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obesity genetics

Nienke M van Loon, Roelof Ottenhoff, Sander Kooijman, Martina Moeton, Saskia Scheij, Reinout L P Roscam Abbing, Marion J J Gijbels, Johannes H M Levels, Vincenzo Sorrentino, Jimmy F P Berbée, Patrick C N Rensen, Noam Zelcer
OBJECTIVE: The E3 ubiquitin ligase IDOL (inducible degrader of the LDLR [LDL (low-density lipoprotein) receptor]) is a post-transcriptional regulator of LDLR abundance. Model systems and human genetics support a role for IDOL in regulating circulating LDL levels. Whether IDOL plays a broader metabolic role and affects development of metabolic syndrome-associated comorbidities is unknown. APPROACH AND RESULTS: We studied WT (wild type) and Idol ( -/ - ) (Idol-KO) mice in 2 models: physiological aging and diet-induced obesity...
June 14, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Rong Chen, Shiying Chen, Tingxing Zhang, Jiabing Lin, Chunyu Wan, Zhou Chen, Huangyuan Li, Yan Ding, Siying Wu
OBJECTIVE: To understand the main environmental factors of hypertension, and to explore the relationship between hypertension and leukocyte long noncoding RNA. METHODS: A case-control study was conducted in a hospital in Fuzhou City by using stratified random sampling method between Nov. 2014 and Jun. 2015 including 382 essential hypertension patients and 382 control subjects. The related surveys included questionnaire investigation, physical examination and laboratory detection...
November 2017: Wei Sheng Yan Jiu, Journal of Hygiene Research
Dhite Bayu Nugroho, Koji Ikeda, Agian Jeffilano Barinda, Donytra Arby Wardhana, Keiko Yagi, Keishi Miyata, Yuichi Oike, Ken-Ichi Hirata, Noriaki Emoto
Adipose tissue (AT) contains well-developed vascular networks. Pathological AT expansion often accompany the reduction in AT blood vessels, which further exacerbates adipocyte dysfunction due to hypoxia; however, it remains unclear whether AT vascular rarefaction is simply secondary to adipocyte hypertrophy, or if there is an actively regulated pathway that mediates impaired AT angiogenesis in obesity. We searched for growth factors whose expression in AT is down-regulated in obesity; accordingly, we identified neuregulin-4 (Nrg4), a member of the EGF family of proteins...
June 11, 2018: Biochemical and Biophysical Research Communications
Chao-Qiang Lai, Caren E Smith, Laurence D Parnell, Yu-Chi Lee, Dolores Corella, Paul Hopkins, Bertha A Hidalgo, Stella Aslibekyan, Michael A Province, Devin Absher, Donna K Arnett, Katherine L Tucker, Jose M Ordovas
Background: The putative functional variant -265T>C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity. Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction. Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (<22 g/d) or high-SFA diet (≥22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS)...
June 12, 2018: American Journal of Clinical Nutrition
Yann C Klimentidis, David A Raichlen, Jennifer Bea, David O Garcia, Nathan E Wineinger, Lawrence J Mandarino, Gene E Alexander, Zhao Chen, Scott B Going
BACKGROUND/OBJECTIVES: Physical activity (PA) protects against a wide range of diseases. Habitual PA appears to be heritable, motivating the search for specific genetic variants that may inform efforts to promote PA and target the best type of PA for each individual. SUBJECTS/METHODS: We used data from the UK Biobank to perform the largest genome-wide association study of PA to date, using three measures based on self-report (nmax  = 377,234) and two measures based on wrist-worn accelerometry data (nmax  = 91,084)...
June 13, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Erik Ingelsson, Mark I McCarthy
Type 2 diabetes mellitus (T2D) and obesity already represent 2 of the most prominent risk factors for cardiovascular disease, and are destined to increase in importance given the global changes in lifestyle. Ten years have passed since the first round of genome-wide association studies for T2D and obesity. During this decade, we have witnessed remarkable developments in human genetics. We have graduated from the despair of candidate gene-based studies that generated few consistently replicated genotype-phenotype associations, to the excitement of an exponential harvest of loci robustly associated with medical outcomes through ever larger genome-wide association study meta-analyses...
June 2018: Circulation. Genomic and precision medicine
Heike Vogel, Anne Kamitz, Nicole Hallahan, Sandra Lebek, Tanja Schallschmidt, Wenke Jonas, Markus Jähnert, Pascal Gottmann, Lisa Zellner, Timo Kanzleiter, Mareike Damen, Delsi Altenhofen, Ralph Burkhardt, Simone Renner, Maik Dahlhoff, Eckhard Wolf, Timo D Müller, Matthias Blüher, Hans-Georg Joost, Alexandra Chadt, Hadi Al-Hasani, Annette Schürmann
To explore the genetic determinants of obesity and type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone NZO mouse strain with four different lean strains (B6, DBA, C3H, 129P2) which vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 QTL for obesity, 190 QTL for diabetes-related traits, and 100 QTL for plasma metabolites in the outcross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data...
June 8, 2018: Human Molecular Genetics
Maisa C Martins, Janet Trujillo, Ana Amélia Freitas-Vilela, Dayana R Farias, Eliane L Rosado, Cláudio J Struchiner, Gilberto Kac
Genetic variants associated with dietary intake may be important as factors underlying the development of obesity. We investigated the associations between the obesity candidate genes (fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), leptin (LEP) and leptin receptor) and total energy intake and percentage of energy from macronutrients and ultra-processed foods before and during pregnancy. A sample of 149 pregnant women was followed up in a prospective cohort in Rio de Janeiro, Brazil. A FFQ was administered at 5-13 and 30-36 weeks of gestation...
June 12, 2018: British Journal of Nutrition
Abdullah Hakan Karadoğan, Hilal Arikoglu, Fatma Göktürk, Funda İşçioğlu, Süleyman Hilmi İpekçi
BACKGROUND: The phosphatidylinositol 3-kinase p85 alpha regulatory subunit 1 gene (PIK3R1) encodes the PIK3R1 protein, which plays a direct role in insulin signaling. PIK3R1 (p85 regulatory subunit) connects firmly with the p110 catalytic subunit, and together these proteins form the phosphatidylinositol 3-kinase (PI3K) protein. PI3K is a key protein in the Akt signaling pathway, which regulates cell survival, growth, differentiation, glucose trafficking, and utilization. Defects in the insulin signaling cascade play an important role in the development of insulin resistance, which shares a common genetic basis for metabolic diseases such as type 2 diabetes (T2D), obesity and cardiovascular diseases...
June 8, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Alexis C Wood, Shabnam Momin, Mackenzie Senn, Sheryl O Hughes
PURPOSE OF REVIEW: Current feeding advice to prevent pediatric obesity focuses on caregiver feeding behaviors. This review integrates newer data showing that child appetitive traits also have a genetic component. RECENT FINDINGS: Caregiver feeding behaviors robustly correlate with child eating behaviors; however, there is also a strong heritable component. The satiety cascade delineates the biological drive underlying hunger, satiation, and satiety. Innate individual differences exist for the components of the satiety cascade, which may explain the heritability of child eating behaviors...
March 2018: Current Nutrition Reports
Brett MacFarlane
Gastroesophageal reflux disease (GERD) is a common gastrointestinal diagnosis, a leading reason for endoscopy and cause of potentially serious complications, resulting in significant individual and system-wide health burden. Approximately one quarter of people living in western countries have experienced GERD, and the prevalence appears to be on the rise. Risk factors for GERD include hiatus hernia, obesity, high-fat diet, tobacco smoking, alcohol consumption, pregnancy, genetics, and some medications. The cardinal symptoms of GERD are troublesome heartburn and regurgitation...
2018: Integrated Pharmacy Research and Practice
Graeme I Lancaster, Darren C Henstridge
Alterations to body composition (fat or lean mass), metabolic parameters such as whole-body oxygen consumption, energy expenditure, and substrate utilization, and behaviors such as food intake and physical activity can provide important information regarding the underlying mechanisms of disease. Given the importance of body composition and metabolism to the development of obesity and its subsequent sequelae, it is necessary to make accurate measures of these parameters in the pre-clinical research setting. Advances in technology over the past few decades have made it possible to derive these measures in rodent models in a non-invasive and longitudinal fashion...
May 24, 2018: Journal of Visualized Experiments: JoVE
Marwan El Ghoch, Paola Vittoria Bazzani, Simona Calugi, Riccardo Dalle Grave
Spinal muscular atrophy is a genetic neuromuscular disease characterised by muscle atrophy, hypotonia, weakness, and progressive paralysis. Usually, these patients display increased fat mass deposition and reductions in fat-free mass and resting energy expenditure-an unfavourable condition that facilitates the development of obesity. However, weight management of these patients remains poorly described. Hence, the aim of this case report was to describe the clinical presentation and weight management of a 31-year-old male patient with spinal muscular atrophy type III, class I obesity, and metabolic syndrome treated for 1 year by means of a personalised multistep cognitive-behavioural treatment for obesity...
2018: Case Reports in Medicine
Marion Bretault, Claire Carette, Charles Barsamian, Sébastien Czernichow
Hypothalamic obesity (HO) is a rare and serious disease of various origins: tumor, traumatism, radiotherapy, vascular, genetic, or even psychotropic drug use. HO usually begins in childhood with eating disorders and progresses with an aggregate of severe comorbidities. Transition from pediatric to adult health care is a critical period to assure weight stability and a good management of comorbidities. In case of loss to follow-up, there is an increased risk of major weight gain and long-term complications with severe obesity...
2018: Endocrine Development
Cristiano A Köhler, Evangelos Evangelou, Brendon Stubbs, Marco Solmi, Nicola Veronese, Lazaros Belbasis, Beatrice Bortolato, Matias C A Melo, Camila A Coelho, Brisa S Fernandes, Mark Olfson, John P A Ioannidis, André F Carvalho
The development of depression may involve a complex interplay of environmental and genetic risk factors. PubMed and PsycInfo databases were searched from inception through August 3, 2017, to identify meta-analyses and Mendelian randomization (MR) studies of environmental risk factors associated with depression. For each eligible meta-analysis, we estimated the summary effect size and its 95% confidence interval (CI) by random-effects modeling, the 95% prediction interval, heterogeneity with I2 , and evidence of small-study effects and excess significance bias...
May 25, 2018: Journal of Psychiatric Research
Jun Namkung, Ko Eun Shong, Hyeongseok Kim, Chang Myung Oh, Sangkyu Park, Hail Kim
BACKGROUND: Hepatic steatosis is caused by metabolic stress associated with a positive lipid balance, such as insulin resistance and obesity. Previously we have shown the anti-obesity effects of inhibiting serotonin synthesis, which eventually improved insulin sensitivity and hepatic steatosis. However, it is not clear whether serotonin has direct effect on hepatic lipid accumulation. Here, we showed the possibility of direct action of serotonin on hepatic steatosis. METHODS: Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 to inhibit serotonin synthesis and fed with high fat diet (HFD) or high carbohydrate diet (HCD) to induce hepatic steatosis...
April 25, 2018: Diabetes & Metabolism Journal
Natassia Rodrigo, Sarah J Glastras
Gestational diabetes mellitus (GDM) is a common complication of pregnancy; its rising incidence is a result of increased maternal obesity and older maternal age together with altered diagnostic criteria identifying a greater proportion of pregnant women with GDM. Its consequences are far-reaching, associated with poorer maternal and neonatal outcomes compared to non-GDM pregnancies, and GDM has implications for metabolic health in both mother and offspring. Objective markers to identify women at high risk for the development of GDM are useful to target therapy and potentially prevent its development...
May 23, 2018: Journal of Clinical Medicine
Paola Dongiovanni, Marica Meroni, Rosellina M Mancina, Guido Baselli, Raffaela Rametta, Serena Pelusi, Ville Männistö, Anna L Fracanzani, Sara Badiali, Luca Miele, Stefania Grimaudo, Salvatore Petta, Elisabetta Bugianesi, Giorgio Soardo, Silvia Fargion, Jussi Pihlajamäki, Stefano Romeo, Luca Valenti
Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver damage and has a strong genetic component. The rs4841132 G>A variant, modulating the expression of protein phosphatase 1 regulatory subunit 3B ( PPP1R3B ), which is involved in glycogen synthesis, has been reported to reduce the risk of NAFLD but at the same time may favor liver disease by facilitating glycogen accumulation. The aim of this study was to assess the impact of rs4841132 on development of histologic steatosis and fibrosis in 1,388 European individuals in a liver biopsy cohort, on NAFLD hepatocellular carcinoma in a cross-sectional Italian cohort (n = 132 cases), and on liver disease at the population level in the United Kingdom Biobank cohort...
June 2018: Hepatology Communications
Bruno Ramos-Molina, María Molina-Vega, José C Fernández-García, John W Creemers
Prader⁻Willi syndrome (PWS) is a complex genetic disorder that, besides cognitive impairments, is characterized by hyperphagia, obesity, hypogonadism, and growth impairment. Proprotein convertase subtilisin/kexin type 1 ( PCSK1 ) deficiency, a rare recessive congenital disorder, partially overlaps phenotypically with PWS, but both genetic disorders show clear dissimilarities as well. The recent observation that PCSK1 is downregulated in a model of human PWS suggests that overlapping pathways are affected...
June 7, 2018: Genes
Feng Gao, Tian-Run Lv, Jin-Chun Zhou, Xiao-Dong Qin
BACKGROUND: Obesity affects bone health to varying degrees, depending on the skeletal site (weight-bearing or non-weight-bearing) and compartment (cortical or trabecular), and is a risk factor for orthopedic disorders, including bone fractures. However, the effect and mechanisms of obesity on healing of bone fracture is little understood. METHODS: The healing bone fractures of the tibia in genetically obese mice was evaluated relative to normal mice at weekly intervals for 28 days using X-ray scans, hematoxylin and eosin (H&E) stain, and alcian blue (AB) stain...
June 8, 2018: Journal of Orthopaedic Surgery and Research
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