title: NYGGF4 as a new therapeutic target for obesity-associated insulin resistance.
abstract: Obesity-associated insulin resistance (IR) is manifested by increased hepatic glucose output and reduced glucose disposal in the peripheral tissues at a given level of insulin. Genetic factors play an important role in the development of obesity-associated IR. We identified a new cDNA by using suppression subtractive hybridization (SSH), which was expressed at a higher level in obese subjects and named NYGGF4. We found that the increased expression of NYGGF4 led to a reduction in insulin-stimulated glucose uptake and impaired insulin-stimulated glucose transport in mature adipocytes. We therefore propose the hypothesis that NYGGF4 may be a new therapeutic target for obesity-associated IR. NYGGF4 acts directly on the IRS1/PI3K/AKT insulin pathway to reduce glucose uptake and transport, impairs mitochondrial function and causes IR, which supports our hypothesis that NYGGF4 may be a useful therapeutic target for obesity-associated IR. However, its usefulness as a new therapeutic target need to be confirmed by further investigations, including NYGGF4 knockout mice models, which will be used to validate the role of NYGGF4 in vivo. Future studies are also required to determine whether downregulated expression of NYGGF4 contributes to these therapeutic actions.
authors.affiliation: Department of Pediatrics, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing, Jiangsu 210004, PR China.
authors.forename: Zhangbin
authors.initials: Z
authors.lastname: Yu
authors.forename: Xirong
authors.initials: X
authors.lastname: Guo
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000627:therapeutic use; D018076:DNA, Complementary / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D009765:Obesity / Q000150:complications*
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; C514653:PID1 protein, human; D005947:Glucose