Cholesteryl Ester Transfer Protein (CETP) is a plasma protein that mediates the exchange of triglycerides for esterified cholesterol from HDL to the apoB-lipoproteins. In this way, CETP promotes reduction of plasma HDL-cholesterol and, thus, increases the risk of atherosclerosis. Recently, we found that CETP expressing mice (CETP-Tg) present lower adipose tissue mass than non-expressing controls. In this work we investigated possible mechanisms to explain these findings. The animal protocol was approved by the State University of Campinas Committee for Ethics in Animal Research under the protocol # 1607-1. CETP-Tg and NTg control mice (C57/BL6 background) were fed with chow diet from weaning. Samples were obtained post euthanasia, when mice were 5 month old. CETP-Tg mice had reduced perigonadal (-29%) and subcutaneous (-27%) fat depots that could not be explained by differences in fat intake and excretion. Adipose tissue (perigonadal and subcutaneous) and liver lipogenesis rates (estimated using 3H2O and 14C-acetate) were similar in both CETP-Tg and control mice. Lipid retention and glucose uptake by liver, muscle, white and brown adipose tissues (WAT, BAT), estimated after an oral dose of 3H-triolein and 3H-deoxiglucose, respectively, showed no significant differences between groups. In the fed state, CETP group showed higher (~50%) basal lipolysis in vivo and isoproterenol stimulated lipolysis by isolated adipocytes. In accordance, visceral adipose HSL and ATGL mRNA expression were elevated. Beta 3 adrenergic receptor protein levels were upregulated in visceral and brown adipose tissues. Regarding gene expression: UCP1, ATGL, FATP1 were increased in BAT, whilst PPARa, PPARy, PGC1a, HSL, Perilipin, AMPK, CD36, CPT1, RIP140 were not changed. In addition, whole body energy expenditure (measured by respirometry) was found to be elevated in CETP-Tg mice (10%). After fasting, no significant differences were detected in lipolysis and in energy expenditure between groups. These data suggest that CETP could decrease adipose triglycerides availability and change lipolysis and thermogenic related gene expression. The increased whole body energy expenditure results in the reduction of body fat content. These findings disclose a novel anti-adipogenic role for CETP. Key-words: CETP, UCP1, B3AR, lipolysis, adiposity