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/EBPalpha and PPARgamma, 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/EBPalpha and PPARgamma. 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.
Yamakawa
Takahiro
T
Department of Molecular Biology, City of Hope Beckman Research Institute, 1500 E Duarte Road, Duarte, CA 91010, USA.
Sugimoto
Kaori
K
Whitson
Robert H
RH
Itakura
Keiichi
K
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008066:Lipolysis / Q000235:genetics*; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
C503806:Arid5b protein, mouse; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D047495:PPAR gamma; D014157:Transcription Factors; D014280:Triglycerides