title: Influence of diet on visceral adipose remodeling in NONcNZO10 mice with polygenic susceptibility for type 2 diabetes.
abstract: Visceral adipose tissue (VAT) is a source of inflammatory cytokines that in obese subjects may contribute to low-level systemic inflammation and development of metabolic syndrome. Expansion of VAT involves adipocyte hyperplasia and hypertrophy and requires breakdown of the extracellular matrix and increased vascular outgrowth. To investigate changes of gene expression associated with VAT expansion and the role of combined genetics and diet, we implemented gene microarray analyses of VAT in NONcNZO10 (NZ10) and control SWR/J mice subjected to control chow (CD) or a diet of high protein and fish oil (HPO). NZ10 mice on CD showed increased body weight, hyperglycemia, and hyperinsulinemia at 25 weeks whereas those on HPO diet retained normal insulin levels and were normoglycemic. Two-way ANOVA revealed a significant interaction between diet and strain on blood glucose, serum insulin, and percent fat but not for body weight. Microarray heat maps revealed a remarkable combined effect of genetics and diet on genes that regulate extracellular matrix as well as angiogenic genes. Real time-PCR (RT-PCR) confirmed markedly increased expression of matrix metalloproteinases (MMPs) 2, 3, 11, and 12, vascular endothelial growth factor-A and C (VEGF-A and C), Von Willebrand Factor, and peroxisome proliferator-activated receptor-γ (PPAR-γ) selectively in the NZ10/CD group. MMP7 was significantly decreased. Protein levels of MMP2, 3, and 9 were significantly increased in the VA of NZ10 mice fed CD while those of MMP7 were downregulated. Microarrays also revealed diet-dependent two to fourfold increased expression of all four tissue inhibitor of metalloproteinases (TIMP) isoforms in NZ10 mice. Two-way ANOVA confirmed strongly interactive roles of diet and genetics on fat deposition and progression of type 2 diabetes in this polygenic mouse model.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, Florida, USA.
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Adi
authors.forename: Jennipher N
authors.initials: JN
authors.lastname: Adi
authors.forename: Liliana
authors.initials: L
authors.lastname: Cesar
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Agatston
authors.forename: Paul
authors.initials: P
authors.lastname: Kurlansky
authors.forename: Keith A
authors.initials: KA
authors.lastname: Webster
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D004041:Dietary Fats / Q000494:pharmacology*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood; D051379:Mice; D008808:Mice, Inbred CBA; D046228:Microarray Analysis; D009765:Obesity / Q000097:blood / Q000235:genetics*; D047495:PPAR gamma / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D015430:Weight Gain; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D047495:PPAR gamma; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D020782:Matrix Metalloproteinases