Modulator recognition factor-2 regulates triglyceride metabolism in adipocytes

Mice lacking modulator recognition factor-2 (Mrf-2; ARID5B) have less fat 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/EBPα and PPARγ, 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/EBPα and PPARγ. 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.