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Esther Alhelí Hernández-Tobías, Luisa Torres-Sánchez, Gino Noris, Carla Santana, María Reyna Samano, José Arellano-Galindo, María de la Luz Arenas-Sordo, Daniel Brooks, Ana Lilia Rodríguez-Ventura, Marco Antonio Meraz-Ríos, Rocío Gómez
OBJECTIVE: We studied multi-loci variants to identify the contribution of six candidate genes (ADIPOQ, CDH13, LYPLAL1, MC4R, PPARG and PGC1A) in the development of obesity and overweight. DESIGN: We genotyped 404 chromosomes with eleven SNPs in Mexican female adolescents, who were subdivided into two groups (obesity-overweight and normal-weight) using the World Health Organization parameters. Genomic (800 chromosomes) and ancestral (208 chromosomes) controls were included to reduce the population bias...
October 20, 2016: Ethnicity & Disease
Yvonne N Flores, Rafael Velázquez-Cruz, Paula Ramírez, Manuel Bañuelos, Zuo-Feng Zhang, Hal F Yee, Shen-Chih Chang, Samuel Canizales-Quinteros, Manuel Quiterio, Guillermo Cabrera-Alvarez, Nelly Patiño, Jorge Salmerón
There is scarce information about the link between specific single-nucleotide polymorphisms (SNPs) and risk of liver disease among Latinos, despite the disproportionate burden of disease among this population. Our aim was to investigate nine SNPs in or near the following genes: PNPLA3, LYPLAL1, PPP1R3B, GCKR, NCAN, IRS1, PPARG, and ADIPOR2 and examine their association with persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels in Mexican adults. Data and samples were collected from 741 participants in the Mexican Health Worker Cohort Study, in Cuernavaca, Mexico...
October 17, 2016: Molecular Biology Reports
Amit R Majithia, Ben Tsuda, Maura Agostini, Keerthana Gnanapradeepan, Robert Rice, Gina Peloso, Kashyap A Patel, Xiaolan Zhang, Marjoleine F Broekema, Nick Patterson, Marc Duby, Ted Sharpe, Eric Kalkhoven, Evan D Rosen, Inês Barroso, Sian Ellard, Sekar Kathiresan, Stephen O'Rahilly, Krishna Chatterjee, Jose C Florez, Tarjei Mikkelsen, David B Savage, David Altshuler
Clinical exome sequencing routinely identifies missense variants in disease-related genes, but functional characterization is rarely undertaken, leading to diagnostic uncertainty. For example, mutations in PPARG cause Mendelian lipodystrophy and increase risk of type 2 diabetes (T2D). Although approximately 1 in 500 people harbor missense variants in PPARG, most are of unknown consequence. To prospectively characterize PPARγ variants, we used highly parallel oligonucleotide synthesis to construct a library encoding all 9,595 possible single-amino acid substitutions...
October 17, 2016: Nature Genetics
Tessa D Nauta, Marloes van den Broek, Sue Gibbs, Tineke C T M van der Pouw-Kraan, Cees B Oudejans, Victor W M van Hinsbergh, Pieter Koolwijk
During prolonged hypoxic conditions, endothelial cells change their gene expression to adjust to the low oxygen environment. This process is mainly regulated by the hypoxia-inducible factors, HIF-1α and HIF-2α. Although endothelial cells do not form sprouts during prolonged hypoxic culturing, silencing of HIF-2α partially restores sprout formation. The present study identifies novel HIF-2α-target genes that may regulate endothelial sprouting during prolonged hypoxia. The gene expression profile of primary human microvascular endothelial cells (hMVECs) that were cultured at 20 % oxygen was compared to hMVECs that were cultured at 1 % oxygen for 14 days by using genome-wide RNA-sequencing...
October 3, 2016: Angiogenesis
Jordan Kardos, Shengjie Chai, Lisle E Mose, Sara R Selitsky, Bhavani Krishnan, Ryoichi Saito, Michael D Iglesia, Matthew I Milowsky, Joel S Parker, William Y Kim, Benjamin G Vincent
We report the discovery of a claudin-low molecular subtype of high-grade bladder cancer that shares characteristics with the homonymous subtype of breast cancer. Claudin-low bladder tumors were enriched for multiple genetic features including increased rates of RB1, EP300, and NCOR1 mutations; increased frequency of EGFR amplification; decreased rates of FGFR3, ELF3, and KDM6A mutations; and decreased frequency of PPARG amplification. While claudin-low tumors showed the highest expression of immune gene signatures, they also demonstrated gene expression patterns consistent with those observed in active immunosuppression...
March 17, 2016: JCI Insight
Mei-Hua Bao, Huai-Qing Luo, Li-Hua Chen, Liang Tang, Kui-Fen Ma, Ju Xiang, Li-Ping Dong, Jie Zeng, Guang-Yi Li, Jian-Ming Li
Atherosclerosis is a chronic multifactorial inflammatory disease with high prevalence worldwide, and has become the leading cause of death. The present study was designed to investigate the impact of high-fat diet on ApoE(-/-) mice exhibiting atherosclerosis by detecting the genome-wide expression profile of lncRNAs and mRNAs. A total of 354 differentially expressed lncRNAs were identified (≥2.0 folds). Simultaneously, 357 differentially expressed mRNAs from the same chip were found. The expression differences of lncRNAs and mRNAs were consistent in both qPCR and microarray detection...
October 4, 2016: Scientific Reports
Tingting Kang, Disha Peng, Guowei Bu, Hao Gu, Feng Zhang, Ruirui Zhang, Ying Zhou, Yuanzhu Xiong, Minggang Lei
FAM3A (family with sequence similarity 3, member A) is regulated by PPARG and participates in the metabolism of lipid in liver. However, the transcriptional regulation analysis of FAM3A is very little and biological function of FAM3A still unclear. In this study, the core promoter region and transcription factor binding sites of FAM3A gene were identified and characterized using dual luciferase report experiments and electrophoretic mobility shift assays (EMSA). The promoter activity of FAM3A was dramatically decreased after the mutation of C/EBPβ binding sites, suggesting that C/EBPβ is a transcriptional activator of FAM3A...
September 26, 2016: Gene
Briana Foley, Daniel Doheny, Michael Black, Salil N Pendse, Barbara Wetmore, Rebecca Clewell, Melvin E Andersen, Chad Deisenroth
The developmental origins of obesity hypothesis posits a multifaceted contribution of factors to the fetal origins of obesity and metabolic disease. Adipocyte hyperplasia in gestation and early childhood may result in predisposition for obesity later in life. Rodent in vitro and in vivo studies indicate that some chemicals may directly affect adipose progenitor cell differentiation, but the human relevance of these findings is unclear. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARG) is the master regulator of adipogenesis...
September 23, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Aurèle Besse-Patin, Mélissa Léveillé, Daniel Oropeza, Bich N Nguyen, Annick Prat, Jennifer L Estall
BACKGROUND & AIMS: Inefficient fatty acid oxidation in mitochondria and increased oxidative damage are features of non-alcoholic fatty liver disease (NAFLD). In rodent models and patients with NAFLD, hepatic expression of PPARG coactivator 1 alpha (PPARGC1A or PGC1A) is inversely correlated with liver fat and disease severity. A common polymorphism in this gene (rs8192678, encoding Gly482Ser) has been associated with NAFLD. We investigated whether reduced expression of PGC1A contributes to development of NAFLD using mouse models, primary hepatocytes and human cell lines...
September 19, 2016: Gastroenterology
Jessica I Grill, Jens Neumann, Andreas Herbst, Andrea Ofner, Felix Hiltwein, Maximilian K Marschall, Heike Zierahn, Eckhard Wolf, Marlon R Schneider, Frank T Kolligs
To investigate the role of DRO1 in obesity and adipogenesis in vivo, we generated a constitutive Dro1 knockout mouse model and analyzed the effect of DRO1 loss on body growth under standard and high fat diet feeding conditions. Loss of DRO1 resulted in a significant increase in body weight which was accompanied by a substantial expansion of white adipose tissue depots. The obese phenotype could be further enhanced by a high fat dietary challenge which also resulted in impaired glucose metabolism and the development of hepatosteatosis in Dro1 knockout mice...
September 16, 2016: Molecular and Cellular Endocrinology
Laura G Goetz, Ramanaiah Mamillapalli, Hugh S Taylor
The gynecological disease endometriosis is characterized by the deposition and proliferation of the endometrial cells outside the uterus and is linked to low body mass index (BMI) clinically. Gene expression in the liver of these women has not been reported. We hypothesized that endometriosis may impact hepatic gene expression to promote a low BMI. To determine the effect of endometriosis on liver gene expression, we induced endometriosis in female mice by suturing donor mouse endometrium into the peritoneal cavity and measuring the weights of these mice...
September 14, 2016: Biology of Reproduction
Christa Broholm, Anders H Olsson, Alexander Perfilyev, Ninna S Hansen, Maren Schrölkamp, Klaudia S Strasko, Camilla Scheele, Rasmus Ribel-Madsen, Brynjulf Mortensen, Sine W Jørgensen, Charlotte Ling, Allan Vaag
AIMS/HYPOTHESIS: Low birthweight (LBW) is associated with dysfunctions of adipose tissue and metabolic disease in adult life. We hypothesised that altered epigenetic and transcriptional regulation of adipose-derived stem cells (ADSCs) could play a role in programming adipose tissue dysfunction in LBW individuals. METHODS: ADSCs were isolated from the subcutaneous adipose tissue of 13 normal birthweight (NBW) and 13 LBW adult men. The adipocytes were cultured in vitro, and genome-wide differences in RNA expression and DNA methylation profiles were analysed in ADSCs and differentiated adipocytes...
September 14, 2016: Diabetologia
Ramanathan K Kasimanickam
The objective was to elucidate gene expression differences in uterus, caruncle, and cotyledon of ewes with subclinical pregnancy toxemia (SCPT) and healthy ewes, and to identify associated biological functions and pathways involved in pregnancy toxemia. On Day 136 (±1 day) post-breeding, ewes (n = 18) had body condition score (BCS; 1-5; 1, emaciated; 5, obese) assessed, and blood samples were collected for plasma glucose and β-hydroxybutyrate (BHBA) analyses. The ewes were euthanized, and tissue samples were collected from the gravid uterus and placentomes...
2016: Frontiers in Veterinary Science
Tatiana Kelil, Abhishek R Keraliya, Stephanie A Howard, Katherine M Krajewski, Marta Braschi-Amirfarzan, Jason L Hornick, Nikhil H Ramaiya, Sree Harsha Tirumani
Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer. Ultrasonography (US) and US-guided biopsy remain cornerstones in the initial workup of thyroid cancer...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Sylvia Otto, Kristin Jaeger, Frank D Kolodgie, Diana Muehlstaedt, Marcus Franz, Sabine Bischoff, Harald Schubert, Hans R Figulla, Renu Virmani, Tudor C Poerner
AIM: Peroxisome proliferator-activated receptor-gamma (PPARg) agonists have known pleiotropic cardiovascular effects with favourable properties in vascular remodeling, and specifically in suppression of vascular smooth muscle cell proliferation. A novel vascular stent coating using the PPARg ligand ciglitazone (CCS) was investigated regarding its effects on endothelialization after 7 and 28 days. METHODS: Microporous bare metal stents (BMS) were coated with ciglitazone by ultrasonic flux with a load of 255 μg ciglitazone/stent...
August 24, 2016: Oncotarget
Heli Routti, Roger Lille-Langøy, Mari K Berg, Trine Fink, Mikael Harju, Kurt Kristiansen, Pawel Rostkowski, Marte Rusten, Ingebrigt Sylte, Lene Øygarden, Anders Goksøyr
We studied interactions between polar bear peroxisome proliferator-activated receptor gamma (pbPPARG) and selected compounds using a luciferase reporter assay and predictions through molecular docking. Furthermore, we studied adipogenesis by liver and adipose tissue extracts from a polar bear and three synthetic mixtures of contaminants in murine 3T3-L1 preadipocytes and polar bear adipose tissue-derived stem cells (pbASCs). PCB153 and p,p'-DDE antagonized pbPPARG, although their predicted receptor-ligand affinity was weak...
October 4, 2016: Environmental Science & Technology
A Leońska-Duniec, I I Ahmetov, P Zmijewski
Frequent and regular physical activity has significant benefits for health, including improvement of body composition and help in weight control. Consequently, promoting training programmes, particularly in those who are genetically predisposed, is a significant step towards controlling the presently increasing epidemic of obesity. Although the physiological responses of the human body to exercise are quite well described, the genetic background of these reactions still remains mostly unknown. This review not only summarizes the current evidence, through a literature review and the results of our studies on the influence of gene variants on the characteristics and range of the body's adaptive response to training, but also explores research organization problems, future trends, and possibilities...
September 2016: Biology of Sport
Borja Bandera Merchan, Francisco José Tinahones, Manuel Macías-González
The PPAR nuclear receptor family has acquired great relevance in the last decade, which is formed by three different isoforms (PPARα, PPARβ/δ, and PPAR ϒ). Those nuclear receptors are members of the steroid receptor superfamily which take part in essential metabolic and life-sustaining actions. Specifically, PPARG has been implicated in the regulation of processes concerning metabolism, inflammation, atherosclerosis, cell differentiation, and proliferation. Thus, a considerable amount of literature has emerged in the last ten years linking PPARG signalling with metabolic conditions such as obesity and diabetes, cardiovascular disease, and, more recently, cancer...
2016: PPAR Research
Xin-Xing Zhu, Ya-Wei Yan, Demeng Chen, Chun-Zhi Ai, Xifeng Lu, Shan-Shan Xu, Shan Jiang, Gen-Shen Zhong, Dong-Bao Chen, Yi-Zhou Jiang
Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are involving in diverse cellular processes. However, their roles in reprogramming of gene expression profiles during lineage commitment and maturation of mesenchymal stem cells (MSCs) remain poorly understood. In the current study, we characterize the expression of a lncRNA, HoxA-AS3, during the differentiation of MSCs. We showed that HoxA-AS3 is increased upon adipogenic induction of MSCs, while HoxA-AS3 remains unaltered during osteogenic induction...
August 23, 2016: Oncotarget
Everardus J van Zoelen, Isabel Duarte, José M Hendriks, Sebastian P van der Woning
BACKGROUND: Patients suffering from osteoporosis show an increased number of adipocytes in their bone marrow, concomitant with a reduction in the pool of human mesenchymal stem cells (hMSCs) that are able to differentiate into osteoblasts, thus leading to suppressed osteogenesis. METHODS: In order to be able to interfere with this process, we have investigated in-vitro culture conditions whereby adipogenic differentiation of hMSCs is impaired and osteogenic differentiation is promoted...
2016: Stem Cell Research & Therapy
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