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  • Title: SREBP-regulated adipocyte lipogenesis is dependent on substrate availability and redox modulation of mTORC1.
    Author: Crewe C, Zhu Y, Paschoal VA, Joffin N, Ghaben AL, Gordillo R, Oh DY, Liang G, Horton JD, Scherer PE.
    Journal: JCI Insight; 2019 Jul 16; 5(15):. PubMed ID: 31310592.
    Abstract:
    The synthesis of lipid and sterol species through de novo lipogenesis (DNL) is regulated by two functionally overlapping but distinct transcription factors: the sterol regulatory element-binding proteins (SREBPs) and carbohydrate response element binding protein (ChREBP). ChREBP is considered to be the dominant regulator of DNL in adipose tissue (AT); however, the SREBPs are highly expressed and robustly regulated in adipocytes, suggesting that the model of AT DNL may be incomplete. Here we describe a new mouse model of inducible, adipocyte-specific overexpression of the insulin-induced gene 1 (Insig1), a negative regulator of SREBP transcriptional activity. Contrary to convention, Insig1 overexpression did block AT lipogenic gene expression. However, this was immediately met with a compensatory mechanism triggered by redox activation of mTORC1 to restore SREBP1 DNL gene expression. Thus, we demonstrate that SREBP1 activity sustains adipocyte lipogenesis, a conclusion that has been elusive due to the constitutive nature of current mouse models.
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