Mice lacking modulator recognition factor-2 (Mrf-2, ARID5B) have less far in brown and white adipose tissues, partly because of a defect in adipocyte differentiation We have also shown that knockdown of Mrf-2 decreases the expression of the adipogenic transcription factors C/EBP alpha and PPAR gamma, and inhibits adipogenesis in 3T3-L1 preadipocytes Since these transcription factors may also contribute to the maintenance of adipocyte function, we examined the effects of siRNA targeted to Mrf-2 on triglyceride metabolism in mature 3T3-L1-derived adipocytes As it did in differentiating adipocytes. knockdown of Mrf-2 decreased the expression of both C/EBP alpha and PPAR gamma. Knockdown of Mrf-2 also activated both lipolysis and triglyceride synthesis, and caused a significant increase in the ratio of glycerol release to free fatty acid release. This suggests that knockdown of Mrf-2 increases the rate of fatty acid recycling in 3T3-L1-derived adipocytes Continual cycling of fatty acids through lipolysis and triglyceride Synthesis could lead to dissipation of energy. Therefore. the activation of such a futile cycle via the suppression of Mrf-2 Could be an effective treatment for obesity and diabetes (c) 2009 Elsevier Inc All rights reserved.