ABSTRACT
MELKAYE G. MELKA, JESSE GILLIS, MANON BERNARD, MICHAL ABRAHAMOWICZ, M. MALLAR CHAKRAVARTY, GABRIEL T. LEONARD, MICHEL PERRON, LOUIS RICHER, SUZANNE VEILLETTE, TOBIAS BANASCHEWSKI, GARETH J. BARKER, CHRISTIAN BÜCHEL, PATRICIA CONROD, HERTA FLOR, ANDREAS HEINZ, HUGH GARAVAN, RÜDIGER BRÜHL, KARL MANN, ERIC ARTIGES, ANBARASU LOURDUSAMY, MARK LATHROP, EVA LOTH, YANNICK SCHWARTZ, VINCENT FROUIN, MARCELLA RIETSCHEL, MICHAEL N. SMOLKA, ANDREAS STRÖHLE, JÜRGEN GALLINAT, MAREN STRUVE, EVA LATTKA, MELANIE WALDENBERGER, GUNTER SCHUMANN, PAUL PAVLIDIS, DANIEL GAUDET, TOMÁŠ PAUS, AND ZDENKA PAUSOVA
13.1 INTRODUCTION
The fat mass and obesity-associated gene (FTO) is a well-replicated gene locus of obesity (1-4). It was originally identified as a gene locus of type-2 diabetes, and only later it was discovered that it increases risk of this disease through its primary effect on adiposity (1). However, the mechanisms
through which FTO may increase adiposity are still not clear. In vitro studies suggest that FTO encodes 2-oxoglutarate-dependent nucleic-acid demethylase that may regulate gene expression (5-7). Beginning from early embryogenesis, the gene is expressed throughout the body and the brain (5,8,9). The relatively high expression of FTO in the adult hypothalamus, a brain structure regulating energy balance, suggested that FTO might influence adiposity through its impact on energy homeostasis. Conflicting results of both human and animal studies exist, however, as to whether the gene influences either food intake or energy expenditure in a way that would increase risk for obesity [reviewed in (3,4)].
