Open AccessExpression profiling analysis: Uncoupling protein 2 deficiency improves hepatic glucose, lipid profiles and insulin sensitivity in high‐fat diet‐fed mice by modulating expression of genes in peroxisome proliferator‐activated receptor signaling pathway
Author(s) -
Zhou MeiCen,
Yu Ping,
Sun Qi,
Li YuXiu
Publication year - 2016
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12402
Subject(s) - endocrinology , medicine , peroxisome proliferator activated receptor , lipid metabolism , insulin receptor , peroxisome , biology , insulin resistance , carbohydrate metabolism , signal transduction , uncoupling protein , glucose homeostasis , receptor , glucose transporter , downregulation and upregulation , insulin , lipid droplet , microbiology and biotechnology , gene , biochemistry , adipose tissue , brown adipose tissue
Abstract Aims/Introduction Uncoupling protein 2 ( UCP 2), which was an important mitochondrial inner membrane protein associated with glucose and lipid metabolism, widely expresses in all kinds of tissues including hepatocytes. The present study aimed to explore the impact of UCP 2 deficiency on glucose and lipid metabolism, insulin sensitivity and its effect on the liver‐associated signaling pathway by expression profiling analysis. Materials and Methods Four‐week‐old male UCP 2−/− mice and UCP 2+/+ mice were randomly assigned to four groups: UCP 2−/− on a high‐fat diet, UCP 2−/− on a normal chow diet, UCP 2+/+ on a high‐fat diet and UCP 2+/+ on a normal chow diet. The differentially expressed genes in the four groups on the 16th week were identified by Affymetrix gene array. Results The results of intraperitoneal glucose tolerance test and insulin tolerance showed that blood glucose and β‐cell function were improved in the UCP 2−/− group on high‐fat diet. Enhanced insulin sensitivity was observed in the UCP 2−/− group. The differentially expressed genes were mapped to 23 pathways ( P < 0.05). We concentrated on the ‘peroxisome proliferator‐activated receptor ( PPAR ) signaling pathway’ ( P = 3.19 × 10 −11 ), because it is closely associated with the regulation of glucose and lipid profiles. In the PPAR signaling pathway, seven genes ( PPAR γ , Dbi , Acsl3 , Lpl , Me1 , Scd1 , Fads2 ) in the UCP 2−/− mice were significantly upregulated. Conclusions The present study used gene arrays to show that activity of the PPAR signaling pathway involved in the improvement of glucose and lipid metabolism in the liver of UCP 2‐deficient mice on a long‐term high‐fat diet. The upregulation of genes in the PPAR signaling pathway could explain our finding that UCP 2 deficiency ameliorated insulin sensitivity. The manipulation of UCP 2 protein expression could represent a new strategy for the prevention and treatment of diabetes.