title: Hepatic Phosphoserine Aminotransferase 1 Regulates Insulin Sensitivity in Mice via Tribbles Homolog 3.
abstract: Phosphoserine aminotransferase 1 (PSAT1) is an enzyme participating in serine synthesis. A role of PSAT1 in the regulation of insulin sensitivity, however, is unknown. In this study, we showed that hepatic PSAT1 expression and liver serine levels are reduced in genetically engineered leptin receptor-deficient (db/db) mice and high-fat diet (HFD)-induced diabetic mice. Additionally, overexpression of PSAT1 by adenovirus expressing PSAT1 improved insulin signaling and insulin sensitivity in vitro and in vivo under normal conditions. Opposite effects were observed when PSAT1 was knocked down by adenovirus expressing small hairpin RNA specific for PSAT1 (Ad-shPSAT1). Importantly, overexpression of PSAT1 also significantly ameliorated insulin resistance in diabetic mice. In addition, PSAT1 inhibited the expression of hepatic tribbles homolog 3 (TRB3) in vitro and in vivo, and adenoviruses expressing small hairpin RNA against TRB3-mediated inhibition of TRB3 reversed the attenuated insulin sensitivity in Ad-shPSAT1 mice. Interestingly, we found that serine mediates PSAT1 regulation of TRB3 expression and insulin signaling in vitro. These results identify a novel function for hepatic PSAT1 in regulating insulin sensitivity and provide important insights in targeting PSAT1 for treating insulin resistance and type 2 diabetes. Our results also suggest that nonessential amino acid serine may play an important role in regulating insulin sensitivity.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Deng
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Shanghai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China ffguo@sibs.ac.cn.
authors.forename: Feifan
authors.initials: F
authors.lastname: Guo
mesh_terms: D000818:Animals; D001786:Blood Glucose; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004041:Dietary Fats / Q000009:adverse effects; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D005951:Glucose Tolerance Test; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D000637:Transaminases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D018797:Cell Cycle Proteins; D004041:Dietary Fats; D007328:Insulin; C474830:TRB3 protein, mouse; D000637:Transaminases; C022393:phosphoserine aminotransferase