PMID- 27418549 OWN - NLM STAT- MEDLINE DCOM- 20170516 LR - 20180820 IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 186 IP - 8 DP - 2016 Aug TI - Gastric Bypass Surgery Reverses Diabetic Phenotypes in Bdnf-Deficient Mice. PG - 2117-2128 LID - S0002-9440(16)30122-5 [pii] LID - 10.1016/j.ajpath.2016.04.009 [doi] AB - 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-alpha 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. CI - Copyright (c) 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. FAU - Jiang, Shujun AU - Jiang S AD - 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. FAU - Wang, Qinghua AU - Wang Q AD - 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. FAU - Huang, Zan AU - Huang Z AD - Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China. FAU - Song, Anying AU - Song A AD - 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. FAU - Peng, Yu AU - Peng Y AD - Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China. FAU - Hou, Siyuan AU - Hou S AD - 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. FAU - Guo, Shiying AU - Guo S AD - 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. FAU - Zhu, Weiyun AU - Zhu W AD - Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China. FAU - Yan, Sheng AU - Yan S AD - First Hospital of Zhejiang Province, First Affiliate Hospital, Zhejiang University, Hangzhou, China. FAU - Lin, Zhaoyu AU - Lin Z AD - 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. FAU - Gao, Xiang AU - Gao X AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160711 PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*deficiency MH - Diabetes Mellitus, Experimental/*surgery MH - Diabetes Mellitus, Type 2/*surgery MH - Disease Models, Animal MH - *Gastric Bypass MH - *Gastrointestinal Microbiome MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Real-Time Polymerase Chain Reaction EDAT- 2016/07/16 06:00 MHDA- 2017/05/17 06:00 CRDT- 2016/07/16 06:00 PHST- 2015/10/07 00:00 [received] PHST- 2016/04/01 00:00 [revised] PHST- 2016/04/11 00:00 [accepted] PHST- 2016/07/16 06:00 [entrez] PHST- 2016/07/16 06:00 [pubmed] PHST- 2017/05/17 06:00 [medline] AID - S0002-9440(16)30122-5 [pii] AID - 10.1016/j.ajpath.2016.04.009 [doi] PST - ppublish SO - Am J Pathol. 2016 Aug;186(8):2117-2128. doi: 10.1016/j.ajpath.2016.04.009. Epub 2016 Jul 11.