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https://www.readbyqxmd.com/read/28646531/morin-a-novel-lxr%C3%AE-%C3%AE-dual-antagonist-has-potent-therapeutic-efficacy-for-nonalcoholic-fatty-liver-diseases
#1
Ming Gu, Yu Zhang, Chuhe Liu, Dongshan Wang, Li Feng, Shengjie Fan, Baican Yang, Qingchun Tong, Guang Ji, Cheng Huang
BACKGROUND AND PURPOSE: Morin is a natural occurring flavonoid in many dietary plants and has a wide range of beneficial effects on metabolism; however, the mechanism underlying its action remains elusive. EXPERIMENTAL APPROACH: Reporter assay and the Time-Resolved Fluorescence Resonance Energy Transfer assay were used to identify morin as a dual antagonist of LXRα and LXRβ. High fat-diet mixed with morin (100 mg/100 g diet) was administrated to high-fat diet-induced obese or LXRβ(-/-) mice combining with Western blot and RT-PCR analysis to evaluate the pharmacological effect and mechanism of morin treatment...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646121/at1-receptor-blockade-attenuates-outward-aortic-remodeling-associated-with-diet-induced-obesity-in-mice
#2
Friedrich Krueger, Kai Kappert, Anna Foryst-Ludwig, Frederike Kramer, Markus Clemenz, Aleksandra Grzesiak, Manuela Sommerfeld, Jan Paul Bernhard Frese, Andreas Greiner, Ulrich Kintscher, Thomas Unger, Elena Kaschina
The renin-angiotensin-system and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are yet not understood. We investigated the effect of the angiotensin AT1-receptor antagonist telmisartan on aortic outward remodeling in a diet-induced obesity-model in mice. C57/Black6J mice were fed with either a low-fat diet (LFD), or a high-fat diet (HFD) for 14 weeks. One group of HFD-mice was additionally exposed to telmisartan (3mg/kg/d) for the last 4 weeks. HFD led to aortic outward remodeling, characterized by increased proteolysis, along with structural changes, such as fragmentation of elastic fibres, and decreased elastin content...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28635626/adiponectin-a-therapeutic-target-for-obesity-diabetes-and-endothelial-dysfunction
#3
REVIEW
Arunkumar E Achari, Sushil K Jain
Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can also produce this adipocytokine. Adiponectin effects are mediated by adiponectin receptors, which occur as two isoforms (AdipoR1 and AdipoR2). Adiponectin has direct actions in liver, skeletal muscle, and the vasculature...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28628672/low-dose-exposure-to-bisphenols-a-f-and-s-of-human-primary-adipocyte-impacts-coding-and-non-coding-rna-profiles
#4
Marie Verbanck, Mickaël Canouil, Audrey Leloire, Véronique Dhennin, Xavier Coumoul, Loïc Yengo, Philippe Froguel, Odile Poulain-Godefroy
Bisphenol A (BPA) exposure has been suspected to be associated with deleterious effects on health including obesity and metabolically-linked diseases. Although bisphenols F (BPF) and S (BPS) are BPA structural analogs commonly used in many marketed products as a replacement for BPA, only sparse toxicological data are available yet. Our objective was to comprehensively characterize bisphenols gene targets in a human primary adipocyte model, in order to determine whether they may induce cellular dysfunction, using chronic exposure at two concentrations: a "low-dose" similar to the dose usually encountered in human biological fluids and a higher dose...
2017: PloS One
https://www.readbyqxmd.com/read/28627722/pterostilbene-inhibits-lipogenic-activity-similar-to-resveratrol-or-caffeine-but-differently-modulates-lipolysis-in-adipocytes
#5
Saioa Gomez-Zorita, Chloé Belles, Anaïs Briot, Alfredo Fernández-Quintela, Maria P Portillo, Christian Carpéné
The anti-obesity effects of resveratrol shown in rodents are not transposed into an efficient therapy of human obesity. Consequently, the search for molecules mimicking or surpassing resveratrol actions is ongoing. The natural phenolic compound pterostilbene exhibits beneficial health effects and has the capacity to limit fat mass in animal models. In this study, we tested whether pterostilbene modulates triacylglycerol accumulation/breakdown. Prolonged exposure to pterostilbene or resveratrol inhibited adipocyte differentiation in 3T3-F442A preadipocytes...
June 19, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28627656/adipokines-and-free-fatty-acids-regulate-insulin-sensitivity-by-increasing-microrna-21-expression-in-human-mature-adipocytes
#6
Nannan Zhang, Naijian Zhang, Leilei Song, Hui Xie, Chao Zhao, Sujuan Li, Wenxi Zhao, Yaping Zhao, Chunlin Gao, Guangfeng Xu
Obesity is a global public health concern and may lead to a variety of complications. Previous studies have indicated that adipokines and energy‑source materials contribute to obesity and obesity‑associated insulin resistance. MicroRNAs (miRs) are endogenous 20‑ to 25‑nucleotide non‑coding RNAs associated with fat metabolism. It has been indicated that miR‑21 is associated with adipogenesis and metabolic syndrome. In the present study, the expression of miR‑21 in human mature adipocytes was analyzed using reverse transcription quantitative‑polymerase chain reaction following treatment with adipokines, including tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, leptin, resistin and energy source materials, including free fatty acids (FFAs) and glucose...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626215/genetic-variation-in-the-obesity-gene-fto-is-not-associated-with-decreased-fat-oxidation-the-neo-study
#7
L L Blauw, R Noordam, S Trompet, J F P Berbée, F R Rosendaal, D van Heemst, K W van Dijk, D O Mook-Kanamori, R de Mutsert, P C N Rensen
BACKGROUND: The FTO gene harbours the strongest common genetic variant associated with obesity. Recently, rs1421085-T to -C substitution mapped in FTO was shown to induce a developmental shift of human adipocytes from an energy-combusting beige to an energy-storing white phenotype in vitro. As browning of adipocytes selectively enhances fat oxidation (FatOx), we hypothesized that rs1421085-C in FTO is associated with deceased FatOx compared with carbohydrate oxidation (CarbOx) and an increased respiratory quotient (RQ)...
June 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28626214/growth-hormone-releasing-hormone-is-produced-by-adipocytes-and-regulates-lipolysis-through-growth-hormone-receptor
#8
F Rodríguez-Pacheco, C Gutierrez-Repiso, S García-Serrano, A Ho-Plagaro, J M Gómez-Zumaquero, S Valdes, M Gonzalo, J Rivas-Becerra, C Montiel-Casado, G Rojo-Martínez, E García-Escobar, E Garcia-Fuentes
BACKGROUND: Growth hormone-releasing hormone (GHRH) plays a crucial role in growth hormone (GH) secretion, but little is known about its production by adipocytes and its involvement in adipocyte metabolism. OBJECTIVES: To determine if GHRH and its receptor (GHRH-R) are present in human adipocytes and to study their levels in obesity. Also, to analize the effects of GHRH on human adipocyte differentiation and lipolysis. METHODS: GHRH/GHRH-R and GH/GH-R mRNA expression levels were analyzed in human mature adipocytes from non-obese and morbidly obese subjects...
June 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28619625/hmgb1-an-innate-alarmin-plays-a-critical-role-in-chronic-inflammation-of-adipose-tissue-in-obesity
#9
REVIEW
Jing Zhang, Lei Zhang, Shu Zhang, Qilin Yu, Xiong Fei, Kun Huang, Cong-Yi Wang, Ping Yang
Obesity has emerged as an imminent global public health concern over the past several decades. It has now become evident that obesity is characterized by the persistent and low-grade inflammation in the adipose tissue, and serves as an independent risk factor for many metabolic disorders such as diabetes and cardiovascular disease. Particularly, adipocytes originated from obese mice and humans likely predominate necrosis upon stressful insults, leading to passive release of cellular contents including the high mobility group box 1 (HMGB1) into the extracellular milieu...
June 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28614778/the-human-immunodeficiency-virus-hiv1-protease-inhibitor-sanquinavir-activates-autophagy-and-removes-lipids-deposited-in-lipid-droplets
#10
A Polus, M Bociaga-Jasik, U Czech, J Goralska, U Cialowicz, M Chojnacka, M Polus, K Jurowski, A Dembinska-Kiec
Reduction in mortality and increased average life span of the human immunodeficiency virus (HIV)-infected patients treated with antiretroviral therapy (ART) are associated with the risk of unwanted effects, such as insulin resistance and dyslipidemia with cardiovascular complications. Antiretroviral therapy may also be associated with lipodystrophy characterized as peripheral lipoatrophy with central fat accumulation. Understanding the molecular mechanisms of lipodystrophy caused by ART is important for therapeutic strategy and the prediction of side-effects...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28613919/hypercapnia-accelerates-adipogenesis-a-novel-role-of-high-co2-in-exacerbating-obesity
#11
Ryota Kikuchi, Takao Tsuji, Osamu Watanabe, Kazuhiro Yamaguchi, Kinya Furukawa, Hiroyuki Nakamura, Kazutetsu Aoshiba
Obesity is a major risk factor for the development of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS), which manifest as intermittent hypercapnia and sustained plus intermittent hypercapnia, respectively. In this study, we investigated whether CO2 affects adipocyte differentiation (adipogenesis) and maturation (hypertrophy). Human visceral or subcutaneous preadipocytes were grown to confluence and then induced to differentiate to adipocytes under hypocapnia, normocapnia, and hypercapnia with or without hypoxia...
June 14, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28612196/cell-source-differentiation-functional-stimulation-and-potential-application-of-human-thermogenic-adipocytes-in-vitro
#12
REVIEW
Dinh-Toi Chu, Yang Tao, Le Hoang Son, Duc-Hau Le
Recent investigations have showed that the functional thermogenic adipocytes are present in both infants and adult humans. Accumulating evidence suggests that the coexistence of classical and inducible brown (brite) adipocytes in humans at adulthood and these adipocytes function to generate heat from energy resulting in reducing body fat and improving glucose metabolism. Human thermogenic adipocytes can be differentiated in vitro from stem cells, cell lines, or adipose stromal vascular fraction. Pre-activated human brite adipocytes in vitro can maintain their thermogenic function in normal or obese immunodeficient mice; therefore, they improve glucose homeostasis and reduce fat mass in obese animals...
June 14, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28606124/remodeling-adipose-tissue-through-in-silico-modulation-of-fat-storage-for-the-prevention-of-type-2-diabetes
#13
Thierry Chénard, Frédéric Guénard, Marie-Claude Vohl, André Carpentier, André Tchernof, Rafael J Najmanovich
BACKGROUND: Type 2 diabetes is one of the leading non-infectious diseases worldwide and closely relates to excess adipose tissue accumulation as seen in obesity. Specifically, hypertrophic expansion of adipose tissues is related to increased cardiometabolic risk leading to type 2 diabetes. Studying mechanisms underlying adipocyte hypertrophy could lead to the identification of potential targets for the treatment of these conditions. RESULTS: We present iTC1390adip, a highly curated metabolic network of the human adipocyte presenting various improvements over the previously published iAdipocytes1809...
June 12, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28595552/pigment-epithelium-derived-factor-a-novel-therapeutic-target-for-cardiometabolic-diseases-and-related-complications
#14
Sho-Ichi Yamagishi, Takanori Matsui
Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors, serpins. It was first identified as a neuronal differentiating factor secreted by human retinal pigment epithelial cells, and then found to be the most potent inhibitor of pathological angiogenesis in mammalian eyes. Recently, PEDF has been shown not only to suppress oxidative stress and inflammatory reactions in vascular wall cells, T cells and macrophages, and adipocytes, but also to exert anti-thrombotic and anti-fibrotic properties, thereby protecting against the development and progression of various cardiometabolic diseases and related complications...
June 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28593918/beyond-obesity-thermogenic-adipocytes-and-cardiometabolic-health
#15
Peter Aldiss, Neele Dellschaft, Harold Sacks, Helen Budge, Michael E Symonds
The global prevalence of obesity and related cardiometabolic disease continues to increase through the 21st century. Whilst multi-factorial, obesity is ultimately caused by chronic caloric excess. However, despite numerous interventions focussing on reducing caloric intake these either fail or only elicit short-term changes in body mass. There is now a focus on increasing energy expenditure instead which has stemmed from the recent 're-discovery' of cold-activated brown adipose tissue (BAT) in adult humans and inducible 'beige' adipocytes...
May 26, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28592814/impairment-of-the-activin-a-autocrine-loop-by-lopinavir-reduces-self-renewal-of-distinct-human-adipose-progenitors
#16
Christophe Ravaud, Martin Paré, Stéphane Azoulay, Christian Dani, Annie Ladoux
Maintenance of the adipose tissue requires a proper balance between self-renewal and differentiation of adipose progenitors (AP). Any deregulation leads either to fat overexpansion and obesity or fat loss and consequent lipodystrophies. Depending on the fat pad location, APs and adipocytes are heterogeneous. However, information on the pharmacological sensitivity of distinct APs to drugs known to alter the function of adipose tissue, especially HIV protease inhibitors (PIs) is scant. Here we show that PIs decreased proliferation and clonal expansion of APs, modifying their self-renewal potential...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592801/immune-cell-derived-cytokines-contribute-to-obesity-related-inflammation-fibrogenesis-and-metabolic-deregulation-in-human-adipose-tissue
#17
Charles Caër, Christine Rouault, Tiphaine Le Roy, Christine Poitou, Judith Aron-Wisnewsky, Adriana Torcivia, Jean-Christophe Bichet, Karine Clément, Michèle Guerre-Millo, Sébastien André
Adipose tissue contains a variety of immune cells, which vary in abundance and phenotype with obesity. The contribution of immune cell-derived factors to inflammatory, fibrotic and metabolic alterations in adipose tissue is not well established in human obesity. Human primary adipose tissue cells, including pre-adipocytes, endothelial cells and mature adipocytes, were used to investigate deregulation of cell- and pathway-specific gene profiles. Among factors known to alter adipose tissue biology, we focus on inflammatory (IL-1β and IL-17) and pro-fibrotic (TGF-β1) factors...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592656/hypothalamic-circuits-regulating-appetite-and-energy-homeostasis-pathways-to-obesity
#18
REVIEW
Katharina Timper, Jens C Brüning
The 'obesity epidemic' represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure...
June 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28585197/human-protein-kinases-and-obesity
#19
Atilla Engin
The action of protein kinases and protein phosphatases is essential for multiple physiological responses. Each protein kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by association with other proteins. Protein kinases are classified by the target amino acid in their substrates. Some protein kinases can phosphorylate both serine/threonine, as well as tyrosine residues. This group of kinases has been known as dual specificity kinases. Unlike the dual specificity kinases, a heterogeneous group of protein phosphatases are known as dual-specificity phosphatases...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28576408/browning-effects-of-epicatechin-on-adipocytes-and-white-adipose-tissue
#20
Claudia Elena Varela, Alonso Rodriguez, Mirza Romero-Valdovinos, Patricia Mendoza-Lorenzo, Christina Mansour, Guillermo Ceballos, Francisco Villarreal, Israel Ramirez-Sanchez
In this study, we demonstrate that (-)-epicatechin (Epi), a cacao flavanol, induces the browning of fat by promoting mitochondrial biogenesis, enhancing indicators of mitochondrial structure and function, increasing fatty acid metabolism and upregulating the expression of brown adipose tissue-specific proteins in a high-fat diet mouse model of obesity and in cultured human adipocytes. Epi treatment significantly improved mitochondrial function, as measured by citrate synthase activity, and also reduced protein acetylation of total and specific regulators in both adipose tissue and human adipocytes...
May 30, 2017: European Journal of Pharmacology
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