A Novel Dual Eigen-Analysis of Mouse Multi-Tissues' Expression Profiles Unveils New Perspectives into Type 2 Diabetes

作者

Li, LM;Liu, XX;Wang, L;Wang, Y;Liu, XQ;Tian, X;Gong, FZ;Shen, L;Peng, XD

作者单位

[Li, Lei M.; Wang, Lin; Wang, Yong; Liu, Xiuqin; Tian, Xue; Gong, Fuzhou] Chinese Acad Sci, Acad Math & Syst Sci, Natl Ctr Math & Interdisciplinary Sci, Beijing 100190, Peoples R China.;-;[Li, Lei M.; Gong, Fuzhou] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.;-;[Liu, Xiuxiu; Shen, Li] Peking Univ, Dept Cell Biol, Hlth Sci Ctr, Beijing 100191, Peoples R China.;-;[Liu, Xiuxiu] Shandong Univ, Dept Otorhinolaryngol Head & Neck Surg, Shandong Prov Key Lab Otol, Shandong Prov Hosp, Jinan 250021, Peoples R China.;-;[Wang, Lin] Capital Univ Econ & Business, Sch Stat, Beijing, Peoples R China.;-;[Liu, Xiuqin] Univ Sci & Technol Beijing, Sch Math & Phys, Beijing, Peoples R China.;-;[Peng, Xiao-ding] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.

摘要

Type 2 diabetes (T2D) is a complex and polygenic disease yet in need of a complete picture of its development mechanisms. To better understand the mechanisms, we examined gene expression profiles of multi-tissues from outbred mice fed with a high-fat diet (HFD) or regular chow at weeks 1, 9, and 18. To analyze such complex data, we proposed a novel dual eigen-analysis, in which the sample-and gene-eigenvectors correspond respectively to the macro-and micro-biology information. The dual eigen-analysis identified the HFD eigenvectors as well as the endogenous eigenvectors for each tissue. The results imply that HFD influences the hepatic function or the pancreatic development as an exogenous factor, while in adipose HFD's impact roughly coincides with the endogenous eigenvector driven by aging. The enrichment analysis of the eigenvectors revealed diverse HFD impact on the three tissues over time. The diversity includes: inflammation, degradation of branched chain amino acids (BCAA), and regulation of peroxisome proliferator activated receptor gamma (PPAR gamma). We reported that in the pancreas remarkable up-regulation of angiogenesis as downstream of the HIF signaling pathway precedes hyperinsulinemia. The dual eigen-analysis and discoveries provide new evaluations/guidance in T2D prevention and therapy, and will also promote new thinking in biology and medicine.

关键词

CHAIN AMINO-ACIDS; INSULIN-RESISTANCE; DIFFERENTIATION; INFLAMMATION; KEGG; NORMALIZATION; MACROPHAGES; CAVEOLIN-1; INDUCTION; PATHWAYS

基本信息

所属机构:

归属医师:

PMID：28698587

UT：000405172600011

刊名:SCIENTIFIC REPORTS

年，卷(期):2017年7卷

DOI：10.1038/s41598-017-05405-x

附件： pdf

收录: SCIE