An understanding of the mechanisms underlying body-weight regulation is crucial to tackle the growing problem of obesity. Recent technological advances in the analysis of genetic variation have given novel insights into the molecular basis of common disease. In particular, genomic variants in the fat mass and obesity-associated (FTO) gene have been consistently associated with human adiposity and metabolic disorders. Studies of the product of this previously mysterious gene have formed a vanguard in the quest to turn statistical association into hard biology. In this review, we examine data from human genetic and murine studies that explore the potential role of FTO, a member of the Fe(II)- and 2-oxoglutarate-dependent oxygenase superfamily, in the regulation of energy homeostasis and metabolism.
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