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MiT/TFE Family of Transcription Factors: An Evolutionary Perspective

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Summary: Defective macroautophagy and a failure to initiate the adaptive unfolded protein response in response to ER stress contribute to obesity-associated metabolic dysfunction. The key transcription factor sXBP1 regulates genes involved in lysosomal function in the liver under fasting conditions, and its expression is suppressed in obesity. Hepatic deletion of Xbp1 suppresses the transcription of Tfeb and autophagy, while overexpression of sXbp1 enhances Tfeb transcription and autophagy in mice. The sXBP1-Tfeb signaling pathway has direct functional consequences in the context of obesity.

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