title: Common dysregulated pathways in obese adipose tissue and atherosclerosis.
abstract: The metabolic syndrome is becoming increasingly prevalent in the general population that is at simultaneous risk for both type 2 diabetes and cardiovascular disease. The critical pathogenic mechanisms underlying these diseases are obesity-driven insulin resistance and atherosclerosis, respectively. To obtain a better understanding of molecular mechanisms involved in pathogenesis of the metabolic syndrome as a basis for future treatment strategies, studies considering both inherent risks, namely metabolic and cardiovascular, are needed. Hence, the aim of this study was to identify pathways commonly dysregulated in obese adipose tissue and atherosclerotic plaques.
  
  
  
  We carried out a gene set enrichment analysis utilizing data from two microarray experiments with obese white adipose tissue and atherosclerotic aortae as well as respective controls using a combined insulin resistance-atherosclerosis mouse model.
  
  
  
  We identified 22 dysregulated pathways common to both tissues with p values below 0.05, and selected inflammatory response and oxidative phosphorylation pathways from the Hallmark gene set to conduct a deeper evaluation at the single gene level. This analysis provided evidence of a vast overlap in gene expression alterations in obese adipose tissue and atherosclerosis with Il7r, C3ar1, Tlr1, Rgs1 and Semad4d being the highest ranked genes for the inflammatory response pathway and Maob, Bckdha, Aldh6a1, Echs1 and Cox8a for the oxidative phosphorylation pathway.
  
  
  
  In conclusion, this study provides extensive evidence for common pathogenic pathways underlying obesity-driven insulin resistance and atherogenesis which could provide a basis for the development of novel strategies to simultaneously prevent type 2 diabetes and cardiovascular disease in patients with metabolic syndrome.
authors: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: V
authors: V
authors: Moreno-Viedma
authors: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: M
authors: M
authors: Amor
authors: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: A
authors: A
authors: Sarabi
authors: Department of Laboratory Medicine & Core Facility Genomics, Core Facilities, Medical University of Vienna, Vienna, Austria.
authors: M
authors: M
authors: Bilban
authors: AFFiRiS AG, Vienna, Austria.
authors: G
authors: G
authors: Staffler
authors: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Department of Pediatrics and Adolescent Medicine, Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Medical University of Vienna, Vienna, Austria.
authors: M
authors: M
authors: Zeyda
authors: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. thomas.stulnig@meduniwien.ac.at.
authors: T M
authors: TM
authors: Stulnig
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism* / Q000503:physiopathology; D050154:Adiposity / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics* / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D030541:Databases, Genetic; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors
chemical_list: D005819:Genetic Markers
keywords: Atherosclerosis; Cardiovascular diseases; Diabetes mellitus, type 2; Insulin resistance; Pathway analysis