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Fat mass associated gene

Nikita V Khotskin, Alexandra V Plyusnina, Elizabeth A Kulikova, Ekaterina Y Bazhenova, Daryia V Fursenko, Ivan E Sorokin, Ilia Kolotygin, Pierre Mormede, Elena E Terenina, Oleg B Shevelev, Alexander V Kulikov
Lethal yellow (AY ) mutation causes obesity and type-2 diabetes in mice. Here we studied the effect of the AY mutation on the brain and behavior. The experiments were carried out on adult (11-12 weeks old) males of AY /a mice and their wild-type littermates (a/a). Mice of AY /a and a/a genotypes did not differ in their home cage activity, sleep, food and water consumption, learning ability in the Morris water maze, anxiety in the open field and elevated plus-maze, as well as in the level of monoamines, metabolites and some genes expression in the brain...
November 14, 2018: Behavioural Brain Research
Qiang Zhang, Xiayun Xia, Shixin Fang, Xiangzhen Yuan
BACKGROUND The distribution of fat mass and obesity-associated gene (FTO) genes rs9939609 and rs1421085 in obese and normal ethnic Mongolians was analyzed to investigate the association of FTO gene polymorphisms with obesity and metabolic syndrome in ethnic Mongolians. MATERIAL AND METHODS The genotypes of FTO genes rs9939609 and rs1421085 in 500 subjects were detected by allele-specific PCR (AS-PCR). General characteristics and clinical biochemical indicators were compared between the obesity group and the control group...
November 16, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Emad Yuzbashian, Golaleh Asghari, Mehdi Hedayati, Maryam Zarkesh, Parvin Mirmiran, Alireza Khalaj
We aimed to illustrate determinants of VDR gene expression in visceral and subcutaneous adipose tissue among individuals without diabetes. We gathered visceral and subcutaneous adipose tissues during an elective abdominal surgery form 33 morbidly obese (BMI > 40 kg/m2 ), 23 obese (BMI = 30-40 kg/m2 ), and 35 non-obese (BMI<30 kg/m2 ) participants who were free of diabetes. Participants were classified according to their degree of obesity. Before the surgery, habitual dietary intake, physical activity, 25(OH)D, body mass index (BMI), waist circumference (WC), and HOMA-IR was gathered...
November 6, 2018: Journal of Steroid Biochemistry and Molecular Biology
G Wolff, A E Taranko, I Meln, J Weinmann, T Sijmonsma, S Lerch, D Heide, A T Billeter, D Tews, D Krunic, P Fischer-Posovszky, B P Müller-Stich, S Herzig, D Grimm, M Heikenwälder, W W Kao, A Vegiopoulos
OBJECTIVE: Extracellular matrix remodeling is required for adipose expansion under increased caloric intake. In turn, inhibited expandability due to aberrant collagen deposition promotes insulin resistance and progression towards the metabolic syndrome. An emerging role for the small leucine-rich proteoglycan Lumican in metabolically driven nonalcoholic fatty liver disease sparks an interest in further understanding its role in diet-induced obesity and metabolic complications. METHODS: Whole body ablation of Lumican (Lum-/- ) gene and adeno-associated virus-mediated over-expression were used in combination with control or high fat diet to assess energy balance, glucose homeostasis as well as adipose tissue health and remodeling...
October 23, 2018: Molecular Metabolism
M Pilar Valdecantos, Laura Ruiz, Virginia Pardo, Luis Castro-Sanchez, Carmelo García-Monzón, Borja Lanzón, Javier Rupérez, Coral Barbas, Jaqueline Naylor, James L Trevaskis, Joseph Grimsby, Cristina M Rondinone, Ángela M Valverde
Non-alcoholic fatty liver disease (NAFLD) is associated with post-operative liver failure (PLF) and impaired liver regeneration. We investigated the effects of a glucagon-like peptide-1 (GLP-1) receptor agonist on NAFLD, PLF and liver regeneration in mice fed chow diet or methionine/choline-deficient diet (MCD) or high fat diet (HFD). Fc-GLP-1 decreased transaminases, reduced intrahepatic triglycerides (TG) and improved MCD-induced liver dysfuction. Macrophage/Kupffer cell-related markers were also reduced although Fc-GLP-1 increased expression of genes related to natural killer (NK), cytotoxic T lymphocytes and hepatic stellate cell (HSC) activation...
November 7, 2018: Scientific Reports
Ilse Yessabel Martinez Munoz, Eneida Del Socorro Camarillo Romero, Jose de Jesus Garduno Garcia
The rising prevalence of chronic diseases such as type 2 diabetes and cardiovascular diseases owing to fat mass excess has been described. In recent years, muscle function/dysfunction has become relevant in metabolic homeostasis. Irisin was described as an exercise-induced myokine. It is the product of type I membrane protein cleavage encoded by the fibronectin type III domain containing 5 (FNDC5) gene. The main beneficial function attributable to irisin is the change of subcutaneous and visceral adipose tissue into brown adipose tissue, with a consequential increase in thermogenesis...
2018: International Journal of Endocrinology
Rumana Yasmeen, Qiwen Shen, Aejin Lee, Jacob H Leung, Devan Kowdley, David J DiSilvestro, Lu Xu, Kefeng Yang, Andrei Maiseyeu, Naresh C Bal, Muthu Periasamy, Paolo Fadda, Ouliana Ziouzenkova
Adipokine leptin regulates neuroendocrine circuits that control energy expenditure, thermogenesis and weight loss. However, canonic regulators of leptin secretion, such as insulin and malonyl CoA, do not support these processes. We hypothesize that epiregulin (EREG), a growth factor that is secreted from fibroblasts under thermogenic and cachexia conditions, induces leptin secretion associated with energy dissipation. The effects of EREG on leptin secretion were studied ex vivo, in the intra-abdominal white adipose tissue (iAb WAT) explants, as well as in vivo, in WT mice with diet-induced obesity (DIO) and in ob/ob mice...
December 1, 2018: Journal of Endocrinology
Connor A Emdin, Amit V Khera, Krishna Aragam, Mary Haas, Mark Chaffin, Derek Klarin, Pradeep Natarajan, Alexander Bick, Seyedeh M Zekavat, Akihiro Nomura, Diego Ardissino, James G Wilson, Heribert Schunkert, Ruth McPherson, Hugh Watkins, Roberto Elosua, Matthew J Bown, Nilesh J Samani, Usman Baber, Jeanette Erdmann, Namrata Gupta, John Danesh, Danish Saleheen, Stacey Gabriel, Sekar Kathiresan
A genetic predisposition to higher waist-to-hip ratio adjusted for body mass index (WHRadjBMI), a measure of body fat distribution, associates with increased risk for type 2 diabetes. We conducted an exome-wide association study of coding variation in UK Biobank (405569 individuals) to identify variants that lower WHRadjBMI and protect against type 2 diabetes. We identified four variants in the gene ACVR1C , encoding the activin-receptor like kinase 7 receptor expressed on adipocytes and pancreatic beta cells, which independently associated with reduced WHRadjBMI: Asn150His (-0...
November 2, 2018: Diabetes
Tooru M Mizuno
Common genetic variants of the fat mass and obesity associated ( FTO ) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed. Earlier studies have focused on the role of hypothalamic FTO in the regulation of metabolism. However, recent studies suggest that expression of hepatic FTO is regulated by metabolic signals, such as nutrients and hormones, and altered FTO levels in the liver affect glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism...
November 1, 2018: Nutrients
Beatriz C Borges, Xingfa Han, Susan J Allen, David Garcia-Galiano, Carol F Elias
Hypothalamic neurons detect changes in circulating hormones such as leptin and insulin and put forward outputs to sustain energy and glucose homeostasis. Because leptin and insulin receptors colocalize in about 40-60% of neurons in the hypothalamus, we characterized the metabolic phenotype of mice with selective deletion of the InsR in LepR cells. LRΔInsR mice presented no difference in body weight and insulin levels, but increased fat mass. In the light phase, LRΔInsR mice exhibited increased food intake, locomotor activity, VCO2 and RER...
October 30, 2018: American Journal of Physiology. Endocrinology and Metabolism
Saeid Doaei, Naser Kalantari, Nastaran Keshavarz Mohammadi, Pantea Izadi, Maryam Gholamalizadeh, Hassan Eini-Zinab, Tuire Salonurmi, Alireza Mosavi Jarrahi, Shahram Rafieifar, Rahim Najafi, Mahnaz Sadeghypor, Ghasem Azizi Tabesh, Mark O Goodarzi
The role of FTO genotype in the effect of FTO gene expression level on change in body mass index and body composition has not been studied. This study aimed to investigate the role of FTO genotype in the association between change in the expression level of the FTO gene with changes in anthropometric measurements in obese and overweight adolescent boys. Eighty-four boys aged 12 to 16 years participated in this longitudinal study. A bioimpedance analyzer (BIA) was used to estimate percentage of body fat (%body fat) and percentage of skeletal muscle (%skeletal muscle)...
October 29, 2018: American Journal of Men's Health
Vincenzo Musolino, Sandra Palus, Celine Latouche, Micaela Gliozzi, Francesca Bosco, Federica Scarano, Saverio Nucera, Cristina Carresi, Miriam Scicchitano, Stephan von Haehling, Frederic Jaisser, Gerd Hasenfuss, Stefan D Anker, Vincenzo Mollace, Jochen Springer
AIMS: Cachexia is a severe consequence of cancer. Although cancer-induced heart atrophy leads to cardiac dysfunction and heart failure (HF), biomarkers for their diagnosis have not been identified. Neutrophil gelatinase-associated lipocalin (NGAL) is an aldosterone-responsive gene increased in HF. We studied NGAL and its association with aldosterone levels in a model of cancer cachexia-induced cardiomyopathy. METHODS AND RESULTS: Rats were injected with Yoshida 108 AH-130 hepatoma cells to induce tumour...
October 26, 2018: ESC Heart Failure
Daniel L Smith, Yongbin Yang, Tim R Nagy, Amit Patki, Joseph R Vasselli, Yiying Zhang, Stephanie L Dickinson, David B Allison
OBJECTIVE: Despite the known health benefits of weight loss among persons with obesity, observational studies have reported that cycles of weight loss and regain, or weight cycling, are associated with increased mortality. To study whether weight loss must be sustained to achieve health and longevity benefits, we performed a randomized controlled feeding study of weight cycling in mice. METHODS: In early adult life, obese mice were randomized to ad libitum feeding to sustain obesity, calorie restriction to achieve a "normal" or intermediate body weight, or weight cycling (repeated episodes of calorie restriction and ad libitum refeeding)...
November 2018: Obesity
Raffael Ott, Jens H Stupin, Kerstin Melchior, Karen Schellong, Thomas Ziska, Joachim W Dudenhausen, Wolfgang Henrich, Rebecca C Rancourt, Andreas Plagemann
BACKGROUND: Adiponectin critically contributes to metabolic homeostasis, especially by insulin-sensitizing action. Gestational diabetes mellitus (GDM) is characterized by insulin resistance leading to materno-fetal hyperglycemia and detrimental birth outcomes. By investigating paired subcutaneous (SAT) and visceral adipose tissue (VAT) as well as blood (cell) samples of GDM-affected (n = 25) vs. matched control (n = 30) mother-child dyads of the prospective "EaCH" cohort study, we addressed whether alterations of adiponectin plasma, mRNA, and DNA methylation levels are associated with GDM and offspring characteristics...
October 24, 2018: Clinical Epigenetics
Gudrun Valgerdur Skuladottir, Harpa Oskarsdottir, Claudia Pisanu, Marcus Sjödin, Johan Lindberg, Jessica Mwinyi, Helgi Birgir Schiöth
Purpose: Dietary macronutrient composition, stearoyl-CoA desaturase (SCD) activity indices, and primary bile acid (BA) concentrations are among the factors that have been associated with lipid metabolism and contributed to obesity. We investigated the association between the polymorphic expression of the fat mass and obesity-associated ( FTO ) gene and its relationship with SCD activity indices and primary BA concentrations after a low-fat meal. Subjects and methods: Blood plasma samples were collected from 56 young (20-36 years) healthy subjects with different rs9939609 FTO genotypes...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Cristina Oana Mǎrginean, Claudiu Mǎrginean, Lorena Elena Meliţ
Introduction: Childhood obesity is occurring at alarming rates in both developed and developing countries. "Obesogenic" environmental factors must be associated with variants of different risk alleles to determine polygenic or common obesity, and their impact depends on different developmental stages.The interaction between obesogenic environment and genetic susceptibility results in the so-called polygenic forms of obesity. In contrast, monogenic and syndromic obesity are not influenced by environmental events...
2018: Frontiers in Pediatrics
Paul Petrus, Niklas Mejhert, Patricia Corrales, Simon Lecoutre, Qian Li, Estela Maldonado, Agne Kulyté, Yamila Lopez, Mark Campbell, Juan R Acosta, Jurga Laurencikiene, Iyadh Douagi, Hui Gao, Concepción Martínez-Álvarez, Per Hedén, Kirsty L Spalding, Antonio Vidal-Puig, Gema Medina-Gomez, Peter Arner, Mikael Rydén
White adipose tissue (WAT) mass is determined by adipocyte size and number. While adipocytes are continuously turned over, the mechanisms controlling fat cell number in WAT upon weight changes are unclear. Herein, prospective studies of human subcutaneous WAT demonstrate that weight gain increases both adipocyte size and number, but the latter remains unaltered after weight loss. Transcriptome analyses associate changes in adipocyte number with the expression of 79 genes. This gene set is enriched for growth factors, out of which one, transforming growth factor-β3 (TGFβ3), stimulates adipocyte progenitor proliferation, resulting in a higher number of cells undergoing differentiation in vitro...
October 16, 2018: Cell Reports
Khadija El Jellas, Bente B Johansson, Karianne Fjeld, Aristotelis Antonopoulos, Heike Immervoll, Man H Choi, Dag Hoem, Mark E Lowe, Dominique Lombardo, Pål R Njølstad, Anne Dell, Eric Mas, Stuart M Haslam, Anders Molven
Carboxyl-ester lipase (CEL) is a pancreatic fat-digesting enzyme associated with human disease. Rare mutations in the CEL gene cause a syndrome of pancreatic exocrine and endocrine dysfunction denoted MODY8, whereas a recombined CEL allele increases the risk for chronic pancreatitis. Moreover, CEL has been linked to pancreatic ductal adenocarcinoma (PDAC) through a postulated oncofetal CEL variant termed feto-acinar pancreatic protein (FAPP). The monoclonal antibody mAb16D10 was previously reported to detect a glycotope in the highly O-glycosylated, mucin-like C-terminus of CEL/FAPP...
October 12, 2018: Journal of Biological Chemistry
Jeong Yoon Chang, Joo Hyun Park, Sung Eun Park, Jinyoung Shon, Yoon Jung Park
OBJECTIVE: Genetic variants at the fat mass- and obesity-associated (FTO) locus are strongly associated with obesity-related traits by regulating neighboring genes. Nevertheless, it is possible that FTO protein is directly involved in mechanisms regulating body composition and adiposity. Here, the in vivo biological functions of FTO in the risk for obesity were studied by reviewing murine models. METHODS: The effects of the locus-specific manipulations of the murine Fto gene on metabolic-related phenotypes in genetically modified mouse models were reviewed and summarized into the following three categories: growth and body composition, eating behaviors, and metabolic homeostasis...
November 2018: Obesity
Jiazhen Tang, Hongyi Zhou, Khushboo Sahay, Wenqiong Xu, Jing Yang, Wei Zhang, Weiqin Chen
BACKGROUND: Obesity and its associated morbidities represent the major and most rapidly expanding world-wide health epidemic. Recent genome-wide association studies (GWAS) reveal that single nucleotide polymorphism (SNP) variant in the Family with Sequence Similarity 13, Member A (FAM13A) gene is strongly associated with waist-hip ratio (WHR) with adjustment for body mass index (BMI) (WHRadjBMI). However, the function of FAM13A in adipose development and obesity remains largely uncharacterized...
October 9, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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