The hepatic expression of the cell death-inducing DNA fragmentation factor A-like effector family (CIDEA, CIDEB, and CIDEC) genes is markedly upregulated in mouse models of obesity. We evaluated the expression of CIDE genes in liver of obese human subjects undergoing gastric bypass surgery (GBS), at the time of surgery and again 1 year later when subjects had lost 37.6 +/- 1.4% of their initial body weight. At the time of GBS, the expression of CIDEA (r(2) = 0.20, P = 0.04) and CIDEC (r(2) = 0.32, P = 0.01) was strongly correlated with BMI, whereas CIDEB was not (r(2) = 0.01, P = 0.81). One year after surgery, CIDEC expression had declined over 60% (P = 0.02), whereas CIDEA expression did not change (P = 0.20). These data demonstrate that, consistent with previous studies conducted in rodents, hepatic expression of CIDEA and CIDEC, but not CIDEB, is increased in obese humans. Moreover, the hepatic expression of CIDEC is downregulated by marked weight loss.