVD). Adipocytes act as endocrine organs by releasing a large number of bioactive molecules into the bloodstream, which participate in a communication network between white adipose tissue and other organs, including the heart. Among these molecules, fatty acid binding protein 4 (FABP4) has been recently shown to increase cardiometabolic risk. Both clinical and experimental evidence have identified FABP4 as a relevant player in atherosclerosis and coronary artery disease, and it has been directly related to cardiac alterations such as left ventricular hypertrophy (LVH) or both systolic and diastolic cardiac dysfunction...
April 18, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28416283/activation-of-irf1-in-human-adipocytes-leads-to-phenotypes-associated-with-metabolic-disease
#6
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/28414270/human-biallelic-mfn2-mutations-induce-mitochondrial-dysfunction-upper-body-adipose-hyperplasia-and-suppression-of-leptin-expression
#7
Nuno M Rocha, David A Bulger, Andrea Frontini, Hannah Titheradge, Sigrid Bjerge Gribsholt, Rachel Knox, Matthew Page, Julie Harris, Felicity Payne, Claire Adams, Alison Sleigh, John Crawford, Anette Prior Gjesing, Jette Bork-Jensen, Oluf Pedersen, Inês Barroso, Torben Hansen, Helen Cox, Mary Reilly, Alex Rossor, Rebecca J Brown, Simeon I Taylor, Duncan McHale, Martin Armstrong, Elif A Oral, Vladimir Saudek, Stephen I O'Rahilly, Eamonn R Maher, Bjørn Richelsen, David B Savage, Robert K Semple
MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes...
April 17, 2017: ELife
https://www.readbyqxmd.com/read/28408438/prdm16-represses-the-type-i-interferon-response-in-adipocytes-to-promote-mitochondrial-and-thermogenic-programing
#8
Megan Kissig, Jeff Ishibashi, Matthew J Harms, Hee-Woong Lim, Rachel R Stine, Kyoung-Jae Won, Patrick Seale
Brown adipose has the potential to counteract obesity, and thus, identifying signaling pathways that regulate the activity of this tissue is of great clinical interest. PRDM16 is a transcription factor that activates brown fat-specific genes while repressing white fat and muscle-specific genes in adipocytes. Whether PRDM16 also controls other gene programs to regulate adipocyte function was unclear. Here, we identify a novel role for PRDM16 in suppressing type I interferon (IFN)-stimulated genes (ISGs), including Stat1, in adipocytes in vitro and in vivo Ectopic activation of type I IFN signaling in brown adipocytes induces mitochondrial dysfunction and reduces uncoupling protein 1 (UCP1) expression...
April 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28404815/the-hepatokine-fgf21-is-crucial-for-peroxisome-proliferator-activated-receptor-%C3%AE-agonist-induced-amelioration-of-metabolic-disorders-in-obese-mice
#9
Tsuyoshi Goto, Mariko Hirata, Yumeko Aoki, Mari Iwase, Haruya Takahashi, Minji Kim, Yongjia Li, Huei-Fen Jheng, Wataru Nomura, Nobuyuki Takahashi, Chu-Sook Kim, Rina Yu, Shigeto Seno, Hideo Matsuda, Megumi Aizawa-Abe, Ken Ebihara, Nobuyuki Itoh, Teruo Kawada
Obesity causes excess fat accumulation in white adipose tissues (WAT) and also in other insulin-responsive organs such as the skeletal muscle, increasing the risk for insulin resistance, which can lead to obesity-related metabolic disorders. Peroxisome proliferator-activated receptor-α (PPARα) is a master regulator of fatty acid oxidation, whose activator is known to improve hyperlipidemia. However, the molecular mechanisms underlying PPARα activator-mediated reduction in adiposity and improvement of metabolic disorders are largely unknown...
April 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28402446/adiponectin-and-its-receptors-in-diabetic-kidney-disease-molecular-mechanisms-and-clinical-potential
#10
Dongqing Zha, Xiaoyan Wu, Ping Gao
Diabetic kidney disease (DKD) is a major complication for diabetic patients. Adiponectin is an insulin sensitizer and anti-inflammatory adipokine and is mainly secreted by adipocytes. Two types of adiponectin receptors have been identified, AdipoR1 and AdipoR2. In both type 1 (T1D) and type 2 diabetes (T2D) patients with DKD elevated adiponectin serum levels have been observed and adiponectin serum level is a prognostic factor of end stage renal disease. Renal insufficiency and tubular injury possibly play a contributory role in increases in serum and urinary adiponectin levels in diabetic nephropathy by either increasing biodegradation or elimination of adiponectin in the kidneys, or enhancing production of adiponectin in adipose tissue...
April 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28395010/inflammation-and-metabolic-cardiomyopathy
#11
Kazuhiko Nishida, Kinya Otsu
Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signalling pathways are directly triggered by nutrients. The pro-inflammatory mediators in adipocytes and macrophages infiltrating adipose tissue promote both local and systemic pro-inflammatory status...
March 15, 2017: Cardiovascular 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/28374413/beneficial-effects-of-leptin-treatment-in-a-setting-of-cardiac-dysfunction-induced-by-transverse-aortic-constriction-in-mouse
#13
Nieves Gómez-Hurtado, Alejandro Domínguez-Rodríguez, Philippe Mateo, Maria Fernandez-Velasco, Almudena Val-Blasco, Rafael Aizpún, Jessica Sabourin, Ana Maria Gómez, Jean-Pierre Benitah, Carmen Delgado
KEY POINTS: Leptin, is a 16 kDa pleiotropic peptide, primary secreted by adipocytes, but also produced by other tissues including the heart. Controversy exists regarding the adverse and beneficial effects of Leptin on the heart We analysed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca(2+) ]i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction We find that Leptin activates mechanisms that contribute to cardiac dysfunction in physiological conditions...
April 4, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28361956/role-for-formin-like-1-dependent-acto-myosin-assembly-in-lipid-droplet-dynamics-and-lipid-storage
#14
Simon G Pfisterer, Gergana Gateva, Peter Horvath, Juho Pirhonen, Veijo T Salo, Leena Karhinen, Markku Varjosalo, Samppa J Ryhänen, Pekka Lappalainen, Elina Ikonen
Lipid droplets (LDs) are cellular organelles specialized in triacylglycerol (TG) storage undergoing homotypic clustering and fusion. In non-adipocytic cells with numerous LDs this is balanced by poorly understood droplet dissociation mechanisms. We identify non-muscle myosin IIa (NMIIa/MYH-9) and formin-like 1 (FMNL1) in the LD proteome. NMIIa and actin filaments concentrate around LDs, and form transient foci between dissociating LDs. NMIIa depletion results in decreased LD dissociations, enlarged LDs, decreased hydrolysis and increased storage of TGs...
March 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28359093/diabetes-specific-regulation-of-adipocyte-metabolism-by-the-adipose-tissue-extracellular-matrix
#15
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/28358928/regulation-of-white-and-brown-adipocyte-differentiation-by-rhogap-dlc1
#16
Choon Kiat Sim, Sun-Yee Kim, Reinhard Brunmeir, Qiongyi Zhang, Hongyu Li, Dharmini Dharmasegaran, Carol Leong, Ying Yan Lim, Weiping Han, Feng Xu
Adipose tissues constitute an important component of metabolism, the dysfunction of which can cause obesity and type II diabetes. Here we show that differentiation of white and brown adipocytes requires Deleted in Liver Cancer 1 (DLC1), a Rho GTPase Activating Protein (RhoGAP) previously studied for its function in liver cancer. We identified Dlc1 as a super-enhancer associated gene in both white and brown adipocytes through analyzing the genome-wide binding profiles of PPARγ, the master regulator of adipogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28349253/mangiferin-suppresses-endoplasmic-reticulum-stress-in-perivascular-adipose-tissue-and-prevents-insulin-resistance-in-the-endothelium
#17
Xiaoshan Xu, Yupeng Chen, Junna Song, Fangjie Hou, Xuelian Ma, Baolin Liu, Fang Huang
PURPOSE: Mangiferin is a naturally occurring glucosylxanthone with beneficial effects on glucose and lipid homeostasis. This study investigates the potential therapeutic effect of Mangiferin in perivascular adipose tissue (PVAT) and whether it contributes to regulating insulin action in the endothelium. METHODS: Palmitate challenge evoked ROS-associated endoplasmic reticulum stress (ER stress) and NLRP3 inflammasome activation in PVAT. The conditioned medium from PA-stimulated PVAT was prepared to induce endothelial insulin resistance, and improved endothelium-dependent vasodilation in response to insulin was detected in vitro and in vivo...
March 27, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28330582/adipocyte-accumulation-in-the-bone-marrow-during-obesity-and-aging-impairs-stem-cell-based-hematopoietic-and-bone-regeneration
#18
Thomas H Ambrosi, Antonio Scialdone, Antonia Graja, Sabrina Gohlke, Anne-Marie Jank, Carla Bocian, Lena Woelk, Hua Fan, Darren W Logan, Annette Schürmann, Luis R Saraiva, Tim J Schulz
Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation...
March 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28327709/fish-oil-supplementation-inhibits-endoplasmic-reticulum-stress-and-improves-insulin-resistance-involvement-of-amp-activated-protein-kinase
#19
Wenqi Yang, Xu Chen, Ming Chen, Yanping Li, Qing Li, Xinwei Jiang, Yan Yang, Wenhua Ling
The beneficial effects of fish oil consumption on glucose metabolism have been generally reported. However, the mechanism underlying the fish oil-induced protective effects against insulin resistance remains unclear. Endoplasmic reticulum (ER) stress is recognized as an important contributor to insulin resistance. The aim of this study is to evaluate whether fish oil supplementation reduces ER stress and ameliorates insulin resistance in diet-induced obese mice, and to investigate the molecular mechanism of fish oil-induced benefits on ER stress...
April 19, 2017: Food & Function
https://www.readbyqxmd.com/read/28323914/menopause-is-a-determinant-of-breast-aromatase-expression-and-its-associations-with-bmi-inflammation-and-systemic-markers
#20
Kristy A Brown, Neil M Iyengar, Xi Kathy Zhou, Ayca Gucalp, Kotha Subbaramaiah, Hanhan Wang, Dilip D Giri, Monica Morrow, Domenick J Falcone, Nils K Wendel, Lisle A Winston, Michael Pollak, Anneloor Dierickx, Clifford A Hudis, Andrew J Dannenberg
CONTEXT: Most estrogen-dependent breast cancers occur after menopause despite low levels of circulating estrogens. Breast expression of the estrogen-biosynthetic enzyme, aromatase, is proposed to drive breast cancer development after menopause. However, the effects of menopause on breast aromatase expression are unknown. OBJECTIVE: To determine the effect of menopause on breast aromatase expression in relation to body mass index (BMI), white adipose tissue inflammation (WATi) and systemic markers of metabolic dysfunction...
February 16, 2017: Journal of Clinical Endocrinology and Metabolism
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