Gastric Bypass Surgery Reverses Diabetic Phenotypes in Bdnf-Deficient Mice

Shujun Jiang; Qinghua Wang; Zan Huang; Anying Song; Yu Peng; Siyuan Hou; Shiying Guo; Weiyun Zhu; Sheng Yan; Zhaoyu Lin; Xiang Gao

doi:10.1016/j.ajpath.2016.04.009

Gastric Bypass Surgery Reverses Diabetic Phenotypes in Bdnf-Deficient Mice

Am J Pathol. 2016 Aug;186(8):2117-2128. doi: 10.1016/j.ajpath.2016.04.009. Epub 2016 Jul 11.

Authors

Shujun Jiang¹, Qinghua Wang², Zan Huang³, Anying Song¹, Yu Peng³, Siyuan Hou¹, Shiying Guo¹, Weiyun Zhu³, Sheng Yan⁴, Zhaoyu Lin⁵, Xiang Gao⁶

Affiliations

¹ 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.
² 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.
³ Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China.
⁴ First Hospital of Zhejiang Province, First Affiliate Hospital, Zhejiang University, Hangzhou, China.
⁵ 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.
⁶ 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.

PMID: 27418549
DOI: 10.1016/j.ajpath.2016.04.009

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western
Brain-Derived Neurotrophic Factor / deficiency*
Diabetes Mellitus, Experimental / surgery*
Diabetes Mellitus, Type 2 / surgery*
Disease Models, Animal
Gastric Bypass*
Gastrointestinal Microbiome*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Real-Time Polymerase Chain Reaction

Substances

Brain-Derived Neurotrophic Factor