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Obesity and genes

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https://www.readbyqxmd.com/read/29224098/role-of-estrogens-in-the-regulation-of-liver-lipid-metabolism
#1
Brian T Palmisano, Lin Zhu, John M Stafford
Before menopause, women are protected from atherosclerotic heart disease associated with obesity relative to men. Sex hormones have been proposed as a mechanism that differentiates this risk. In this review, we discuss the literature around how the endogenous sex hormones and hormone treatment approaches after menopause regulate fatty acid, triglyceride, and cholesterol metabolism to influence cardiovascular risk.The important regulatory functions of estrogen signaling pathways with regard to lipid metabolism have been in part obscured by clinical trials with hormone treatment of women after menopause, due to different formulations, routes of delivery, and pairings with progestins...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29222412/ancestral-perinatal-obesogen-exposure-results-in-a-transgenerational-thrifty-phenotype-in-mice
#2
Raquel Chamorro-Garcia, Carlos Diaz-Castillo, Bassem M Shoucri, Heidi Käch, Ron Leavitt, Toshi Shioda, Bruce Blumberg
Ancestral environmental exposures to non-mutagenic agents can exert effects in unexposed descendants. This transgenerational inheritance has significant implications for understanding disease etiology. Here we show that exposure of F0 mice to the obesogen tributyltin (TBT) throughout pregnancy and lactation predisposes unexposed F4 male descendants to obesity when dietary fat is increased. Analyses of body fat, plasma hormone levels, and visceral white adipose tissue DNA methylome and transcriptome collectively indicate that the F4 obesity is consistent with a leptin resistant, thrifty phenotype...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29221790/fam3-gene-family-a-promising-therapeutical-target-for-nafld-and-type-2-diabetes
#3
REVIEW
Zhang Xiaoyan, Weili Yang, Junpei Wang, Yuhong Meng, Youfei Guan, Jichun Yang
Non-alcoholic fatty liver disease (NAFLD) and diabetes are severe public health issues worldwide. The Family with sequence similarity 3 (FAM3) gene family consists of four members designated as FAM3A, FAM3B, FAM3C and FAM3D, respectively. Recently, there had been increasing evidence that FAM3A, FAM3B and FAM3C are important regulators of glucose and lipid metabolism. FAM3A expression is reduced in the livers of diabetic rodents and NAFLD patients. Hepatic FAM3A restoration activates ATP-P2 receptor-Akt and AMPK pathways to attenuate steatosis and hyperglycemia in obese diabetic mice...
December 5, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29220798/aegeline-inspired-synthesis-of-novel-amino-alcohol-and-thiazolidinedione-hybrids-with-antiadipogenic-activity-in-3t3-l1-cells
#4
Sabbu Satish, Ankita Srivastava, Pragya Yadav, Salil Varshney, Rakhi Choudhary, Vishal M Balaramnavar, Tadigoppula Narender, Anil Nilkanth Gaikwad
Excess adiposity is a hallmark of obesity, which is caused due to an imbalance between energy intake and energy consumed. Obesity is often associated with several metabolic disorders like dyslipidemia, cardiovascular diseases and type 2 diabetes. Earlier, our group had reported natural product Aegeline (amino-alcohol) isolated from the plant Aegle marmelos as an anti-diabetic and anti-dyslipidemic compound. With this background, we synthesized a series of novel amino alcohol and thiazolidinedione hybrid molecules and studied their antiadipogenic activity...
November 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29220752/genomic-characterization-of-the-porcine-crtc3-and-the-effects-of-a-non-synonymous-mutation-p-v515f-on-lean-meat-production-and-belly-fat
#5
S H Lee, M H Hur, E A Lee, K C Hong, J M Kim
cAMP-responsive element-binding protein (CREB)-regulated transcriptional coactivator 3 (CRTC3) is well known to be related to obesity in humans and mice. However, the effects of CRTC3 have not been studied in pigs. Here, we characterized the structure of the porcine CRTC3 gene and identified single nucleotide polymorphisms (SNPs) in its coding region. Moreover, mRNA expression profiles of CRTC3 in muscle and fat tissues were examined. Of the 40 identified SNPs, the p.V515F mutation, located on exon 16, was genotyped in 368 Yorkshire pigs...
November 20, 2017: Meat Science
https://www.readbyqxmd.com/read/29220676/penetrance-of-polygenic-obesity-susceptibility-loci-across-the-body-mass-index-distribution
#6
Arkan Abadi, Akram Alyass, Sebastien Robiou du Pont, Ben Bolker, Pardeep Singh, Viswanathan Mohan, Rafael Diaz, James C Engert, Salim Yusuf, Hertzel C Gerstein, Sonia S Anand, David Meyre
A growing number of single-nucleotide polymorphisms (SNPs) have been associated with body mass index (BMI) and obesity, but whether the effects of these obesity-susceptibility loci are uniform across the BMI distribution remains unclear. We studied the effects of 37 BMI-associated SNPs in 75,230 adults of European ancestry across BMI percentiles by using conditional quantile regression (CQR) and meta-regression (MR) models. The effects of nine SNPs (24%)-rs1421085 (FTO; p = 8.69 × 10-15), rs6235 (PCSK1; p = 7...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29220587/fto-gene-affects-obesity-and-breast-cancer-through-similar-mechanisms-a-new-insight-into-the-molecular-therapeutic-targets
#7
M E Akbari, M Gholamalizadeh, S Doaei, F Mirsafa
OBJECTIVES: This review focused on the possible mediatory role of the FTO in the association between obesity and breast cancer. METHOD: All articles published in English from June 1990 to January 2017 were studied. The search terms used were FTO gene, FTO polymorphism, breast cancer, and obesity. Inclusion criteria consisted of assessment of the relationship between FTO polymorphisms and/or FTO expression level with obesity and/or breast cancer as a primary outcome...
December 8, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29220483/prenatal-exposure-to-bisphenol-a-disrupts-naturally-occurring-bimodal-dna-methylation-at-proximal-promoter-of-fggy-an-obesity-relevant-gene-encoding-a-carbohydrate-kinase-in-gonadal-white-adipose-tissues-of-cd-1-mice
#8
Julia A Taylor, Keiko Shioda, Shino Mitsunaga, Shiomi Yawata, Brittany M Angle, Susan C Nagel, Frederick S Vom Saal, Toshi Shioda
Exposure of mammalian fetuses to endocrine disruptors can increase the risk of adult-onset diseases. For example, we previously showed that exposure of mouse fetuses to bisphenol A (BPA) caused adult-onset obesity. To obtain insights into roles of epigenetic changes in the delayed toxic effects of endocrine disruption, we determined effects of fetal mouse exposure to BPA on genome-wide DNA methylation and mRNA expression in gonadal white adipose tissues by deep sequencing (MBD-seq and RNA-seq), bisulfite pyrosequencing, and real-time qPCR...
December 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/29218110/downregulation-of-cathepsin-g-reduces-the-activation-of-cd4-t-cells-in-murine-autoimmune-diabetes
#9
Fang Zou, Xiaoyang Lai, Jing Li, Shuihong Lei, Lei Hu
Type 1 diabetes mellitus (T1DM) is an autoimmune disease due to progressive injury of islet cells mediated by T lymphocytes (T cells). Our previous studies have shown that only cathepsin G (CatG), not other proteases, is involved in the antigen presentation of proinsulin, and if the presentation is inhibited, the activation of CD4+ T cells induced by proinsulin is alleviated in T1DM patients, and CatG-specific inhibitor reduces the activation of CD4+ cells induced by proinsulin in T1DM patients. Therefore, we hypothesize that CatG may play an important role in the activation of CD4+ T cells in T1DM...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29217834/gender-specific-alteration-of-energy-balance-and-circadian-locomotor-activity-in-the-crtc1-knockout-mouse-model-of-depression
#10
Clara Rossetti, Daniel Sciarra, Jean-Marie Petit, Chin B Eap, Olivier Halfon, Pierre J Magistretti, Benjamin Boutrel, Jean-René Cardinaux
Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1's role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29217518/enhancement-of-mammary-tumor-growth-by-igfbp-3-involves-impaired-t-cell-accumulation
#11
Tiffany Scully, Carolyn Scott, Sue Mei Firth, Lisa M Sedger, John E Pintar, Stephen Twigg, Robert C Baxter
Epidemiological studies show an association between obesity and poor breast cancer prognosis. We previously demonstrated that global IGFBP-3 deficiency, in IGFBP-3-null mice, resulted in a 50% reduction in mammary tumor growth over 3 weeks relative to tumors in wild-type C57BL/6 mice. This growth reduction was ameliorated by high-fat feeding-induced obesity. This study aimed to examine how IGFBP-3 promotes tumor growth by influencing the immune tumor microenvironment in healthy and obese mice. Syngeneic EO771 cells, which lack detectable IGFBP-3 expression, were grown as orthotopic tumors in wild-type and IGFBP-3-null C57BL/6 mice placed on either a control chow or high-fat diet, and examined by quantitative PCR and immunohistochemistry...
December 7, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29217499/severe-early-onset-obesity-due-to-a-novel-missense-mutation-in-exon-3-of-leptin-gene-in-an-infant-from-northwest-india
#12
Devi Dayal, Keerthivasan Seetharaman, Inusha Panigrahi, Muthuvel Balasubramaniyan, Ashish Agarwal
Monogenic obesity caused by mutations in one of the several genes involved in the control of hunger and satiety is a rare cause of early-onset obesity (EOO). The most common of the single gene alterations affect the LEP gene resulting in congenital leptin deficiency that manifests as intense hyperphagia, EOO and severe obesity associated hormonal and metabolic alterations. Only eight mutations of LEP gene associated with congenital leptin deficiency in humans have been described. In this study, we report a novel homozygous missense mutation in exon 3 of the LEP gene (chr7:127894610;c...
December 8, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29217450/cadm2-regulates-body-weight-and-energy-homeostasis-in-mice
#13
Xin Yan, Zhen Wang, Vanessa Schmidt, Anton Gauert, Thomas E Willnow, Matthias Heinig, Matthew N Poy
OBJECTIVE: Obesity is strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI) and multiple loci near Cell adhesion molecule2 (CADM2), which encodes a mediator of synaptic signaling enriched in the brain. Here we sought to further understand the role of Cadm2 in the pathogenesis of hyperglycemia and weight gain...
November 22, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29217197/effect-of-lncrna-hoxa11-as1-on-adipocyte-differentiation-in-human-adipose-derived-stem-cells
#14
Nuerbiye Nuermaimaiti, Jie Liu, Xiaodi Liang, Yi Jiao, Dan Zhang, Ling Liu, Xuanyu Meng, Yaqun Guan
AIMS: To determine the role of lncRNA HOXA11-AS1 on adipocyte differentiation. METHODS: Human adipose-derived stem cells (hADSCs) were isolated from adipose tissues of patients and cultured in vitro, followed by knockdown of HOXA11-AS1. Then, adipocyte differentiation and expression of adipogenic-related genes (CEBP-α, DGAT2, CIDEC, and perilipin) were measured by RT-qPCR and Western blot. RESULTS: We demonstrated that knockdown of HOXA11-AS1 inhibited adipocyte differentiation, leading to suppression of adipogenic-related gene (CEBP-α, DGAT2, CIDEC, and perilipin) transcription, as well as decreased lipid accumulation in hADSCs...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29217172/nobiletin-induces-brown-adipocyte-like-phenotype-and-ameliorates-stress-in-3t3-l1-adipocytes
#15
Jameel Lone, Hilal Ahmad Parray, Jong Won Yun
Browning of white adipocytes (beiging) is an attractive therapeutic strategy against obesity and its associated metabolic complications. Nobiletin (NOB) is a polymethoxylated flavone present in Citrus fruits and has been reported to have anti-obesity effects. Here, we report that nobiletin exerts dual modulatory effects on adipocytes via induction of browning in 3T3-L1 white adipocytes and amelioration of stress in adipocytes. Nobiletin-induced beiging was investigated by determining expression levels of beige-specific genes and proteins by RT-PCR and immunoblot analysis, respectively...
December 4, 2017: Biochimie
https://www.readbyqxmd.com/read/29216354/high-prevalence-of-rare-monogenic-forms-of-obesity-in-obese-guadeloupean-afro-caribbean-children
#16
Lydia Foucan, Laurent Larifla, Emmanuelle Durand, Christine Rambhojan, Christophe Armand, Carl-Thony Michel, Rachel Billy, Véronique Dhennin, Franck De Graeve, Iandry Rabearivelo, Olivier Sand, Jean-Marc Lacorte, Philippe Froguel, Amélie Bonnefond
Context: The population from Guadeloupe Island exhibits high prevalence of obesity. Objective: We aimed to investigate whether rare genetic mutations in genes involved in monogenic obesity (or diabetes) might be causal in this population of Afro-Caribbean ancestry. Design and setting: This was a secondary analysis of a study on obesity conducted in schoolchildren from Guadeloupe in 2013, which aimed to assess the changes in children profiles after a lifestyle intervention program...
December 5, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29214176/human-gut-microbiota-associated-with-obesity-in-chinese-children-and-adolescents
#17
Ya-Ping Hou, Qing-Qing He, Hai-Mei Ouyang, Hai-Shan Peng, Qun Wang, Jie Li, Xiao-Fei Lv, Yi-Nan Zheng, Shao-Chuan Li, Hai-Liang Liu, Ai-Hua Yin
Objective: To investigate the gut microbiota differences of obese children compared with the control healthy cohort to result in further understanding of the mechanism of obesity development. Methods: We evaluated the 16S rRNA gene, the enterotypes, and quantity of the gut microbiota among obese children and the control cohort and learned the differences of the gut microbiota during the process of weight reduction in obese children. Results: In the present study, we learned that the gut microbiota composition was significantly different between obese children and the healthy cohort...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29213261/antibiotic-induced-alterations-in-gut-microbiota-are-associated-with-changes-in-glucose-metabolism-in-healthy-mice
#18
Richard R Rodrigues, Renee L Greer, Xiaoxi Dong, Karen N DSouza, Manoj Gurung, Jia Y Wu, Andrey Morgun, Natalia Shulzhenko
The gut microbiome plays an important role in health and disease. Antibiotics are known to alter gut microbiota, yet their effects on glucose tolerance in lean, normoglycemic mice have not been widely investigated. In this study, we aimed to explore mechanisms by which treatment of lean mice with antibiotics (ampicillin, metronidazole, neomycin, vancomycin, or their cocktail) influences the microbiome and glucose metabolism. Specifically, we sought to: (i) study the effects on body weight, fasting glucose, glucose tolerance, and fasting insulin, (ii) examine the changes in expression of key genes of the bile acid and glucose metabolic pathways in the liver and ileum, (iii) identify the shifts in the cecal microbiota, and (iv) infer interactions between gene expression, microbiome, and the metabolic parameters...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29212764/aberrant-dna-methylation-of-pregnane-x-receptor-underlies-metabolic-gene-alterations-in-the-diabetic-kidney
#19
Atsushi Watanabe, Takeshi Marumo, Wakako Kawarazaki, Mitsuhiro Nishimoto, Nobuhiro Ayuzawa, Kohei Ueda, Daigoro Hirohama, Toshiya Tanaka, Shintaro Yagi, Satoshi Ota, Genta Nagae, Hiroyuki Aburatani, Hiroo Kumagai, Toshiro Fujita
Epigenetic abnormalities have been suggested to mediate metabolic memory observed in diabetic complications. We have shown that epigenetic alterations may induce persistent phenotypic changes in the proximal tubules of the diabetic kidneys. In this study, we show that pregnane X receptor (PXR), a xenobiotic nuclear receptor, is epigenetically altered and upregulated, and may have a possible function in the diabetic kidney. PXR has been shown to play a critical role in metabolic changes in obesity and diabetes; however, its distribution and function in the kidney are unknown...
December 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29212543/gene-gravity-like-algorithm-for-disease-gene-prediction-based-on-phenotype-specific-network
#20
Limei Lin, Tinghong Yang, Ling Fang, Jian Yang, Fan Yang, Jing Zhao
BACKGROUND: Polygenic diseases are usually caused by the dysfunction of multiple genes. Unravelling such disease genes is crucial to fully understand the genetic landscape of diseases on molecular level. With the advent of 'omic' data era, network-based methods have prominently boosted disease gene discovery. However, how to make better use of different types of data for the prediction of disease genes remains a challenge. RESULTS: In this study, we improved the performance of disease gene prediction by integrating the similarity of disease phenotype, biological function and network topology...
December 6, 2017: BMC Systems Biology
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