edf壹定发

全体研究组长

郭非凡
博士 研究员 博士生导师

中科院营养代谢与食品安全重点实验室主任

营养相关代谢性疾病发病机理研究课题组组长

研究方向:营养相关代谢性疾病发病机理研究

电子邮件(E-mail ) : ffguo@sibs.ac.cn

电话(Tel) : 021-54920250

邮政编码: 200031

课题组网站: http://www.nutrition.ac.cn/PI_guoff.asp

简历 & 研究方向

2017-至 今 edf壹定发 研究员
2007-2016年 edf壹定发上海生命科学研究院营养科学研究所 研究员
2005-2007年 美国宾州州立大学 生物系 助理研究教授
2002-2005年 美国哈佛大学医学院Beth Israel Deaconess医学中心 博士后
2001-2002年 美国明尼苏达州立大学 精神神经学系 博士后
1997-2001年 日本东京大学 神经生化学系 博士
1992-1995年 大连医科大学 病理生理学系 硕士

研究方向(1000字以内)
营养对于维持机体能量和糖脂代谢稳态至关重要,而营养稳态失衡导致的糖脂代谢紊乱是诱发肥胖、2型糖尿病和脂肪肝等代谢性疾病的重要驱动因素。本课题组长期致力于研究氨基酸的营养感应和对机体的代谢调控机制。前期工作通过利用一种必需氨基酸(亮氨酸)缺乏饮食处理的小鼠模型,发现亮氨酸缺乏导致小鼠体重下降和内脏脂肪显著减少及胰岛素敏感性增强的作用与机理。这些研究结果创新性地将氨基酸与能量和糖脂代谢调节联系在一起,阐释了氨基酸与能量、糖脂代谢之间的关联。但机体各代谢器官如何感应氨基酸改变以及通过哪些具体信号通路来调控能量与糖脂代谢稳态的作用仍不清楚。本课题组拟通过利用多种组织特异性基因敲除小鼠及细胞系体外模型,结合脑室定点注射、尾静脉注射、皮下脂肪组织定点注射腺病毒等手段开展相关研究。这些研究成果将深化人们对氨基酸感应和代谢调控分子机制的理解,阐明各代谢器官调控这些过程的关键信号分子网络,并将有助于发现防治代谢性疾病的新分子药物靶标。

代表性论文(* 通讯编辑)

  1. Hu X, Deng J, Yu T, Chen S, Ge Y, Zhou Z, Guo Y, Ying H, Zhai Q, Chen Y, Yuan F, Niu Y, Shu W, Chen H, Ma C, Liu Z*, Guo F*. ATF4 Deficiency Promotes Intestinal Inflammation in Mice by Reducing Uptake of Glutamine and Expression of Antimicrobial Peptides. Gastroenterology, 2019, 156(4):1098-1111
  2. Xiao F, Guo Y, Deng J, Yuan F, Xiao Y, Hui L, Li Y, Hu Z, Zhou Y, Li K, Han X, Fang Q, Jia W, Chen Y, Ying H, Zhai Q, Chen S, Guo F*. Hepatic c-Jun regulates glucose metabolism via FGF21 and modulates body temperature through the neural signals. Molecular Metabolism, 2019, 20:138-148
  3. Deng Y, Xiao Y, Yuan F, Liu Y, Jiang X, Deng J, Fejes-Toth G, Naray-Fejes-Toth A, Chen S, Chen Y, Ying H, Zhai Q, Shu Y*, Guo F*. SGK1/FOXO3 signaling in hypothalamic POMC neurons mediates glucocorticoid-increased adiposity, Diabetes, 2018, 67(4):569-580
  4. Guo Y, Yu J, Wang C, Li K, Liu B, Du Y, Xiao F, Chen S, Guo F*. miR-212-5p suppresses lipid accumulation by targeting FAS and SCD1, Journal of Molecular Endocrinology, 2017, 59(3):205-217
  5. Xiao Y, Deng Y, Yuan F, Xia T, Liu H, Li Z, Chen S, Liu Z, Ying H, Liu Y, Zhai Q, Guo F*. An ATF4-ATG5 signaling in hypothalamic POMC neurons regulates obesity, Autophagy, 2017, 13(6):1088-1089
  6. Wang L, Pan Y, Huang M, You X, Guo F, Chen Y*. PAQR3 augments amino acid deprivation-induced autophagy by inhibiting mTORC1 signaling, Cellular Signaling, 2017, 33:98-106
  7. He C#, Yu T#, Shi Y, Ma C, Yang W, Fang L, Sun M, Wu W, Xiao F, Guo F, Chen M, Yang H, Qian J, Cong Y, Liu Z*. MicroRNA 301A promotes intestinal inflammation and colitis-associated cancer development by inhibiting BTG1, Gastroenterology, 2017, 152(6):1434-1448
  8. Xiao Y, Deng Y, Yuan F, Xia T, Liu H, Li Z, Liu Z, Ying H, Liu Y, Zhai Q, Chen S, Guo F*. An ATF4/ATG5 signaling in hypothalamic POMC neurons regulates fat mass via affecting energy expenditure, Diabetes, 2017, 66(5):1146-1158
  9. Deng J#, Yuan F#, Guo Y, Xiao Y, Niu Y, Deng Y, Han X, Guan Y, Chen S, Guo F*. Deletion of ATF4 in AgRP neurons promotes fat loss mainly via increasing energy expenditure, Diabetes, 2017, 66(3):640-650
  10. Gong Q, Hu Z, Zhang F, Cui A, Chen X, Jiang H, Gao J, Chen X, Han Y, Liang Q, Ye D, Shi L, Chin YE, Wang Y, Xiao H, Guo F, Liu Y, Zang M, Xu A, Li Y*. Fibroblast growth factor 21 improves hepatic insulin sensitivity by inhibiting mammalian target of rapamycin complex 1 in mice, Hepatology, 2016, 64(2):425-438
  11. Li K#, Xiao Y#, Yu J, Xia T, Liu B, Guo Y, Deng J, Chen S, Wang C, Guo F*. Liver-specific gene inactivation of the transcription factor ATF4 alleviates alcoholic liver steatosis in mice, The Journal of Biological Chemistry, 2016, 291(35):18536-18546
  12. Guo Y#, Yu J#, Deng J, Liu B, Xiao Y, Li K, Xiao F, Yuan F, Liu Y, Chen S, Guo F*. A novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism through peroxisome proliferator–activated receptor alpha, Diabetes, 2016, 65(8):2151-2163
  13. Xiao F#, Deng J#, Guo Y, Niu Y, Yuan F, Yu J, Chen S, Guo F*. BTG1 ameliorates liver steatosis by decreasing stearoyl-CoA desaturase 1 (SCD1) abundance and altering hepatic lipid metabolism, Science Signaling, 2016, 9(428):ra50
  14. Xiao Y#, Liu H#, Yu J, Zhao Z, Xiao F, Xia T, Wang C, Li K, Deng J, Guo Y, Chen S, Chen Y, Guo F*. MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy, Autophagy, 2016, 12(3):592-593
  15. Xiao Y#, Liu H#, Yu J, Zhao Z, Xiao F, Xia T, Wang C, Li K, Deng J, Guo Y, Chen S, Chen Y, Guo F*. Activation of ERK1/2 ameliorates liver steatosis in leptin receptor deficient (db/db) mice via stimulating ATG7-dependent autophagy, Diabetes, 2016, 65(2):393-405
  16. Xiao F, Deng J, Yu J, Guo Y, Chen S, Guo F*. A novel function of B-cell translocation gene 1 (BTG1) in the regulation of hepatic insulin sensitivity in mice via c-Jun, The FASEB Journal, 2016, 30(1):348-359
  17. Li K, Zhang J, Yu J, Liu B, Guo Y, Deng J, Chen S, Wang C*, Guo F*. MicroRNA-214 suppresses gluconeogenesis by targeting activating transcriptional factor 4, The Journal of Biological Chemistry, 2015, 290(13):8185-8195
  18. Xia T#, Zhang Q#, Xiao Y, Wang C, Yu J, Liu H, Liu B, Zhang Y, Chen S, Liu Y, Chen Y, Guo F*. CREB/TRH pathway in the central nervous system regulates energy expenditure in response to deprivation of an essential amino acid, International Journal of Obesity, 2015, 39(1):105-113
  19. Yu J, Xiao F, Guo Y, Deng J, Liu B, Zhang Q, Li K, Wang C, Chen S, Guo F*. Hepatic phosphoserine aminotransferase 1 (PSAT1) regulates insulin sensitivity in mice via tribbles homolog 3 (TRB), Diabetes, 2015, 64(5):1591-1602
  20. Xiao F#, Xia T#, Lv Z#, Zhang Q, Xiao Y, Yu J, Liu H, Deng J, Guo Y, Wang C, Li K, Liu B, Chen S, Guo F*. Central prolactin receptors (PRLRs) regulate hepatic insulin sensitivity in mice via signal transducer and activator of transcription 5 (STAT5) and the vagus nerve, Diabetologia, 2014, 57(10):2136-2144
  21. Xiao F#, Yu J#, Liu B, Guo Y, Li K, Deng J, Zhang J, Wang C, Chen S, Du Y, Lu Y, Xiao Y, Zhang Z, Guo F*. A novel function of MicroRNA 130a-3p in hepatic insulin sensitivity and liver steatosis, Diabetes, 2014, 63(8):2631-2642
  22. Xiao F, Yu J, Guo Y, Deng J, Li K, Du Y, Chen S, Zhu J*, Sheng H*, Guo F*. Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice, Metabolism-Clinical and Experimental, 2014, 63(6):841-850
  23. Yan S, Zhang Q, Zhong X, Tang J, Wang Y, Yu J, Zhou Y, Zhang J, Guo F, Liu Y, FitzGerald GA, Yu Y*. I prostanoid receptor-mediated inflammatory pathway promotes hepatic gluconeogenesis through activation of PKA and inhibition of AKT, Diabetes, 2014, 63(9):2911-2923
  24. Zhang Q, Liu B, Cheng Y, Meng Q, Xia T, Jiang L, Chen S, Liu Y*, Guo F*. Leptin signaling is required for leucine deprivation-enhanced energy expenditure, The Journal of Biological Chemistry, 2014, 289(3):1779-1787
  25. Wang L, Wang X, Li Z, Xia T, Zhu L, Liu B, Zhang Y, Xiao F, Pan Y, Liu Y, Guo F, Chen Y*. PAQR3 has modulatory roles in obesity, energy metabolism and leptin signaling, Endocrinology, 2013, 154(12):4525-4535
  26. Yu J#, Xiao F#, Zhang Q, Liu B, Guo Y, Lv Z, Xia T, Chen S, Li K, Du Y, Guo F*. Prolactin receptor (PRLR) regulates hepatic insulin sensitivity in mice via signal transducer and activator of transcription (STAT)5, Diabetes, 2013, 62(9):3103-3113
  27. Zhang Q, Yu J, Lv Z, Liu B, Xia T, Xiao F, Chen S, Guo F*. Central activating transcription factor (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve, Diabetes, 2013, 62(7):2230-2239
  28. Wang X, Wang L, Zhu L, Pan Y, Xiao F, Liu W, Wang Z, Guo F, Liu Y, Thomas WG, Chen Y*. PAQR3 modulates insulin signaling by shunting phosphoinositide 3-Kinase p110α to the golgi apparatus, Diabetes, 2013, 62(2):444-456
  29. Wang C, Xia T, Du Y, Meng Q, Li H, Liu B, Chen S, Guo F*. Effects of ATF4 on PGC1a expression in brown adipose tissue and metabolic responses to cold stress, Metabolism-Clinical and Experimental, 2013, 62(2):282-289
  30. Xia T, Cheng Y, Zhang Q, Xiao F, Liu B, Chen S, Guo F*. S6K1 in the central nervous system regulates energy expenditure via MC4R/corticotrophin -releasing hormone pathways in response to deprivation of an essential amino acid, Diabetes, 2012, 61(10):2461-2471
  31. Du Y, Meng Q, Zhang Q, Guo F*. Isoleucine or valine deprivation stimulates fat loss via increasing energy expenditure and regulating lipid metabolism in WAT, Amino Acids, 2012, 43(2):725-734
  32. Chen Y*, Lin X, Liu Y, Xie D, Fang J, Le Y, Ke Z, Zhai Q, Wang H, Guo F, Wang F, Liu Y. Research advances at the institute for nutritional sciences at Shanghai, China, Advances in Nutrition, 2011, 2(5): 428-439
  33. Cheng Y#, Zhang Q#, Meng Q, Xia T, Huang Z, Wang C, Liu B, Chen S, Xiao F, Du Y, Guo F*. Leucine deprivation stimulates fat loss via increasing corticotrophin releasing hormone (CRH) expression in the hypothalamus and activating sympathetic nervous system (SNS), Molecular Endocrinology, 2011, 25(9):1624-1635
  34. Xiao F, Huang Z, Li H, Yu J, Wang C, Chen S, Meng Q, Cheng Y, Gao X, Li J, Liu Y, Guo F*. Leucine deprivation increases hepatic insulin sensitivity via GCN2/mTOR/S6K1 and AMPK pathways, Diabetes, 2011, 60(3):746-756
  35. Zhang Q, Li H, Guo F*. Amygdala, an important regulator for food intake (INVITED Review), Frontier in Biology, 2011, 6:82-85
  36. Cheng Y#, Meng Q#, Wang C, Li H, Huang Z, Chen S, Xiao F, Guo F*. Leucine deprivation decreases fat mass by stimulation of lipolysis in WAT and upregulation of UCP1 in BAT, Diabetes, 2010, 59(1):17-25
  37. Wang C, Huang Z, Du Y, Cheng Y, Chen S, Guo F*. ATF4 regulates lipid metabolism and thermogenesis, Cell Research, 2010, 20(2):174-184
  38. Guo F, Cavener D*. The GCN2 eIF2α kinase regulates fatty-acid homeostasis in the liver during deprivation of an essential amino acid, Cell Metabolism, 2007, 5(2):103-114
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