Home > Browse Issues > Vol.37 No.9
The Role of CRTC2 in Hepatic Lipid Homeostasis
Han Jinbo1#, Li Erwei1#, Chen Liqun1, Zhang Yuanyuan1, Wei Fangchao1, Liu Jieyuan2, Deng Haiteng2, Wang Yiguo1*
1Ministry of Education Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
2Center of Biommedical Analysis, School of Life Sciences, Tsinghua University, Beijing 100084, China
2Center of Biommedical Analysis, School of Life Sciences, Tsinghua University, Beijing 100084, China
Abstract: Abnormal accumulation of triglycerides in the liver， caused in part by increased de novo lipogenesis， results in nonalcoholic fatty liver disease and insulin resistance. Sterol regulatory element-binding protein 1 (SREBP1)， a master transcriptional regulator of lipogenesis， is synthesized as an inactive precursor bound to the endoplasmic reticulum. Upon sensing to insulin stimulation or sterol depletion， SREBP1 is transported to the Golgi through coat protein complex II (COPII)-mediated vesicle trafficking， released by a two-step proteolytic cleavage and then shuttled to the nucleus to induce the expression of genes involved in cholesterol and fatty acid synthesis. However， the mechanisms underlying enhanced SREBP1 activity in insulin-resistant obesity and diabetes remain unclear. Here we show that CREB regulated transcription coactivator 2 (CRTC2) functions as a mediator of mechanistic target of rapamycin (mTOR) signaling to modulate COPII-dependent SREBP1 processing and lipid homeostasis in the fed state and in obesity.
CN
EN