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https://www.readbyqxmd.com/read/29035537/discovery-of-a-novel-piperidine-based-inhibitor-of-cholesteryl-ester-transfer-protein-cetp-that-retains-activity-in-hypertriglyceridemic-plasma
#1
Ken Yamada, Margaret Brousseau, Wataru Honma, Akiko Iimura, Hidetomo Imase, Yuki Iwaki, Toshio Kawanami, Daniel LaSala, Guiqing Liang, Hironobu Mitani, Kazuhiko Nonomura, Osamu Ohmori, Meihui Pan, Dean F Rigel, Ichiro Umemura, Kayo Yasoshima, Guoming Zhu, Muneto Mogi
Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead molecule with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency...
October 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29031005/quantitative-high-content-high-throughput-microscopy-analysis-of-lipid-droplets-in-subject-specific-adipogenesis-models
#2
Maxime Bombrun, Hui Gao, Petter Ranefall, Niklas Mejhert, Peter Arner, Carolina Wählby
Neutral lipids packed in lipid droplets (LDs) are essential as a source of fuel for organisms, and specialized storing cells, the adipocytes, provide a buffer for energy variations. Many modern-society-disorders are connected with excess accumulation or deficiency of LDs in adipose tissue. Intracellular LD number and size distribution reflect the tissue conditions, while the associated mechanisms and genes rs are still poorly understood. Large-scale genetic screens using human in vitro differentiated primary adipocytes require cell samples donated from many patients...
October 14, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/29029184/low-plasma-adiponectin-concentrations-predict-increases-in-visceral-adiposity-and-insulin-resistance
#3
Seung Jin Han, Edward J Boyko, Wilfred Y Fujimoto, Steven E Kahn, Donna L Leonetti
Context: Plasma adiponectin concentration has been shown to be inversely associated with body mass index (BMI) and insulin resistance in cross-sectional research. However, it is unclear whether adiponectin predicts future body composition and insulin resistance. Objective: To investigate the potential relationship between adiponectin concentration and future regional body fat distribution and insulin resistance. Design and Setting: Community-based prospective cohort study with 5 years of follow-up...
September 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29027533/factors-associated-with-circulating-concentrations-of-irisin-in-the-general-population-cohort-of-the-abcd-study
#4
S Buscemi, D Corleo, S Vasto, C Buscemi, M F Massenti, D Nuzzo, G Lucisano, A M Barile, G Rosafio, V Maniaci, C Giordano
BACKGROUND: Animal studies have shown that irisin is a myokine secreted following physical exercise, and that it induces the remodeling of white adipose tissue toward brown adipose tissue. Therefore, a protective role of irisin against obesity, diabetes, and other metabolic and cardiovascular conditions has been hypothesized. However, data in humans are contradictory and few data are available concerning the general population. AIMS: We aimed to evaluate the association between serum irisin concentrations and habitual physical activity, as well as other metabolic and cardiovascular factors in a general population in a Mediterranean area...
October 13, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29024558/overweight-obesity-and-adiposity-in-survivors-of-childhood-brain-tumours-a-systematic-review-and-meta-analysis
#5
REVIEW
K-W Wang, A Fleming, D L Johnston, S M Zelcer, S R Rassekh, S Ladhani, A Socha, J Shinuda, S Jaber, S Burrow, S K Singh, L Banfield, R J de Souza, L Thabane, M C Samaan
Survivors of childhood brain tumours (SCBT) have increased cardiometabolic risks, but the determinants of these risks are unclear. This systematic review aims to compare the prevalence of overweight and obesity as well as adiposity measures between SCBT and non-cancer controls. The PubMed, EMBASE, MEDLINE, CINAHL and the Cochrane Library databases were searched. The primary outcomes were the prevalence of overweight and obesity based on body mass index. The secondary outcomes were adiposity measures including percent fat mass, waist-to-hip and waist-to-height ratios...
October 11, 2017: Clinical Obesity
https://www.readbyqxmd.com/read/29023058/morphometric-characteristics-of-asian-catfish-hemibagrus-wyckii-bleeker-1858-bagridae-from-the-riau-province-of-indonesia
#6
Netti Aryani, Saberina Hasibuan, Ainul Mardiah, Hafrijal Syandri
BACKGROUND AND OBJECTIVE: Asian Catfish (Hemibagrus wyckii) is an important fish having both food and a high price in the market. These species are categorized as a carnivorous freshwater finfish native in Indonesia and is vulnerable to endangered status. This study was carried out to identify the morphometric characteristics of Hemibagrus wyckii (H. wyckii) from the Koto Panjang Reservoir, Kampar Kanan and Kampar Kiri rivers. MATERIALS AND METHODS: Twenty-five fish were collected from each sampling site...
2017: Pakistan Journal of Biological Sciences: PJBS
https://www.readbyqxmd.com/read/29021094/socio-demographic-lifestyle-and-dietary-determinants-of-essential-and-possibly-essential-trace-element-levels-in-adipose-tissue-from-an-adult-cohort
#7
Celia Rodríguez-Pérez, Petra Vrhovnik, Beatriz González-Alzaga, Mariana F Fernández, Piedad Martin-Olmedo, Nicolás Olea, Željka Fiket, Goran Kniewald, Juan P Arrebola
There is increasing evidence linking levels of trace elements (TEs) in adipose tissue with certain chronic conditions (e.g., diabetes or obesity). The objectives of this study were to assess concentrations of a selection of nine essential and possibly-essential TEs in adipose tissue samples from an adult cohort and to explore their socio-demographic, dietary, and lifestyle determinants. Adipose tissue samples were intraoperatively collected from 226 volunteers recruited in two public hospitals from Granada province...
October 8, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29019279/leucine-and-resistance-training-improve-hyperglycemia-white-adipose-tissue-loss-and-inflammatory-parameters-in-an-experimental-model-of-type-1-diabetes
#8
Henrique Quintas Teixeira Ribeiro, Audrey Yule Coqueiro, Vanessa Batista de Sousa Lima, Carlos Eduardo Carvalho Martins, Julio Tirapegui
BACKGROUND: Loss of white adipose tissue (WAT), associated with type 1 diabetes (DM1), contributes to increased chronic systemic inflammation. AIM: The aim of this study was to investigate the effects of leucine supplementation and resistance training (RT) in attenuating WAT loss and improving inflammatory parameters and glucose metabolism in DM1 rats. METHODS: Thirty-two male Wistar rats were distributed into four groups: DA (sedentary and supplemented with non-essential amino acids (NEAA)), DL (sedentary and supplemented with leucine), DTA (submitted to RT and supplemented with NEAA) and DTL (submitted to RT and supplemented with leucine)...
January 1, 2017: Nutrition and Health
https://www.readbyqxmd.com/read/28994225/scaffold-composition-determines-the-angiogenic-outcome-of-cell-based-vascular-endothelial-growth-factor-expression-by-modulating-its-microenvironmental-distribution
#9
Emanuele Gaudiello, Ludovic Melly, Giulia Cerino, Stefano Boccardo, Sasan Jalili-Firoozinezhad, Lifen Xu, Friedrich Eckstein, Ivan Martin, Beat A Kaufmann, Andrea Banfi, Anna Marsano
Delivery of genetically modified cells overexpressing Vascular Endothelial Growth Factor (VEGF) is a promising approach to induce therapeutic angiogenesis in ischemic tissues. The effect of the protein is strictly modulated by its interaction with the components of the extracellular matrix. Its therapeutic potential depends on a sustained but controlled release at the microenvironmental level in order to avoid the formation of abnormal blood vessels. In this study, it is hypothesized that the composition of the scaffold plays a key role in modulating the binding, hence the therapeutic effect, of the VEGF released by 3D-cell constructs...
October 10, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28986436/normal-human-adipose-tissue-functions-and-differentiation-in-patients-with-biallelic-lpin1-inactivating-mutations
#10
Michele Pelosi, Eric Testet, Soazig Le Lay, Isabelle Dugail, Xiaoyun Tang, Guillaume Mabilleau, Yamina Hamel, Marine Madrange, Thomas Blanc, Thierry Odent, Todd P W McMullen, Marco Alfò, David N Brindley, Pascale de Lonlay
Lipin-1 is a Mg2+-dependent phosphatidic acid phosphatase (PAP) that in mice is necessary for normal glycerolipid biosynthesis, controlling adipocytes metabolism and adipogenic differentiation. Mice carrying inactivating mutations in the Lpin1 gene display the characteristic features of human familial lipodystrophy. Very little is known on the roles of lipin-1 in human adipocyte physiology. Apparently fat distribution and weight is normal in humans carrying LPIN1 inactivating mutations, but a detailed analysis of adipose tissue appearance and functions in these patients has not been available so far...
October 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28983743/pet-imaging-of-human-brown-adipose-tissue-with-the-tspo-tracer-11-c-pbr28
#11
Chongzhao Ran, Daniel S Albrecht, Miriam A Bredella, Jing Yang, Jian Yang, Steven H Liang, Aaron M Cypess, Marco L Loggia, Nazem Atassi, Anna Moore
PURPOSE: Brown adipose tissue (BAT) in adult humans has been recently rediscovered and intensively investigated as a new potential therapeutic target for obesity and type 2 diabetes (T2D). However, reliable assessment of BAT mass in vivo represents a considerable challenge. The purpose of this investigation is to demonstrate for the first time that human BAT depots can be imaged with a translocator protein (TSPO)-specific positron emission tomography (PET) tracer [(11)C]PBR28 under thermoneutral conditions...
October 5, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28983157/obesity-and-associated-cardiometabolic-risk-among-women-from-tripura-a-northeastern-state-of-india
#12
Purnajita Sen, Sandeep Das, Samrat Hore, Surajit Bhattacharjee, Dipayan Choudhuri
INTRODUCTION: Cardiometabolic health status of women is a serious public health concern. Markers of body fat content and their distribution are important indicators of cardiometabolic health risk in participants. In addition, socio-demographic status plays a determinant role. The aim of the study was to evaluate the influence of adiposity markers and socio-demographic determinants on various cardiovascular and metabolic risk factors in Indian women. MATERIALS AND METHODS: The study was conducted on 388 women (age 25-65 years) from Tripura, a Northeastern state of India...
July 2017: Journal of Mid-life Health
https://www.readbyqxmd.com/read/28977588/hexarelin-a-growth-hormone-secretagogue-improves-lipid-metabolic-aberrations-in-nonobese-insulin-resistant-male-mkr-mice
#13
Rasha Mosa, Lili Huang, Yeda Wu, Chungyan Fung, Oshini Mallawakankanamalage, Derek LeRoith, Chen Chen
Despite the occurrence of dyslipidemia and its contribution to the development of insulin resistance in obese subjects, a growing number of studies have described abnormal lipid profiles among leaner persons. For example, individuals with an abnormal paucity or distribution of fat (lipodystrophy) develop severe insulin resistance, dyslipidemia, and hepatic steatosis. Deranged adipocyte metabolism and differentiation contribute to ectopic fat deposition and consequent development of insulin resistance. Growth hormone (GH) therapy has been shown to correct body composition abnormalities in some lipodystrophy patients...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28975197/association-of-multiorgan-computed-tomographic-phenomap-with-adverse-cardiovascular-health-outcomes-the-framingham-heart-study
#14
Ravi V Shah, Ashish S Yeri, Venkatesh L Murthy, Joe M Massaro, Ralph D'Agostino, Jane E Freedman, Michelle T Long, Caroline S Fox, Saumya Das, Emelia J Benjamin, Ramachandran S Vasan, Christopher J O'Donnell, Udo Hoffmann
Importance: Increased ability to quantify anatomical phenotypes across multiple organs provides the opportunity to assess their cumulative ability to identify individuals at greatest susceptibility for adverse outcomes. Objective: To apply unsupervised machine learning to define the distribution and prognostic importance of computed tomography-based multiorgan phenotypes associated with adverse health outcomes. Design, Setting, and Participants: This asymptomatic community-based cohort study included 2924 Framingham Heart Study participants between July 2002 and April 2005 undergoing computed tomographic imaging of the chest and abdomen...
September 20, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28974138/cardiovascular-risk-of-adipokines-a-review
#15
Frédéric Dutheil, Brett Ashley Gordon, Geraldine Naughton, Edward Crendal, Daniel Courteix, Elodie Chaplais, David Thivel, Gérard Lac, Amanda Clare Benson
Over the last two decades, the understanding of adipose tissue has undergone radical change. The perception has evolved from an inert energy storage tissue to that of an active endocrine organ. Adipose tissue releases a cluster of active molecules named adipokines. The severity of obesity-related diseases does not necessarily correlate with the extent of body fat accumulation but is closely related to body fat distribution, particularly to visceral localization. There is a distinction between the metabolic function of central obesity (visceral abdominal) and peripheral obesity (subcutaneous) in the production of adipokines...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28959056/irs1-dna-promoter-methylation-and-expression-in-human-adipose-tissue-are-related-to-fat-distribution-and-metabolic-traits
#16
Kerstin Rohde, Matthias Klös, Lydia Hopp, Xuanshi Liu, Maria Keller, Michael Stumvoll, Arne Dietrich, Michael R Schön, Daniel Gärtner, Tobias Lohmann, Miriam Dreßler, Peter Kovacs, Hans Binder, Matthias Blüher, Yvonne Böttcher
The SNP variant rs2943650 near IRS1 gene locus was previously associated with decreased body fat and IRS1 gene expression as well as an adverse metabolic profile in humans. Here, we hypothesize that these effects may be mediated by an interplay with epigenetic alterations. We measured IRS1 promoter DNA methylation and mRNA expression in paired human subcutaneous and omental visceral adipose tissue samples (SAT and OVAT) from 146 and 41 individuals, respectively. Genotyping of rs2943650 was performed in all individuals (N = 146)...
September 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28957363/body-fat-distribution-in-particular-visceral-fat-is-associated-with-cardiometabolic-risk-factors-in-obese-women
#17
Theodora W Elffers, Renée de Mutsert, Hildo J Lamb, Albert de Roos, Ko Willems van Dijk, Frits R Rosendaal, J Wouter Jukema, Stella Trompet
BACKGROUND: Body fat distribution is, next to overall obesity, an important risk factor for cardiometabolic outcomes in the general population. In particular, visceral adipose tissue (VAT) is strongly associated with cardiometabolic risk factors. Since it is unclear whether body fat distribution is also important in men and women with obesity we investigated the associations between measures of body fat distribution and cardiometabolic risk factors in men and women with obesity. METHODS: In this cross-sectional analysis of obese men and women (BMI≥30 kg/m2) included in the Netherlands Epidemiology of Obesity Study, waist:hip ratio(WHR), waist circumference, and MRI-based abdominal subcutaneous adipose tissue (aSAT) and VAT were determined...
2017: PloS One
https://www.readbyqxmd.com/read/28952607/vitamin-k-induced-effects-on-body-fat-and-weight-results-from-a-3-year-vitamin-k2-intervention-study
#18
M H J Knapen, K M Jardon, C Vermeer
BACKGROUND/OBJECTIVES: Vitamin K status has been linked to fat and glucose metabolism by several authors, but whether high vitamin K intake influences body weight or composition has remained unclear. Here we tested the hypothesis that increased vitamin K intake decreases body fat or fat distribution. SUBJECTS/METHODS: In a randomized placebo-controlled human intervention trial, 214 postmenopausal women, 55-65 years of age, received either 180 mcg/day of vitamin K2 (menaquinone-7, MK-7) or placebo for 3 years...
September 27, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28951790/vagotomy-reduces-insulin-clearance-in-obese-mice-programmed-by-low-protein-diet-in-the-adolescence
#19
Camila Lubaczeuski, Luciana Mateus Gonçalves, Jean Franciesco Vettorazzi, Mirian Ayumi Kurauti, Junia Carolina Santos-Silva, Maria Lúcia Bonfleur, Antonio Carlos Boschero, José Maria Costa-Júnior, Everardo Magalhães Carneiro
The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28950723/transplantation-of-hgf-modified-dental-pulp-stem-cells-prevents-bone-loss-in-the-early-phase-of-ovariectomy-induced-osteoporosis
#20
Fanxuan Kong, Xuefeng Shi, FengJun Xiao, Yuefeng Yang, Xiaoyan Zhang, Li-Sheng Wang, Chu-Tse Wu, Hua Wang
Investigations based on mesenchymal stem cells (MSCs) for osteoporosis have been obtained intensive attention recently. MSCs can derive from various tissues, such as bone marrow, adipose, umbilical cord, placenta, dental pulp, etc. Among them, dental pulp derived MSCs (DPSCs) and hepatocyte growth factor (HGF)-modified DPSCs (DPSCs-HGF) highly expressed osteogenic related genes and have stronger osteogenic differentiation capacities. DPSCs have more benefits in treating osteoporosis. The purpose of this study is to investigate the roles of HGF gene modified DPSCs in bone regeneration using a mouse model of ovariectomy (OVX)-induced bone loss...
September 26, 2017: Human Gene Therapy
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