title: Expression 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.
abstract: OBJECTIVE
  Uncoupling protein 2 (UCP2), 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 UCP2 deficiency on glucose and lipid metabolism, insulin sensitivity and its effect on the liver-associated signaling pathway by expression profiling analysis.
  
  
  METHODS
  Four-week-old male UCP2-/- mice and UCP2+/+ mice were randomly assigned to four groups: UCP2-/- on a high-fat diet, UCP2-/- on a normal chow diet, UCP2+/+ on a high-fat diet and UCP2+/+ 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 UCP2-/- group on high-fat diet. Enhanced insulin sensitivity was observed in the UCP2-/- 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 (PPARγ, Dbi, Acsl3, Lpl, Me1, Scd1, Fads2) in the UCP2-/- 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 UCP2-deficient mice on a long-term high-fat diet. The upregulation of genes in the PPAR signaling pathway could explain our finding that UCP2 deficiency ameliorated insulin sensitivity. The manipulation of UCP2 protein expression could represent a new strategy for the prevention and treatment of diabetes.
authors.affiliation: Department of Endocrinology Key Laboratory of Endocrinology Ministry of Health Peking Union Medical College Hospital Beijing China.
authors.forename: Mei-Cen
authors.initials: MC
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy the Third People's Hospital Qinhuangdao China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Endocrinology Key Laboratory of Endocrinology Ministry of Health Peking Union Medical College Hospital Beijing China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Endocrinology Key Laboratory of Endocrinology Ministry of Health Peking Union Medical College Hospital Beijing China.
authors.forename: Yu-Xiu
authors.initials: YX
authors.lastname: Li
mesh_terms: D000818:Animals; D001786:Blood Glucose; D059305:Diet, High-Fat; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011897:Random Allocation; D015398:Signal Transduction; D000071246:Uncoupling Protein 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D047492:Peroxisome Proliferator-Activated Receptors; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D005947:Glucose
keywords: Glucose and lipid metabolism; Peroxisome proliferator‐activated receptor signaling pathway; Uncoupling protein 2