title: Gastric Bypass Surgery Reverses Diabetic Phenotypes in Bdnf-Deficient Mice.
abstract: Duodenum-jejunum gastric bypass (DJB) has been used to treat morbid diabetic patients. However, neither the suitability among patients nor the mechanisms of this surgical treatment is clear. Previously, we reported a new mouse strain named Timo as type 2 diabetes model caused by brain-derived neurotrophic factor (Bdnf) deficiency. In this study, we found that DJB on Timo mice reversed their metabolic abnormalities without altering the expression of Bdnf. Glucose tolerance and insulin sensitivity were improved greatly, along with reduction of fat accumulation in liver and white adipose tissue. The gut flora population was altered by DJB with increased proportion of Firmicutes and decreased Actinobacteria and Proteobacteria in the ileum after surgery. Systemic inflammation in Timo mice was greatly suppressed with less macrophage infiltration and lower tumor necrosis factor-α levels in liver and white adipose tissue after surgery. Interestingly, the alteration of gut microflora abundance and improved metabolism preceded the inflammation alleviation after DJB surgery. These results suggested that DJB can reverse Bdnf deficiency-associated metabolic abnormality. In addition, the reduced inflammation may not be the initial cause for the DJB-associated metabolic and microbiota alterations. The increased BDNF protein levels in hypothalamus and hippocampus may result from microbiota change after DJB surgery.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China; Laboratory Animal Center, Nantong University, Nantong, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
authors.forename: Anying
authors.initials: A
authors.lastname: Song
authors.affiliation: Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Guo
authors.affiliation: Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Zhu
authors.affiliation: First Hospital of Zhejiang Province, First Affiliate Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China; Collaborative Innovation Center of Genetics and Development, Nanjing University, Nanjing, China. Electronic address: linzy@nju.edu.cn.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China; Collaborative Innovation Center of Genetics and Development, Nanjing University, Nanjing, China. Electronic address: gaoxiang@nju.edu.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency*; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000601:surgery*; D004195:Disease Models, Animal; D015390:Gastric Bypass; D000069196:Gastrointestinal Microbiome; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D019208:Brain-Derived Neurotrophic Factor