Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism

Individuals with a common variant of the FTO gene, which encodes an enzyme that modifies mRNAs, are more likely to become obese both as children and as adults. Wang et al. found that mice lacking FTO in adipocytes became more obese on a high-fat diet than did control mice. The deficiency of FTO in adipocytes resulted in increased extracellular lipolysis, which provided more fatty acids for uptake by adipose tissue, and in decreased intracellular lipolysis, which favored the storage of fatty acids in adipose tissue. Without FTO, adipose tissue produced less Angptl4, an adipokine that stimulates intracellular lipolysis. Thus, FTO in adipocytes affects body weight by regulating the translation of Angptl4 in adipose tissue.