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EFFECTS OF AGE AND OBESITY ON MARKERS OF FIBROSIS IN HEARTS OF C57BL/6J MICE

Abstract

Richard A. Perry, Jr., Lemuel A. Brown, Wesley S. Haynie David E. Lee, Jacob L. Brown, Megan E. Rosa, Nicholas P. Greene, Tyrone A. Washington, University of Arkansas, Fayetteville, Arkansas

In 1990, 23.6% of the elderly population (60+ years old) was obese (≥30 BMI). By 2010, it increased to 39.5%. Aging is typically associated with a reduction in lean mass. Loss of muscle mass with advanced age coupled with increased fat mass is referred to as sarcopenic obesity. Cardiac dysfunction is highly associated with both age and obesity. A contributing, underlying mechanism of cardiac dysfunction is cardiac fibrosis. As the prevalence of obesity in the elderly population continues to rise, a firmer understanding of how age and obesity interact to affect cardiac fibrosis is needed. PURPOSE: To examine how sarcopenic obesity affects markers of fibrosis in cardiac tissue. METHODS: Twenty-four C57BL/6J mice were evenly distributed into either a normal chow (17% kcals from fat) or high-fat (60% kcals from fat) diet after weaning. Twelve mice from each diet were euthanized at 12-16 weeks of age (young). The remaining 12 were sacrificed at 22-24 months of age (aged). The classification of the 4 groups is as follows: young-lean, young-obese, aged-lean, aged-obese (n=6 per group). Whole hearts were excised at time of euthanasia, snap-frozen, and processed for use in gene expression assays. Gene expression was measured using RT-qPCR and normalized to 18s. RESULTS: The aged obese group had a 50% decrease (p<0.05) in the collagen III to I ratio compared to all other groups. The aged obese mice had a two-fold higher TIMP-1 gene content compared to the young obese and aged lean groups (p<0.05). There was a main effect of obesity to increase MMP-2 gene content (p<0.05). There was a main effect of obesity to decrease MMP-9 gene content (p<0.05). CONCLUSION: Elevated collagen III to I ratio has been observed in some forms of end-stage cardiomyopathy. Increased mRNA abundance of TIMP-1 has been shown to be related to cardiac fibrosis and dysfunction. Downregulation of MMP-9 mRNA in conjunction with upregulation of MMP-2 mRNA have been correlated with cardiac pathology and fibrosis, respectively. The tendency for the aged, obese group to display all four of these expressions leads to the conclusion that the aged, obese population is at higher risk of developing cardiac fibrosis, a leading cause of cardiac dysfunction.

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