Proteomic and metabolomic analyses of livers from RagA GTP mice reveal a failed metabolic adaptation to fasting due to a global impairment in PPARĪ± transcriptional program. Herein, we rescue neonatal lethality in RagA GTP mice and find morphometric and metabolic alterations that span glucose, lipid, ketone, bile acid and amino acid homeostasis in adults, and a median lifespan of nine months. We have previously shown that constitutive nutrient signaling to mTORC1 by means of genetic activation of RagA (expression of GTP-locked RagA, or RagA GTP) in mice resulted in a fatal energetic crisis at birth. The mechanistic target of rapamycin complex 1 (mTORC1) integrates cellular nutrient signaling and hormonal cues to control metabolism. Nature Communications volume 12, Article number: 3660 ( 2021) Limited survival and impaired hepatic fasting metabolism in mice with constitutive Rag GTPase signaling
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