Influence of diet on visceral adipose remodeling in NONcNZO10 mice with polygenic susceptibility for type 2 diabetes

Nikhil C. Adi, Jennipher N. Adi, Liliana Cesar, Arthur S. Agatston, Paul Kurlansky, Keith A Webster

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2142-2146
Number of pages5
JournalObesity
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2012

Fingerprint

Type 2 Diabetes Mellitus
Diet
Intra-Abdominal Fat
Vascular Endothelial Growth Factor C
Fish Oils
Vascular Endothelial Growth Factor A
Extracellular Matrix
Analysis of Variance
Fats
Body Weight
Insulin
Tissue Expansion
Genes
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase 3
Peroxisome Proliferator-Activated Receptors
Proteins
Matrix Metalloproteinase 2
Hyperinsulinism
von Willebrand Factor

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Adi, N. C., Adi, J. N., Cesar, L., Agatston, A. S., Kurlansky, P., & Webster, K. A. (2012). Influence of diet on visceral adipose remodeling in NONcNZO10 mice with polygenic susceptibility for type 2 diabetes. Obesity, 20(10), 2142-2146. https://doi.org/10.1038/oby.2012.167

Influence of diet on visceral adipose remodeling in NONcNZO10 mice with polygenic susceptibility for type 2 diabetes. / Adi, Nikhil C.; Adi, Jennipher N.; Cesar, Liliana; Agatston, Arthur S.; Kurlansky, Paul; Webster, Keith A.

In: Obesity, Vol. 20, No. 10, 01.10.2012, p. 2142-2146.

Research output: Contribution to journalArticle

Adi, NC, Adi, JN, Cesar, L, Agatston, AS, Kurlansky, P & Webster, KA 2012, 'Influence of diet on visceral adipose remodeling in NONcNZO10 mice with polygenic susceptibility for type 2 diabetes', Obesity, vol. 20, no. 10, pp. 2142-2146. https://doi.org/10.1038/oby.2012.167
Adi, Nikhil C. ; Adi, Jennipher N. ; Cesar, Liliana ; Agatston, Arthur S. ; Kurlansky, Paul ; Webster, Keith A. / Influence of diet on visceral adipose remodeling in NONcNZO10 mice with polygenic susceptibility for type 2 diabetes. In: Obesity. 2012 ; Vol. 20, No. 10. pp. 2142-2146.
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