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>Tfe3 and Tfeb Transcriptionally Regulate Peroxisome Proliferator-Activated Receptor gamma 2 Expression in Adipocytes and Mediate Adiponectin and Glucose Levels in Mice
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Tfe3 and Tfeb Transcriptionally Regulate Peroxisome Proliferator-Activated Receptor gamma 2 Expression in Adipocytes and Mediate Adiponectin and Glucose Levels in Mice
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机译：Tfe3 and Tfeb Transcriptionally Regulate Peroxisome Proliferator-Activated Receptor gamma 2 Expression in Adipocytes and Mediate Adiponectin and Glucose Levels in Mice
Members of the MiT transcription factor family are pivotal regulators of several lineage-selective differentiation programs. We show that two of these, Tfeb and Tfe3, control the regulator of adipogenesis, peroxisome proliferator-activated receptor gamma 2 (Ppar gamma 2). Knockdown of Tfeb or Tfe3 expression during in vitro adipogenesis causes dramatic downregulation of Ppar gamma 2 expression as well as adipogenesis. Additionally, we found that these factors regulate Ppar gamma 2 in mature adipocytes. Next, we demonstrated that Tfeb and Tfe3 act directly by binding to consensus E-boxes within the Ppar gamma transcriptional regulatory region. This transcriptional control also exists in vivo, as we discovered that wild-type mice in the fed state increased their expression of Tfe3, Tf3b, and Ppar gamma in white adipose tissue. Furthermore, Tfe3 knockout (Tfe3KO) mice in the fed state failed to upregulate Ppar gamma and the adiponectin gene, a Ppar gamma-dependent gene, confirming the in vivo role for Tfe3. Lastly, we found that blood glucose is elevated and serum adiponectin levels are suppressed in the Tfe3KO mice, indicating that the Tfe3/Tfeb/Ppar gamma 2 axis may contribute to whole-body energy balance. Thus, we offer new insights into the upstream regulation of Ppar gamma by Tfe3/Tf3b and propose that targeting these transcription factors may offer opportunities to complement existing approaches for the treatment of diseases that have dysregulated energy metabolism.
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