FTO Obesity Variant Circuitry and Adipocyte Browning in Humans

• Published in: The New England journal of medicine Vol. 373; no. 10; pp. 895 - 907
• Main Authors: Claussnitzer, Melina, Dankel, Simon N, Kim, Kyoung-Han, Quon, Gerald, Meuleman, Wouter, Haugen, Christine, Glunk, Viktoria, Sousa, Isabel S, Beaudry, Jacqueline L, Puviindran, Vijitha, Abdennur, Nezar A, Liu, Jannel, Svensson, Per-Arne, Hsu, Yi-Hsiang, Drucker, Daniel J, Mellgren, Gunnar, Hui, Chi-Chung, Hauner, Hans, Kellis, Manolis
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 03.09.2015
• Subjects: Adipocytes; Adipocytes - metabolism; ADIPOSE-TISSUE; ADULT OBESITY; Alleles; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Animals; Appetite; Base Sequence; Body fat; Body weight; BODY-MASS INDEX; Cell and Molecular Biology; Cell- och molekylärbiologi; CHILDHOOD; Clustered Regularly Interspaced Short Palindromic Repeats; Conserved sequence; CRISPR; Derepression; Epigenomics; Gastrointestinal surgery; GENE-EXPRESSION; Genes; Genetic Engineering; Genome editing; Genomes; Genomics; Haplotypes; Humans; IRX3; LOCUS; Mice; Mitochondria; Mitochondria - metabolism; Molecular Sequence Data; Obesity; Obesity - genetics; Obesity - metabolism; Phenotype; Physical activity; Proteins - genetics; RISK; RNA Editing; Thermogenesis; Thermogenesis - genetics; Thermogenesis - physiology; Weight control; Norway
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1502214

In this study, the authors used epigenetics, allelic activity, motif conservation, and other techniques to dissect the regulatory circuitry and mechanistic basis of the association between the FTO region and obesity. An adipocyte thermogenesis pathway that appears important was found. Obesity affects more than 500 million people worldwide and contributes to type 2 diabetes, cardiovascular disorders, and cancer. 1 Obesity is the result of a positive energy balance, whereby energy intake exceeds expenditure, resulting in the storage of energy, primarily as lipids in white adipocytes. Energy balance is modulated by food consumption and physical activity, as well as by the dissipation of energy as heat through constitutive thermogenesis in mitochondria-rich brown adipocytes in brown fat and through inducible thermogenesis in beige adipocytes in white fat. 2 – 6 Thermogenesis is triggered by mechanisms within the cells themselves or by the sympathetic nervous system . . .