title: The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro.
abstract: The highly regulated differentiation and proliferation of pre-adipocytes play a key role in the initiation of obesity. Fat mass and obesity associated (FTO) is a novel gene strongly associated with the risk of obesity. A deficiency of FTO may cause growth retardation in addition to fat mass and adipocyte size reduction in vivo. To investigate the potential role of Fto gene on the proliferation and differentiation of pre-adipocytes, we generated Fto-knockdown and overexpressed 3T3-L1 cells. Using numerous proliferation assays our results suggest that Fto knockdown leads to suppression of proliferation, lower mitochondrial membrane potential, less cellular ATP, and decreased and smaller intracellular lipid droplets compared with controls (p < 0.05). Western blot analysis demonstrated that Fto knockdown can significantly suppress peroxisome proliferator-activated receptor gamma (PPARγ) and glucose transporter type 4 (GLUT4) expression and inhibit Akt phosphorylation. By contrast, overexpression of Fto had the opposing effect on proliferation, mitochondrial membrane potential, ATP generation, in vitro differentiation, Akt phosphorylation, and PPARγ and GLUT4 expression. Moreover, we demonstrated that Wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, could inhibit phospho-Akt in Fto overexpressed 3T3-L1 cells. Taken together, the results suggest that Fto regulates the proliferation and differentiation of 3T3-L1 cells via multiple mechanisms, including PPARγ and PI3K/Akt signaling.
authors.affiliation: Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou 215123, China. jiaoyang@suda.edu.cn.|Department of Radiation Genetics, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China. jiaoyang@suda.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Radiation Genetics, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China. 15850122119@163.com.
authors.forename: Jingying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Radiation Genetics, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China. llj19900622@163.com.
authors.forename: Lunjie
authors.initials: L
authors.lastname: Lu
authors.affiliation: Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University, Suzhou 215123, China. xujiaying@suda.edu.cn.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Medical College of Soochow University, Suzhou 215123, China. qinliqiang@suda.edu.cn.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Qin
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D051379:Mice; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D007652:Oxo-Acid-Lyases / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051275:Glucose Transporter Type 4; D047495:PPAR gamma; D006899:Mixed Function Oxygenases; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D007652:Oxo-Acid-Lyases
keywords: Fto; differentiation; obesity; pre-adipocyte; proliferation