Abstract
We previously identified Drosophila REPTOR and REPTOR-BP as transcription factors downstream of mTORC1 that play an important role in regulating organismal metabolism. We study here the mammalian ortholog of REPTOR-BP, Crebl2. We find that Crebl2 mediates part of the transcriptional induction caused by mTORC1 inhibition. In C2C12 myoblasts, Crebl2 knockdown leads to elevated glucose uptake, elevated glycolysis as observed by lactate secretion, and elevated triglyceride biosynthesis. In Hepa1-6 hepatoma cells, Crebl2 knockdown also leads to elevated triglyceride levels. In sum, this works identifies Crebl2 as a regulator of cellular metabolism that can link nutrient sensing via mTORC1 to the metabolic response of cells.
Highlights
We previously identified Drosophila REPTOR and REPTOR-BP as transcription factors downstream of mTORC1 that play an important role in regulating organismal metabolism
We identified two such cAMP response element binding protein (CREB)-like factors REPTOR (CG13624) and REPTOR-BP (CG18619) as transcription factors downstream of mTORC1 that play an important role in regulating metabolism in Drosophila[14]
We find that loss of Crebl[2] has strong consequences on cellular metabolism in both myocytes and hepatocytes, where it regulates glucose uptake and lipid accumulation
Summary
We previously identified Drosophila REPTOR and REPTOR-BP as transcription factors downstream of mTORC1 that play an important role in regulating organismal metabolism. In Hepa[1,2,3,4,5,6] hepatoma cells, Crebl[2] knockdown leads to elevated triglyceride levels This works identifies Crebl[2] as a regulator of cellular metabolism that can link nutrient sensing via mTORC1 to the metabolic response of cells. Since metabolic pathways are highly complex networks of enzymes with many components, their regulation is often controlled by transcription factors that have the potential to activate or repress multiple genes at the same time One of those transcription factors is cAMP response element binding protein (CREB)[1]. We identified two such CREB-like factors REPTOR (CG13624) and REPTOR-BP (CG18619) as transcription factors downstream of mTORC1 that play an important role in regulating metabolism in Drosophila[14]. This work identifies Crebl[2] as a regulator of cellular metabolism and suggests that Crebl[2] knockout mice would be worth studying in the future
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